First in Human Study of M4344 in Participants With Advanc... | NCT02278250 | Trialant
NCT02278250
Sponsor
EMD Serono Research & Development Institute, Inc.
Status
Completed
Last Update Posted
Mar 16, 2023Actual
Enrollment
97Actual
Phase
Phase 1
Conditions
Solid Tumor
Advanced Solid Tumor
Interventions
M4344 10 mg BIW
M4344 20 mg BIW
M4344 40 mg BIW
M4344 80 mg BIW
M4344 160 mg BIW
M4344 300 mg BIW
M4344 450 mg BIW
M4344 700 mg BIW
M4344 1050 mg BIW
M4344 1200 mg BIW
M4344 100 mg BID
M4344 150 mg QD
M4344 250 mg QD
M4344 350 mg QD
M4344 400 mg
M4344 500 mg
Carboplatin
Countries
United States
Netherlands
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02278250
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
MS201922-0001
Secondary IDs
ID
Type
Description
Link
VX14-803-001
Other Identifier
Other
2014-003838-86
EudraCT Number
Brief Title
First in Human Study of M4344 in Participants With Advanced Solid Tumors
Official Title
An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of M4344 (Formerly VX-803) as a Single Agent and in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors
Acronym
Not provided
Organization
EMD SeronoINDUSTRY
Status Module
Record Verification Date
Mar 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 26, 2015Actual
Primary Completion Date
Jun 16, 2021Actual
Completion Date
Sep 24, 2021Actual
First Submitted Date
Oct 27, 2014
First Submission Date that Met QC Criteria
Oct 27, 2014
First Posted Date
Oct 29, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
May 24, 2022
Results First Submitted that Met QC Criteria
Mar 14, 2023
Results First Posted Date
Mar 16, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 14, 2023
Last Update Posted Date
Mar 16, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
EMD Serono Research & Development Institute, Inc.INDUSTRY
Collaborators
Name
Class
Merck KGaA, Darmstadt, Germany
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study was to evaluate the safety and tolerability of multiple ascending doses of single-agent M4344 administered twice-weekly (BIW), twice daily (BID) or once daily dose schedule in participants with advanced solid tumors. This investigation is a three part study examining M4344 alone and in combination with carboplatin to determine the safety and maximum tolerated dose.
Detailed Description
Not provided
Conditions Module
Conditions
Solid Tumor
Advanced Solid Tumor
Keywords
VX14-803-001
VX-803
M4344
Advanced Solid Tumor
Cytotoxic Chemotherapy
Carboplatin
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
97Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part A: M4344 10 mg BIW
Experimental
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 10 mg BIW
Part A: M4344 20 mg BIW
Experimental
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 20 mg BIW
Part A: M4344 40 mg BIW
Experimental
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 40 mg BIW
Part A: M4344 80 mg BIW
Experimental
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 80 mg BIW
Part A: M4344 160 mg BIW
Experimental
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
M4344 10 mg BIW
Drug
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.
up to safety follow-up visit (Week 124.9)
Part A: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0)
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v4.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
up to safety follow-up visit (Week 124.9)
Part A: Number of Participants With Clinically Relevant Findings in Vital Signs
Secondary Outcomes
Measure
Description
Time Frame
Part A: Maximum Observed Plasma Concentration (Cmax) of M4344
Cmax was obtained directly from the plasma concentration versus time curve.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Part A, A2 and A3: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit
Part B1: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit and/or participants must have progressed after at least 1 prior chemotherapy regimen in the metastatic setting, and for which carboplatin would be considered standard of care.
Part C: Participants with 1 histologically or cytologically confirmed malignant advanced solid tumors for which no recommended standard therapy is available (that is, participants who have exhausted all standard of care options according to National Comprehensive Cancer Network [NCCN] Guidance) which may convey clinical benefit, and whose tumor has at least 1 of the following biomarkers as determined by a central trial assay or by an assay with appropriate regulatory status: - C1 or C4: loss-of-function mutations in the gene ARID1A - C2 or C5: loss-of-function mutations in the genes ATRX and/or DAXX - C3 or C6: loss-of-function mutation in the gene ataxia telangiectasia mutated (ATM) - This mandatory biomarker assessment must be conducted during screening on a fresh tumor biopsy (or a biopsy obtained after the end of the previous treatment regimen). If this is not possible for medical reason(s), available archival tumor material can be used (historical data should not be used to confirm biomarker status)
Measurable disease either according to RECIST criteria (Version 1.1)
WHO performance status of 0 or 1
Life expectancy of greater than or equal to (>=)12 weeks
Hematological and biochemical indices within acceptable ranges at Screening
Other protocol defined inclusion criteria could apply
Exclusion Criteria:
Radiotherapy, unless brief course for palliative therapy, endocrine therapy, target-specific therapy, immunotherapy, or chemotherapy during the 4 weeks (6 weeks for nitrosoureas and Mitomycin-C, and 4 weeks for investigational medicinal products) or 4 drug half-lives before first dose of study drug, whichever is greater
Part B1: More than 6 cycles of prior therapy with carboplatin
Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the investigator should not exclude the participant
Part B1: Any known history of Grade 4 thrombocytopenia with any prior chemotherapy regimen
Brain metastases unless asymptomatic, treated, stable, and not requiring steroids for at least 4 weeks before first dose of study drug
Female participants who are already pregnant or lactating, or plan to become pregnant within 6 months of the last dose of study drug are excluded. Female participants of childbearing potential must adhere to contraception guidelines. Female participants will be considered to be of nonchildbearing potential if they have undergone surgical hysterectomy or bilateral oophorectomy or have been amenorrheic for over 2 years with a screening serum follicle-stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females.
Male participants with partners of childbearing potential must agree to adhere to contraception guidelines. Men with pregnant or lactating partners or partners who plan to become pregnant during the study or within 6 months of the last dose of study drug are excluded.
Major surgery less than or equal to (<=) 4 weeks before first dose of study drug or incomplete recovery from a prior major surgical procedure
Serious co-morbid medical conditions, including clinically-significant cardiac disease
Other protocol defined exclusion criteria could apply
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Medical Responsible
EMD Serono Research & Development Institute, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
University of Michigan Comprehensive Cancer Center
Jo U, Senatorov IS, Zimmermann A, Saha LK, Murai Y, Kim SH, Rajapakse VN, Elloumi F, Takahashi N, Schultz CW, Thomas A, Zenke FT, Pommier Y. Novel and Highly Potent ATR Inhibitor M4344 Kills Cancer Cells With Replication Stress, and Enhances the Chemotherapeutic Activity of Widely Used DNA Damaging Agents. Mol Cancer Ther. 2021 Aug;20(8):1431-1441. doi: 10.1158/1535-7163.MCT-20-1026. Epub 2021 May 27.
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
This study was planned to be conducted in multiple parts; Part A, Part A2, Part B1, Part A3 (Dose escalation), Part C1, Part C2, Part C3, Part C4, Part C5 and Part C6 (Dose expansion). On 10 December 2020, the Sponsor decided to discontinue the development of M4344 and stop enrollment of any new participants. Due to the low number of cohorts and participants, data were not summarized per Part (Part C1, C2 and C3). Also, optional Parts A3, C4, C5, and C6 were not conducted.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG001
Part A: M4344 20 mg BIW
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jan 29, 2020
May 24, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: M4344 160 mg BIW
Part A: M4344 300 mg BIW
Experimental
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 300 mg BIW
Part A: M4344 450 mg BIW
Experimental
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 450 mg BIW
Part A: M4344 700 mg BIW
Experimental
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 700 mg BIW
Part A: M4344 1050 mg BIW
Experimental
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 1050 mg BIW
Part A: M4344 1200 mg BIW
Experimental
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 1200 mg BIW
Part A2: M4344 100 mg BID
Experimental
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 100 mg BID
Part A2: M4344 150 mg QD
Experimental
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 150 mg QD
Part A2: M4344 250 mg QD
Experimental
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 250 mg QD
Part A2: M4344 350 mg QD
Experimental
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 350 mg QD
Part B1: M4344 350 mg + Carboplatin
Experimental
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 350 mg QD
Drug: Carboplatin
Part B1: M4344 400 mg + Carboplatin
Experimental
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 400 mg
Drug: Carboplatin
Part B1: M4344 500 mg + Carboplatin
Experimental
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 500 mg
Drug: Carboplatin
Part C: M4344 250 mg QD
Experimental
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Drug: M4344 250 mg QD
Part A: M4344 10 mg BIW
VX-803
M4344 20 mg BIW
Drug
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A: M4344 20 mg BIW
VX-803
M4344 40 mg BIW
Drug
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A: M4344 40 mg BIW
VX-803
M4344 80 mg BIW
Drug
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A: M4344 80 mg BIW
VX-803
M4344 160 mg BIW
Drug
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A: M4344 160 mg BIW
VX-803
M4344 300 mg BIW
Drug
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A: M4344 300 mg BIW
VX-803
M4344 450 mg BIW
Drug
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A: M4344 450 mg BIW
VX-803
M4344 700 mg BIW
Drug
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A: M4344 700 mg BIW
VX-803
M4344 1050 mg BIW
Drug
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A: M4344 1050 mg BIW
VX-803
M4344 1200 mg BIW
Drug
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A: M4344 1200 mg BIW
VX-803
M4344 100 mg BID
Drug
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A2: M4344 100 mg BID
VX-803
M4344 150 mg QD
Drug
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A2: M4344 150 mg QD
VX-803
M4344 250 mg QD
Drug
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A2: M4344 250 mg QD
Part C: M4344 250 mg QD
VX-803
M4344 350 mg QD
Drug
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part A2: M4344 350 mg QD
Part B1: M4344 350 mg + Carboplatin
VX-803
M4344 400 mg
Drug
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part B1: M4344 400 mg + Carboplatin
VX-803
M4344 500 mg
Drug
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part B1: M4344 500 mg + Carboplatin
VX-803
Carboplatin
Drug
Participants received intravenous infusion of Carboplatin at a dose of Area Under Curve5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Part B1: M4344 350 mg + Carboplatin
Part B1: M4344 400 mg + Carboplatin
Part B1: M4344 500 mg + Carboplatin
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator.
up to safety follow-up visit (Week 124.9)
Part A: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was decided by investigator. Number of participants with clinically significant abnormalities in 12-Lead ECGs were reported.
up to safety follow-up visit (Week 124.9)
Part A: Maximum Tolerated Dose (MTD) of M4344 Administered Twice Weekly (BIW)
MTD as per NCI-CTCAE v4.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for > 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for > 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for > 2 weeks.
up to Cycle 1 (each cycle is of 21 days)
Part A2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.
up to safety follow-up visit (Week 39)
Part A2: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0)
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
up to safety follow-up visit (Week 39)
Part A2: Number of Participants With Clinically Relevant Findings in Vital Signs
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings were reported. Clinical relevance was decided by Investigator.
up to safety follow-up visit (Week 39)
Part A2: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical Significance was determined by investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported.
up to safety follow-up visit (Week 39)
Part A2: Maximum Tolerated Dose (MTD) of M4344 Administered With a Dose Dense Schedule
MTD as per NCI-CTCAE v5.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for > 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for > 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for > 2 weeks.
up to Cycle 1 (each cycle is of 21 days)
Part B1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.
up to Safety follow-up (Week 92.3)
Part B1: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0)
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v4.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
up to Safety follow-up (Week 92.3)
Part B1: Number of Participants With Clinically Relevant Findings in Vital Signs
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator.
up to Safety follow-up (Week 92.3)
Part B1: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was determined by Investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported.
up to Safety follow-up (Week 92.3)
Part B1: Maximum Tolerated Dose (MTD) of M4344 (Monotherapy) Administered in Combination With Carboplatin
MTD as per NCI-CTCAE v4.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for > 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for > 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for > 2 weeks.
up to Cycle 1 (each cycle is of 21 days)
Part C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related AEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
AE: any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of a medicinal product, regardless if it is considered related to medicinal product. Serious AE: AE that resulted in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: AEs that were reported/worsened on/after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs. Treatment related AEs: reasonably related to the study drug/study treatment. AE could medically (pharmacologically/clinically) be attributed to the study drug/study treatment under study in this clinical study protocol.
up to Safety follow-up (Week 31.1)
Part C: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0)
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
up to Safety follow-up (Week 31.1)
Part C: Number of Participants With Clinically Relevant Findings in Vital Signs
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator.
up to Safety follow-up (Week 31.1)
Part C: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was determined by investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported.
up to Safety follow-up (Week 31.1)
Part C: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
OR is defined as the confirmed assessment of best overall response of complete response (CR) or partial response (PR). CR is defined as disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Time from first dose of study treatment up to 6.4 years
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of M4344
Tmax was obtained directly from the plasma concentration versus time curve.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Terminal Elimination Half-Life (T1/2) of M4344
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Apparent Clearance (CL/f) of M4344
CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc [Cmax]) of M4344
Accumulation ratio of Cmax was calculated as Cmax, after dosing on Day 8 divided by Cmax, after dosing on Day 1 of Cycle 1.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Accumulation Ratio for Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (Racc [AUC0-t]) of M4344
Accumulation ratio of AUC0-t was calculated as AUC0-t, after dosing on Day 8 divided by AUC0-t, after dosing on Day 1 of Cycle 1.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344
Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in nanogram per milliliter per milligram (ng/mL/mg).
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344
AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose. AUC0-t/dose was measured in nanogram*hour per milliliter per milligram (ng*h/mL/mg).
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344
AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
Part A: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
The OR was defined as the confirmed assessment of best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.
Time from first dose of study treatment up to 4.3 years
Part A: Number of Participants With Stable Disease (SD) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
SD is defined as neither sufficient increase to qualify for progression disease (PD) nor sufficient shrinkage to qualify for partial response (PR). PR: at least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. PD: at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time from first dose of study treatment up to 4.3 years
Part A2: Maximum Observed Plasma Concentration (Cmax) of M4344
Cmax was obtained directly from the plasma concentration versus time curve.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
Part A2: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (in BID arms), 24 hours post-dose (in QD arms) on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Time to Reach Maximum Plasma Concentration (Tmax) of M4344
Tmax was obtained directly from the plasma concentration versus time curve.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Terminal Elimination Half-Life (T1/2) of M4344
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Apparent Clearance (CL/f) of M4344
CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
Part A2: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc [Cmax]) of M4344
Accumulation ratio of Cmax was calculated as Cmax, after dosing on Day 8 divided by Cmax, after dosing on Day 1 of Cycle 1.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Accumulation Ratio for Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (Racc [AUC0-t]) of M4344
Accumulation ratio of AUC0-t was calculated as AUC0-t, after dosing on Day 8 divided by AUC0-t, after dosing on Day 1 of Cycle 1.
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (in BID arms), 24 hours post-dose (in QD arms) on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Accumulation Ratio for Area Under the Plasma Concentration Time Curve (Racc [AUC]) of M4344
Accumulation ratio of AUC was calculated as AUC, after dosing on Day 8 divided by AUC, after dosing on Day 1 of Cycle 1.
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344
Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in nanogram per milliliter per milligram (ng/mL/mg).
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344
AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose. AUC0-inf/Dose was measured in nanogram*hour per milliliter per milligram (ng*h/mL/mg).
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
Part A2: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344
AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose.
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (in BID arms), 24 hours post-dose (in QD arms) on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
Part A2: Number of Participants With Stable Disease (SD) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
SD is defined as neither sufficient increase to qualify for progression disease (PD) nor sufficient shrinkage to qualify for partial response (PR). PR: at least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. PD: at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time from first dose of study treatment up to 6.2 years
Part A2: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
The OR was defined as the confirmed assessment of best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.
Time from first dose of study treatment up to 6.2 years
Part B1: Maximum Observed Plasma Concentration (Cmax) of M4344
Cmax was obtained directly from the plasma concentration versus time curve.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1:Time to Reach Maximum Plasma Concentration (Tmax) of M4344
Tmax was obtained directly from the plasma concentration versus time curve.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1: Terminal Elimination Half-Life (T1/2) of M4344
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1: Apparent Clearance (CL/f) of M4344
CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344
Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344
AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344
AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose.
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
Part B1: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
The OR was defined as the confirmed assessment of best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.
Time from first dose of study treatment up to 5.2 years
Part C: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Confirmed BOR is defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the treatment start date until documented disease progression. CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30%reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions.
Time from first dose of study treatment up to 6.4 years
Part C: Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Investigator
PFS is defined as the time from start of study treatment to progression disease (PD) or death. PD: at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates.
Time from first dose of study treatment up to 6.4 years
Part C: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time from first documentation of objective response, assessed up to 6.4 years
Part C: Overall Survival (OS)
OS was defined as the time from treatment start to the date of death due to any cause. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date. OS was measured using Kaplan-Meier (KM) estimates.
Time from first dose of study treatment up to 6.4 years
Part C: Maximum Observed Plasma Concentration (Cmax) of M4344
Cmax was obtained directly from the plasma concentration versus time curve.
Pre-dose up to 2 hours post-dose on Cycle 1 Day 1; Pre-dose up to 1 hours post-dose on Cycle 1 Day 8 and Cycle 1 Day 15 (each cycle is of 21 days)
Part C: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Pre-dose up to 2 hours post-dose on Cycle 1 Day 1; Pre-dose up to 1 hours post-dose on Cycle 1 Day 8 and Cycle 1 Day 15 (each cycle is of 21 days)
Part C: Time to Reach Maximum Plasma Concentration (Tmax) of M4344
Tmax was obtained directly from the plasma concentration versus time curve.
Pre-dose up to 2 hours post-dose on Cycle 1 Day 1; Pre-dose up to 1 hours post-dose on Cycle 1 Day 8 and Cycle 1 Day 15 (each cycle is of 21 days)
START Madrid. Fundacion Jimenez Diaz- Oncologia-Fase I
Madrid
Spain
"Hospital Clinico Universitario de Valencia Servicio de Hematologia y Oncologia Medica"
Valencia
Spain
Sarah Cannon Research Institute UK
London
Greater London
W1G 6AD
United Kingdom
Royal Marsden Hospital
Sutton
Surrey
United Kingdom
Derived
Burris HA, Berlin J, Arkenau T, Cote GM, Lolkema MP, Ferrer-Playan J, Kalapur A, Bolleddula J, Locatelli G, Goddemeier T, Gounaris I, de Bono J. A phase I study of ATR inhibitor gartisertib (M4344) as a single agent and in combination with carboplatin in patients with advanced solid tumours. Br J Cancer. 2024 Apr;130(7):1131-1140. doi: 10.1038/s41416-023-02436-2. Epub 2024 Jan 29.
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG010
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG011
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG012
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG013
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG014
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG015
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG016
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG017
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
FG0002 subjects
FG0011 subjects
FG0022 subjects
FG0031 subjects
FG0041 subjects
FG0052 subjects
FG0064 subjects
FG00712 subjects
FG00810 subjects
FG0097 subjects
FG0107 subjects
FG0115 subjects
FG0127 subjects
FG0137 subjects
FG0143 subjects
FG0157 subjects
FG0166 subjects
FG01713 subjects
COMPLETED
FG0002 subjects
FG0011 subjects
FG0022 subjects
FG0031 subjects
FG0041 subjects
FG0052 subjects
FG0064 subjects
FG00712 subjects
FG00810 subjects
FG0097 subjects
FG0107 subjects
FG0115 subjects
FG0127 subjects
FG0137 subjects
FG0143 subjects
FG0157 subjects
FG0166 subjects
FG01713 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG010
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG011
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG012
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG013
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG014
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG015
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG016
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG017
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
BG018
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0002
BG0011
BG0022
BG0031
BG0041
BG0052
BG0064
BG00712
BG00810
BG0097
BG0107
BG0115
BG0127
BG0137
BG0143
BG0157
BG0166
BG01713
BG01897
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0001
BG0011
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.
The safety analysis set (SAF) included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to safety follow-up visit (Week 124.9)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG003
Title
Denominators
Categories
Title
Measurements
OG0002
OG0011
OG0022
OG003
Primary
Part A: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0)
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v4.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
The safety analysis set (SAF) included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to safety follow-up visit (Week 124.9)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part A: Number of Participants With Clinically Relevant Findings in Vital Signs
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator.
The safety analysis set (SAF) included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to safety follow-up visit (Week 124.9)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part A: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was decided by investigator. Number of participants with clinically significant abnormalities in 12-Lead ECGs were reported.
The safety analysis set (SAF) included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to safety follow-up visit (Week 124.9)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Primary
Part A: Maximum Tolerated Dose (MTD) of M4344 Administered Twice Weekly (BIW)
MTD as per NCI-CTCAE v4.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for > 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for > 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for > 2 weeks.
Dose Limiting Toxicity (DLT) Evaluable Set: included all enrolled participants who received at least 1 dose of M4344 and either: Experienced a DLT before the end of Cycle 1 or Received at least 80% of scheduled M4344 doses through the end of Cycle 1.
Posted
Number
milligrams (mg)
up to Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344
All participants who received escalated oral doses of M4344 (10 mg, 20 mg, 40 mg, 80 mg, 160 mg, 300 mg, 450 mg, 700 mg, 1050 mg and 1200 mg), twice weekly until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part A2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.
The SAF included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to safety follow-up visit (Week 39)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part A2: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0)
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
The SAF included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to safety follow-up visit (Week 39)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part A2: Number of Participants With Clinically Relevant Findings in Vital Signs
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings were reported. Clinical relevance was decided by Investigator.
The SAF included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to safety follow-up visit (Week 39)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part A2: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical Significance was determined by investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported.
The SAF included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to safety follow-up visit (Week 39)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Primary
Part A2: Maximum Tolerated Dose (MTD) of M4344 Administered With a Dose Dense Schedule
MTD as per NCI-CTCAE v5.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for > 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for > 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for > 2 weeks.
DLT evaluable set included all enrolled participants who received at least one dose of M4344 and either: Experienced a DLT before the end of Cycle 1 or Received at least 80% of scheduled M4344 doses through the end of Cycle 1.
Posted
Number
mg
up to Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344
All participants who received escalated oral doses of M4344 (100 mg; BID, 150 mg, 250 mg or 350 mg; QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part B1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.
The SAF included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to Safety follow-up (Week 92.3)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Primary
Part B1: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0)
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v4.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
The SAF included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to Safety follow-up (Week 92.3)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part B1: Number of Participants With Clinically Relevant Findings in Vital Signs
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator.
The SAF included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to Safety follow-up (Week 92.3)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Primary
Part B1: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was determined by Investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported.
The SAF included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg.
Posted
Count of Participants
Participants
up to Safety follow-up (Week 92.3)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part B1: Maximum Tolerated Dose (MTD) of M4344 (Monotherapy) Administered in Combination With Carboplatin
MTD as per NCI-CTCAE v4.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for > 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for > 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for > 2 weeks.
DLT evaluable set included all enrolled participants who received at least one dose of M4344 and either: Experienced a DLT before the end of Cycle 1 or Received Carboplatin dose on Day 1 and M4344 dose on Days 2 and 9.
Posted
Number
mg
up to Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344
All participants who received escalated oral doses of M4344 (350 mg or 400 mg or 500 mg) on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related AEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
AE: any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of a medicinal product, regardless if it is considered related to medicinal product. Serious AE: AE that resulted in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: AEs that were reported/worsened on/after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs. Treatment related AEs: reasonably related to the study drug/study treatment. AE could medically (pharmacologically/clinically) be attributed to the study drug/study treatment under study in this clinical study protocol.
The SAF included all participants who received at least one dose of study drug.
Posted
Count of Participants
Participants
up to Safety follow-up (Week 31.1)
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part C: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0)
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
The SAF included all participants who received at least one dose of study drug.
Posted
Count of Participants
Participants
up to Safety follow-up (Week 31.1)
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Primary
Part C: Number of Participants With Clinically Relevant Findings in Vital Signs
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator.
The SAF included all participants who received at least one dose of study drug.
Posted
Count of Participants
Participants
up to Safety follow-up (Week 31.1)
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG000
Primary
Part C: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was determined by investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported.
The SAF included all participants who received at least one dose of study drug.
Posted
Count of Participants
Participants
up to Safety follow-up (Week 31.1)
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG000
Primary
Part C: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
OR is defined as the confirmed assessment of best overall response of complete response (CR) or partial response (PR). CR is defined as disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Full Analysis Set (FAS) included all participants who received at least one dose of study drug.
Posted
Number
95% Confidence Interval
percentage of participants
Time from first dose of study treatment up to 6.4 years
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG000
Secondary
Part A: Maximum Observed Plasma Concentration (Cmax) of M4344
Cmax was obtained directly from the plasma concentration versus time curve.
The Pharmacokinetic Analysis Set (PAS) included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter (ng/mL)
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Secondary
Part A: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hour per milliliter (ng*h/mL)
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
The Pharmacokinetic Analysis Set (PAS) included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Secondary
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of M4344
Tmax was obtained directly from the plasma concentration versus time curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Median
Full Range
hours
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A: Terminal Elimination Half-Life (T1/2) of M4344
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A: Apparent Clearance (CL/f) of M4344
CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
liter per hour
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
liters
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Secondary
Part A: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc [Cmax]) of M4344
Accumulation ratio of Cmax was calculated as Cmax, after dosing on Day 8 divided by Cmax, after dosing on Day 1 of Cycle 1.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ratio
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Secondary
Part A: Accumulation Ratio for Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (Racc [AUC0-t]) of M4344
Accumulation ratio of AUC0-t was calculated as AUC0-t, after dosing on Day 8 divided by AUC0-t, after dosing on Day 1 of Cycle 1.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ratio
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Secondary
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344
Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in nanogram per milliliter per milligram (ng/mL/mg).
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL/mg
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Secondary
Part A: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344
AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose. AUC0-t/dose was measured in nanogram*hour per milliliter per milligram (ng*h/mL/mg).
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL/mg
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344
AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL/mg
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Secondary
Part A: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
The OR was defined as the confirmed assessment of best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.
Full analysis set (FAS): all enrolled participants who satisfy all of the following criteria: received at least 1 dose of study drug with the actual amount > 0 mg; have a baseline scan with a measurable target lesion (sum of diameters of all target lesions > 0 mm) and have at least 1 disease assessment on treatment with a measurable target lesion (sum of diameters of all target lesions >= 0 mm); or subjects who have discontinued the study due to either progressive disease or death.
Posted
Number
95% Confidence Interval
percentage of participants
Time from first dose of study treatment up to 4.3 years
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A: Number of Participants With Stable Disease (SD) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
SD is defined as neither sufficient increase to qualify for progression disease (PD) nor sufficient shrinkage to qualify for partial response (PR). PR: at least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. PD: at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
FAS: all enrolled participants who satisfy all of the following criteria: received at least 1 dose of study drug with the actual amount > 0 mg; have a baseline scan with a measurable target lesion (sum of diameters of all target lesions > 0 mm) and have at least 1 disease assessment on treatment with a measurable target lesion (sum of diameters of all target lesions >= 0 mm); or subjects who have discontinued the study due to either progressive disease or death.
Posted
Count of Participants
Participants
Time from first dose of study treatment up to 4.3 years
ID
Title
Description
OG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A2: Maximum Observed Plasma Concentration (Cmax) of M4344
Cmax was obtained directly from the plasma concentration versus time curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Secondary
Part A2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A2: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (in BID arms), 24 hours post-dose (in QD arms) on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A2: Time to Reach Maximum Plasma Concentration (Tmax) of M4344
Tmax was obtained directly from the plasma concentration versus time curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Median
Full Range
hours
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Secondary
Part A2: Terminal Elimination Half-Life (T1/2) of M4344
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A2: Apparent Clearance (CL/f) of M4344
CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
liter per hour
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A2: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
liters
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A2: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc [Cmax]) of M4344
Accumulation ratio of Cmax was calculated as Cmax, after dosing on Day 8 divided by Cmax, after dosing on Day 1 of Cycle 1.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ratio
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Secondary
Part A2: Accumulation Ratio for Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (Racc [AUC0-t]) of M4344
Accumulation ratio of AUC0-t was calculated as AUC0-t, after dosing on Day 8 divided by AUC0-t, after dosing on Day 1 of Cycle 1.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ratio
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (in BID arms), 24 hours post-dose (in QD arms) on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Secondary
Part A2: Accumulation Ratio for Area Under the Plasma Concentration Time Curve (Racc [AUC]) of M4344
Accumulation ratio of AUC was calculated as AUC, after dosing on Day 8 divided by AUC, after dosing on Day 1 of Cycle 1.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ratio
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Secondary
Part A2: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344
Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in nanogram per milliliter per milligram (ng/mL/mg).
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL/mg
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A2: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344
AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose. AUC0-inf/Dose was measured in nanogram*hour per milliliter per milligram (ng*h/mL/mg).
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL/mg
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Secondary
Part A2: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344
AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL/mg
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (in BID arms), 24 hours post-dose (in QD arms) on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part A2: Number of Participants With Stable Disease (SD) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
SD is defined as neither sufficient increase to qualify for progression disease (PD) nor sufficient shrinkage to qualify for partial response (PR). PR: at least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. PD: at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
FAS is defined as all enrolled participants who received at least 1 dose of study drug, have a baseline scan, and received at least one disease assessment while on treatment.
Posted
Count of Participants
Participants
Time from first dose of study treatment up to 6.2 years
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Secondary
Part A2: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
The OR was defined as the confirmed assessment of best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.
FAS is defined as all enrolled participants who received at least 1 dose of study drug, have a baseline scan, and received at least one disease assessment while on treatment.
Posted
Number
90% Confidence Interval
percentage of participants
Time from first dose of study treatment up to 6.2 years
ID
Title
Description
OG000
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Secondary
Part B1: Maximum Observed Plasma Concentration (Cmax) of M4344
Cmax was obtained directly from the plasma concentration versus time curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Secondary
Part B1: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part B1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Secondary
Part B1:Time to Reach Maximum Plasma Concentration (Tmax) of M4344
Tmax was obtained directly from the plasma concentration versus time curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received.
Posted
Median
Full Range
hours
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part B1: M4344 500 mg + Carboplatin
Secondary
Part B1: Terminal Elimination Half-Life (T1/2) of M4344
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part B1: Apparent Clearance (CL/f) of M4344
CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
liter per hour
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part B1: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
liters
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Secondary
Part B1: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344
Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL/mg
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part B1: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344
AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL/mg
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part B1: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344
AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose.
The PAS included all enrolled participants who received at least one dose of M4344 with the actual amount > 0 mg and provide at least one measurable post-dose concentration. Participants were analyzed according to the actual treatment they received. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL/mg
Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part B1: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
The OR was defined as the confirmed assessment of best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.
FAS is defined as all enrolled participants who received at least 1 dose of study treatment, have a baseline scan with a measurable target lesion, and at least one on-treatment disease assessment or have discontinued the study due to either progressive disease or death.
Posted
Number
90% Confidence Interval
percentage of participants
Time from first dose of study treatment up to 5.2 years
ID
Title
Description
OG000
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Secondary
Part C: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Confirmed BOR is defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the treatment start date until documented disease progression. CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30%reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions.
FAS included all participants who received at least one dose of study drug.
Posted
Count of Participants
Participants
Time from first dose of study treatment up to 6.4 years
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
Secondary
Part C: Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Investigator
PFS is defined as the time from start of study treatment to progression disease (PD) or death. PD: at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates.
FAS included all participants who received at least one dose of study drug.
Posted
Median
95% Confidence Interval
months
Time from first dose of study treatment up to 6.4 years
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG000
Secondary
Part C: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
As per planned analysis, DoR was not analyzed due to the small number of participants and the low likelihood that any participant would experience an objective response.
Posted
Time from first documentation of objective response, assessed up to 6.4 years
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
Secondary
Part C: Overall Survival (OS)
OS was defined as the time from treatment start to the date of death due to any cause. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date. OS was measured using Kaplan-Meier (KM) estimates.
FAS included all participants who received at least one dose of study drug. The summarized data was not available for these arms therefore individual data was presented. Here, "Overall Number of Participants" signifies those participants who were evaluable for this outcome measure and "number analyzed" = specific participants evaluated in the arm.
Posted
Number
months
Time from first dose of study treatment up to 6.4 years
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG000
Secondary
Part C: Maximum Observed Plasma Concentration (Cmax) of M4344
Cmax was obtained directly from the plasma concentration versus time curve.
As per changes in planned analysis, the outcome measures related to pharmacokinetic parameters were not assessed for Part C.
Posted
Pre-dose up to 2 hours post-dose on Cycle 1 Day 1; Pre-dose up to 1 hours post-dose on Cycle 1 Day 8 and Cycle 1 Day 15 (each cycle is of 21 days)
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG000
Secondary
Part C: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
As per changes in planned analysis, the outcome measures related to pharmacokinetic parameters were not assessed for Part C.
Posted
Pre-dose up to 2 hours post-dose on Cycle 1 Day 1; Pre-dose up to 1 hours post-dose on Cycle 1 Day 8 and Cycle 1 Day 15 (each cycle is of 21 days)
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG000
Secondary
Part C: Time to Reach Maximum Plasma Concentration (Tmax) of M4344
Tmax was obtained directly from the plasma concentration versus time curve.
As per changes in planned analysis, the outcome measures related to pharmacokinetic parameters were not assessed for Part C.
Posted
Pre-dose up to 2 hours post-dose on Cycle 1 Day 1; Pre-dose up to 1 hours post-dose on Cycle 1 Day 8 and Cycle 1 Day 15 (each cycle is of 21 days)
ID
Title
Description
OG000
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG000
Time Frame
Part A: up to Safety follow-up (Week 124.9), Part A2: up to Safety follow-up ( Week 39), Part B1: up to Safety follow-up (Week 92.3) and Part C: up to Safety follow-up (Week 31.1)
Description
Part A, A2 and B1: The SAF included all enrolled participants who received at least 1 dose of study drug (either M4344 or carboplatin (Part B1 only) with the actual amount > 0 mg. Part C: The SAF included all participants who received at least one dose of study drug. For Part A and B: MedDRA version 23.0 and for Part A2 and C: MedDRA version 24.0.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part A: M4344 10 mg BIW
Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
0
2
1
2
2
2
EG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
0
1
0
1
1
1
EG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
1
2
1
2
1
2
EG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
0
1
0
1
1
1
EG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
1
1
1
1
1
1
EG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
1
2
0
2
2
2
EG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
1
4
2
4
4
4
EG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
8
12
6
12
12
12
EG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
3
10
6
10
10
10
EG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
1
7
4
7
7
7
EG010
Part A2: M4344 100 mg BID
Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
5
7
5
7
7
7
EG011
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
3
5
1
5
5
5
EG012
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
2
7
2
7
7
7
EG013
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
3
7
5
7
7
7
EG014
Part B1: M4344 350 mg + Carboplatin
Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
1
3
1
3
3
3
EG015
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
4
7
4
7
7
7
EG016
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
2
6
3
6
6
6
EG017
Part C: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
6
13
7
13
13
13
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal pain
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG0030 affected1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0081 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0171 affected13 at risk
Nausea
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Disease progression
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pyrexia
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Urosepsis
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Colorectal cancer metastatic
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Cauda equina syndrome
Nervous system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0021 affected2 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pneumonia aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Fatigue
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Malaise
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Biliary sepsis
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Sepsis
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Transaminases increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Seizure
Nervous system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Gastrointestinal inflammation
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Death
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Euthanasia
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Anaphylactic reaction
Immune system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Syncope
Nervous system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Intestinal obstruction
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Biliary obstruction
Hepatobiliary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Streptococcal infection
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG0030 affected1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0061 affected4 at risk
EG0071 affected12 at risk
EG0081 affected10 at risk
EG0091 affected7 at risk
EG0101 affected7 at risk
EG0112 affected5 at risk
EG0124 affected7 at risk
EG0132 affected7 at risk
EG0141 affected3 at risk
EG0154 affected7 at risk
EG0163 affected6 at risk
EG0177 affected13 at risk
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Ocular hyperaemia
Eye disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0011 affected1 at risk
EG0021 affected2 at risk
EG003
Post-tussive vomiting
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0011 affected1 at risk
EG0021 affected2 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Dry eye
Eye disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Vision blurred
Eye disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Conjunctival haemorrhage
Eye disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Retinal haemorrhage
Eye disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Duodenal obstruction
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Eructation
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Asthenia
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Chills
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Fatigue
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Influenza like illness
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Infusion site swelling
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Oedema peripheral
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pain
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pyrexia
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Chest pain
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Malaise
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Oedema
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Peripheral swelling
General disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hepatic function abnormal
Hepatobiliary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Jaundice
Hepatobiliary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Ocular icterus
Hepatobiliary disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Epididymitis
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Furuncle
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Incisional hernia
Injury, poisoning and procedural complications
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Radiation skin injury
Injury, poisoning and procedural complications
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0021 affected2 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0021 affected2 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Weight decreased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Weight increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Hepatic enzyme increase
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Transaminases increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Blood urea increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Mean cell volume increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Platelet count decreased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
White blood cell count decreased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
White blood cell count increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Haemoglobin decreased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Neutrophil count increased
Investigations
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0021 affected2 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0021 affected2 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Groin pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0011 affected1 at risk
EG0020 affected2 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0001 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Pain in jaw
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Limb discomfort
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Tumour obstruction
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.0 and 24.0
Non-systematic Assessment
EG0000 affected2 at risk
EG0010 affected1 at risk
EG0020 affected2 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
1
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
1
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
Title
Denominators
Categories
Hematology
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
OG0090
Total Bilirubin
Title
Measurements
OG0000
OG0010
OG0020
OG003
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
OG0090
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0071
OG0080
OG0091
Units
Counts
Participants
OG00042
Title
Denominators
Categories
Title
Measurements
OG000NAMTD not determined as development focus of the study shifted to daily monotherapy dosing (Part A2).
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0007
OG0015
OG0027
OG0037
Title
Denominators
Categories
Title
Measurements
OG0007
OG0015
OG0027
OG0037
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0007
OG0015
OG0027
OG0037
Title
Denominators
Categories
Low lymphocytes
Title
Measurements
OG0001
OG0011
OG0022
OG0033
Total Bilirubin
Title
Measurements
OG0003
OG0012
OG0023
OG003
Aspartate Aminotransferase
Title
Measurements
OG0002
OG0011
OG0020
OG003
Alanine Aminotransferase
Title
Measurements
OG0002
OG0012
OG0020
OG003
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0007
OG0015
OG0027
OG0037
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0007
OG0015
OG0027
OG0037
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
Units
Counts
Participants
OG00026
Title
Denominators
Categories
Title
Measurements
OG000250
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Title
Measurements
OG0003
OG0017
OG0026
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Neutrophils
Title
Measurements
OG0001
OG0011
OG0025
Platelets
Title
Measurements
OG0001
OG0013
OG0023
Low hemoglobin
Title
Measurements
OG0001
OG0014
OG0021
Low Leukocytes
Title
Measurements
OG0000
OG0011
OG0024
Low lymphocytes
Title
Measurements
OG0001
OG0013
OG0021
Chemistry
Title
Measurements
OG0000
OG0010
OG0020
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
Units
Counts
Participants
OG00016
Title
Denominators
Categories
Title
Measurements
OG000NAMTD not determined as development focus of the study shifted to daily monotherapy dosing (Part A2).
Units
Counts
Participants
OG00013
Title
Denominators
Categories
Participants with TEAEs
Title
Measurements
OG00013
Participants with Treatment related AEs
Title
Measurements
OG00013
Units
Counts
Participants
OG00013
Title
Denominators
Categories
Low lymphocytes
Title
Measurements
OG0008
Low hemoglobin
Title
Measurements
OG0006
Total Bilirubin
Title
Measurements
OG0007
Aspartate Aminotransferase
Title
Measurements
OG0004
Alanine Aminotransferase
Title
Measurements
OG0003
13
Title
Denominators
Categories
Title
Measurements
OG0000
13
Title
Denominators
Categories
Title
Measurements
OG0006
13
Title
Denominators
Categories
Title
Measurements
OG0000.0(0.0 to 20.6)
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
ParticipantsOG0041
ParticipantsOG0052
ParticipantsOG0064
ParticipantsOG00712
ParticipantsOG00810
ParticipantsOG0097
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003
Cycle 1 Day 8
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0021
ParticipantsOG0031
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
ParticipantsOG0041
ParticipantsOG0052
ParticipantsOG0064
ParticipantsOG00712
ParticipantsOG00810
ParticipantsOG0097
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003
Cycle 1 Day 8
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0021
ParticipantsOG0031
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00710
OG0086
OG0093
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG006971± 53.6
OG0071710± 92.5
OG0081760± 122.3
OG0091540± 128.9
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
ParticipantsOG0041
ParticipantsOG0052
ParticipantsOG0064
ParticipantsOG00712
ParticipantsOG00810
ParticipantsOG0097
Title
Measurements
OG000NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003
Cycle 1 Day 8
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0021
ParticipantsOG0031
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00710
OG0086
OG0093
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
ParticipantsOG0041
ParticipantsOG0052
ParticipantsOG0064
ParticipantsOG00710
ParticipantsOG0086
ParticipantsOG0093
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003
Cycle 1 Day 8
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0021
ParticipantsOG0031
OG001
Part A: M4344 20 mg BIW
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00710
OG0086
OG0093
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
ParticipantsOG0041
ParticipantsOG0052
ParticipantsOG0064
ParticipantsOG00710
ParticipantsOG0086
ParticipantsOG0093
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003
Cycle 1 Day 8
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0021
ParticipantsOG0031
Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00710
OG0086
OG0093
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
ParticipantsOG0041
ParticipantsOG0052
ParticipantsOG0064
ParticipantsOG00710
ParticipantsOG0086
ParticipantsOG0093
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003
Cycle 1 Day 8
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0021
ParticipantsOG0031
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0021
OG0031
OG0041
OG0052
OG0063
OG0077
OG0086
OG0093
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0060.988± 37.9
OG0071.19± 67.5
OG0081.01± 163.2
OG0091.55± 17.4
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0021
OG0031
OG0041
OG0052
OG0063
OG0077
OG0086
OG0093
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0060.955± 23.7
OG0071.46± 77.8
OG0081.36± 163.7
OG0091.89± 33.6
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
ParticipantsOG0041
ParticipantsOG0052
ParticipantsOG0064
ParticipantsOG00712
ParticipantsOG00810
ParticipantsOG0097
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003
Cycle 1 Day 8
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00712
OG00810
OG0097
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
ParticipantsOG0041
ParticipantsOG0052
ParticipantsOG0064
ParticipantsOG00712
ParticipantsOG00810
ParticipantsOG0097
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003
Cycle 1 Day 8
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0031
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0011
OG0022
OG0031
OG0041
OG0052
OG0064
OG00710
OG0086
OG0093
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0062.16± 53.6
OG0072.45± 92.5
OG0081.68± 122.3
OG0091.28± 128.9
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0001
OG0011
OG0021
OG0031
OG0041
OG0051
OG0063
OG0076
OG0087
OG0094
Title
Denominators
Categories
Title
Measurements
OG0000.0(0.0 to 95.0)
OG0010.0(0.0 to 95.0)
OG0020.0(0.0 to 95.0)
OG0030.0(0.0 to 95.0)
OG0040.0(0.0 to 95.0)
OG0050.0(0.0 to 95.0)
OG0060.0(0.0 to 63.2)
OG0070.0(0.0 to 39.3)
OG0080.0(0.0 to 34.8)
OG0090.0(0.0 to 52.7)
OG002
Part A: M4344 40 mg BIW
Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A: M4344 80 mg BIW
Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG004
Part A: M4344 160 mg BIW
Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG005
Part A: M4344 300 mg BIW
Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG006
Part A: M4344 450 mg BIW
Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG007
Part A: M4344 700 mg BIW
Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG008
Part A: M4344 1050 mg BIW
Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG009
Part A: M4344 1200 mg BIW
Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0001
OG0011
OG0021
OG0031
OG0041
OG0051
OG0063
OG0076
OG0087
OG0094
Title
Denominators
Categories
Title
Measurements
OG0000
OG0011
OG0020
OG0030
OG0040
OG0050
OG0062
OG0072
OG0081
OG0091
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0027
OG0037
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG0015
ParticipantsOG0027
ParticipantsOG0037
Title
Measurements
OG000111± 40.3
OG001124± 392.2
OG002517± 78.3
OG003
Cycle 1 Day 8
ParticipantsOG0003
ParticipantsOG0014
ParticipantsOG0027
ParticipantsOG0032
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0026
OG0037
Title
Denominators
Categories
Title
Measurements
OG000217± 44.2
OG001436± 127.4
OG0021210± 95.0
OG003680± 144.1
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0027
OG0037
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG0015
ParticipantsOG0027
ParticipantsOG0037
Title
Measurements
OG000216± 43.2
OG001414± 142.9
OG0021230± 86.1
OG003
Cycle 1 Day 8
ParticipantsOG0003
ParticipantsOG0014
ParticipantsOG0027
ParticipantsOG0032
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0027
OG0037
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG0015
ParticipantsOG0027
ParticipantsOG0037
Title
Measurements
OG0001.45(0.517 to 2.00)
OG0011.62(0.467 to 2.07)
OG0021.50(0.500 to 2.00)
OG003
Cycle 1 Day 8
ParticipantsOG0003
ParticipantsOG0014
ParticipantsOG0027
ParticipantsOG0032
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0027
OG0037
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG0015
ParticipantsOG0026
ParticipantsOG0037
Title
Measurements
OG0001.32± 27.1
OG0012.47± 165.9
OG0021.74± 58.8
OG003
Cycle 1 Day 8
ParticipantsOG0003
ParticipantsOG0014
ParticipantsOG0027
ParticipantsOG0032
OG001
Part A2: M4344 150 mg QD
Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0027
OG0037
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG0015
ParticipantsOG0026
ParticipantsOG0037
Title
Measurements
OG000461± 44.2
OG001344± 127.4
OG002207± 95.0
OG003
Cycle 1 Day 8
ParticipantsOG0003
ParticipantsOG0014
ParticipantsOG0027
ParticipantsOG0032
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0026
OG0037
Title
Denominators
Categories
Title
Measurements
OG000876± 36.3
OG0011220± 661.7
OG002519± 191.1
OG0031760± 214.7
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0014
OG0027
OG0032
Title
Denominators
Categories
Title
Measurements
OG0001.08± 47.5
OG0012.26± 245.2
OG0020.733± 92.1
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0014
OG0027
OG0032
Title
Denominators
Categories
Title
Measurements
OG0001.00± 55.3
OG0011.42± 142.4
OG0020.672± 90.7
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0014
OG0027
OG0032
Title
Denominators
Categories
Title
Measurements
OG0000.997± 55.7
OG0011.32± 133.5
OG0020.676± 88.4
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0027
OG0037
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG0015
ParticipantsOG0027
ParticipantsOG0037
Title
Measurements
OG0001.11± 40.3
OG0010.829± 392.2
OG0022.07± 78.3
OG003
Cycle 1 Day 8
ParticipantsOG0003
ParticipantsOG0014
ParticipantsOG0027
ParticipantsOG0032
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0026
OG0037
Title
Denominators
Categories
Title
Measurements
OG0002.17± 44.2
OG0012.91± 127.4
OG0024.84± 95.0
OG0031.94± 144.1
OG002
Part A2: M4344 250 mg QD
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0006
OG0015
OG0027
OG0037
Title
Denominators
Categories
Cycle 1 Day 1
ParticipantsOG0006
ParticipantsOG0015
ParticipantsOG0027
ParticipantsOG0037
Title
Measurements
OG0002.16± 43.2
OG0012.76± 142.9
OG0024.93± 86.1
OG003
Cycle 1 Day 8
ParticipantsOG0003
ParticipantsOG0014
ParticipantsOG0027
ParticipantsOG0032
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0007
OG0014
OG0027
OG0035
Title
Denominators
Categories
Title
Measurements
OG0001
OG0011
OG0024
OG0032
Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG003
Part A2: M4344 350 mg QD
Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0007
OG0014
OG0027
OG0035
Title
Denominators
Categories
Title
Measurements
OG0000.0(0.0 to 34.8)
OG0010.0(0.0 to 52.7)
OG0020.0(0.0 to 34.8)
OG0030.0(0.0 to 45.1)
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Title
Measurements
OG000309± 78.1
OG001114± 191.6
OG002367± 89.8
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Title
Measurements
OG000392± 101.8
OG001268± 179.6
OG0021450± 115.6
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0014
OG0023
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001368± 147.3
OG0022570± 124.3
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Title
Measurements
OG0001.52(0.900 to 2.00)
OG0011.50(0.500 to 8.02)
OG0021.96(1.00 to 3.00)
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0014
OG0023
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0011.03± 23.6
OG0023.77± 59.1
OG001
Part B1: M4344 400 mg + Carboplatin
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0014
OG0023
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0011090± 147.3
OG002194± 124.3
Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0014
OG0023
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0011620± 155.5
OG0021060± 45.1
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Title
Measurements
OG0000.884± 78.1
OG0010.286± 191.6
OG0020.735± 89.8
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Title
Measurements
OG0001.12± 101.8
OG0010.669± 179.6
OG0022.90± 115.6
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0002
OG0014
OG0023
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0010.920± 147.3
OG0025.15± 124.3
OG002
Part B1: M4344 500 mg + Carboplatin
Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal.
Units
Counts
Participants
OG0003
OG0017
OG0026
Title
Denominators
Categories
Title
Measurements
OG0000.0(0.0 to 63.2)
OG00114.3(0.7 to 52.1)
OG0020.0(0.0 to 39.3)
OG00013
Title
Denominators
Categories
Complete response (CR)
Title
Measurements
OG0000
Partial response (PR)
Title
Measurements
OG0000
Stable disease (SD)
Title
Measurements
OG0003
Progressive disease (PD)
Title
Measurements
OG0008
Non-CR/Non-PD
Title
Measurements
OG0000
Non-evaluable
Title
Measurements
OG0002
13
Title
Denominators
Categories
Title
Measurements
OG0001.6(0.8 to 2.1)
OG000
0
6
Title
Denominators
Categories
Participant 1
ParticipantsOG0001
Title
Measurements
OG0001.91
Participant 2
ParticipantsOG0001
Title
Measurements
OG0000.79
Participant 3
ParticipantsOG0001
Title
Measurements
OG0001.61
Participant 4
ParticipantsOG0001
Title
Measurements
OG0003.98
Participant 5
ParticipantsOG0001
Title
Measurements
OG0002.53
Participant 6
ParticipantsOG0001
Title
Measurements
OG0002.63
0
0
0
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0101 affected7 at risk
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EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0171 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0151 affected7 at risk
EG0160 affected6 at risk
EG0171 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0151 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0171 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0061 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0081 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0061 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0081 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0071 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0121 affected7 at risk
EG0131 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0101 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0121 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0151 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0111 affected5 at risk
EG0121 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0152 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0131 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0151 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0151 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0151 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0071 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0101 affected7 at risk
EG0110 affected5 at risk
EG0121 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0061 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0121 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0151 affected7 at risk
EG0160 affected6 at risk
EG0170 affected13 at risk
0 affected
1 at risk
EG0040 affected1 at risk
EG0050 affected2 at risk
EG0060 affected4 at risk
EG0070 affected12 at risk
EG0080 affected10 at risk
EG0090 affected7 at risk
EG0100 affected7 at risk
EG0110 affected5 at risk
EG0120 affected7 at risk
EG0130 affected7 at risk
EG0140 affected3 at risk
EG0150 affected7 at risk
EG0161 affected6 at risk
EG0170 affected13 at risk
0
OG0040
OG0050
OG0060
OG0075
OG0086
OG0094
3
4
3
NA
± NA
Geometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG006376± 64.2
OG007516± 83.6
OG008395± 73.2
OG009576± 79.9
Participants
OG004
1
ParticipantsOG0052
ParticipantsOG0063
ParticipantsOG0077
ParticipantsOG0086
ParticipantsOG0093
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG006342± 136.6
OG007675± 65.7
OG008328± 313.1
OG009486± 23.8
NA
± NA
Geometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG006948± 56.4
OG0071830± 102.0
OG0081390± 64.5
OG0092220± 105.9
Participants
OG004
1
ParticipantsOG0052
ParticipantsOG0063
ParticipantsOG0077
ParticipantsOG0086
ParticipantsOG0093
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG006809± 96.6
OG0072670± 91.2
OG0081550± 295.1
OG0091880± 74.0
NA
(NA to NA)
Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0061.51(0.663 to 2.15)
OG0072.00(0.533 to 8.00)
OG0082.06(1.50 to 4.00)
OG0093.07(1.50 to 4.07)
Participants
OG004
1
ParticipantsOG0052
ParticipantsOG0063
ParticipantsOG0077
ParticipantsOG0086
ParticipantsOG0093
Title
Measurements
OG000NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0061.22(1.05 to 1.50)
OG0072.00(1.57 to 3.95)
OG0084.00(1.52 to 8.05)
OG0093.95(3.00 to 4.00)
NA
± NA
Geometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0062.22± 99.0
OG0073.33± 42.3
OG0084.61± 65.2
OG0093.60± 39.9
Participants
OG004
1
ParticipantsOG0052
ParticipantsOG0063
ParticipantsOG0076
ParticipantsOG0082
ParticipantsOG0090
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0062.19± 220.1
OG0073.11± 64.2
OG008NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
NA
± NA
Geometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG006464± 53.6
OG007409± 92.5
OG008597± 122.3
OG009781± 128.9
Participants
OG004
1
ParticipantsOG0052
ParticipantsOG0063
ParticipantsOG0076
ParticipantsOG0082
ParticipantsOG0090
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG006513± 78.2
OG007221± 114.3
OG008NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
NA
± NA
Geometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0061480± 187.9
OG0071960± 116.0
OG0083970± 95.8
OG0094060± 211.6
Participants
OG004
1
ParticipantsOG0052
ParticipantsOG0063
ParticipantsOG0076
ParticipantsOG0082
ParticipantsOG0090
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0061620± 716.8
OG007993± 59.6
OG008NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
NA
± NA
Geometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0060.835± 64.2
OG0070.738± 83.6
OG0080.376± 73.2
OG0090.480± 79.9
Participants
OG004
1
ParticipantsOG0052
ParticipantsOG0063
ParticipantsOG0077
ParticipantsOG0086
ParticipantsOG0093
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0060.760± 136.6
OG0070.964± 65.7
OG0080.312± 313.1
OG0090.405± 23.8
NA
± NA
Geometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0062.11± 56.4
OG0072.61± 102.0
OG0081.32± 64.5
OG0091.85± 105.9
Participants
OG004
1
ParticipantsOG0052
ParticipantsOG0063
ParticipantsOG0077
ParticipantsOG0086
ParticipantsOG0093
Title
Measurements
OG000NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG002NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG004NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG005NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
OG0061.80± 96.6
OG0073.82± 91.2
OG0081.47± 295.1
OG0091.57± 74.0
265
± 152.7
Title
Measurements
OG000114± 32.3
OG001244± 59.3
OG002379± 88.9
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
703
± 142.7
Title
Measurements
OG000236± 55.4
OG001627± 58.9
OG002829± 101.4
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
1.10
(0.683 to 3.02)
Title
Measurements
OG0001.03(1.00 to 1.43)
OG0011.28(0.500 to 2.00)
OG0021.50(0.500 to 1.95)
OG003NA(NA to NA)Median and Full range were not to be calculated if fewer than 3 participants have reportable parameter values.
2.37
± 60.9
Title
Measurements
OG0001.36± 58.7
OG0011.31± 28.9
OG0021.31± 18.7
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
515
± 144.1
Title
Measurements
OG000424± 55.4
OG001239± 58.9
OG002302± 101.4
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
0.758
± 152.7
Title
Measurements
OG0001.14± 32.3
OG0011.63± 59.3
OG0021.52± 88.9
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.
2.01
± 142.7
Title
Measurements
OG0002.36± 55.4
OG0014.18± 58.9
OG0023.32± 101.4
OG003NA± NAGeometric Mean and Geometric Coefficient of Variation were not to be calculated if fewer than 3 participants have reportable parameter values.