Effects of Fluconazole and Itraconazole CYP3A-Mediated In... | NCT02122770 | Trialant
NCT02122770
Sponsor
Millennium Pharmaceuticals, Inc.
Status
Completed
Last Update Posted
Jan 7, 2019Actual
Enrollment
51Actual
Phase
Phase 1
Conditions
Advanced Solid Tumors
Interventions
MLN4924
Fluconazole
Itraconazole
Docetaxel
Carboplatin
Paclitaxel
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT02122770
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
C15011
Secondary IDs
ID
Type
Description
Link
U1111-1155-6191
Other Identifier
World Health Organization
Brief Title
Effects of Fluconazole and Itraconazole CYP3A-Mediated Inhibition on the Pharmacokinetics, Safety, and Tolerability of MLN4924 in Participants With Advanced Solid Tumors
Official Title
A Phase 1 Study to Evaluate the Effects of Fluconazole and Itraconazole CYP3A-Mediated Inhibition on the Pharmacokinetics, Safety, and Tolerability of MLN4924 in Patients With Advanced Solid Tumors
Acronym
Not provided
Organization
TakedaINDUSTRY
Status Module
Record Verification Date
Jun 2018
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
Apr 1, 2014Actual
Primary Completion Date
Jun 5, 2017Actual
Completion Date
Jun 5, 2017Actual
First Submitted Date
Apr 23, 2014
First Submission Date that Met QC Criteria
Apr 23, 2014
First Posted Date
Apr 25, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 7, 2018
Results First Submitted that Met QC Criteria
Jun 20, 2018
Results First Posted Date
Jan 7, 2019Actual
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
Jun 20, 2018
Last Update Posted Date
Jan 7, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Millennium Pharmaceuticals, Inc.INDUSTRY
Collaborators
Not provided
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 primary purpose of this study is to assess the effect of multiple-dose administration of fluconazole on the single-dose intravenous (IV) pharmacokinetics (PK) of MLN4924; and to assess the effect of multiple-dose administration of itraconazole on the single-dose IV PK of MLN4924.
Detailed Description
The drug being tested in this study is MLN4924. MLN4924 is being evaluated to assess drug-drug interactions (DDIs) with the moderate and strong CYP3A inhibitors, fluconazole and itraconazole, respectively, in participants with advanced solid tumors. This study will look at the blood concentrations of MLN4924 as it relates to treatment with fluconazole and itraconazole.
The study will enroll approximately 52 participants. In Part A, participants will be administered MLN4924 via a 1-hour (+- 5 minutes) intravenous (IV) infusion in combination with either fluconazole or itraconazole administered orally. After participants complete Part A, they will have the opportunity to begin treatment in Part B. In Part B, participants will be administered MLN4924 via a 1-hour (+- 5 minutes) IV infusion in combination with either docetaxel or carboplatin + paclitaxel, the three of which would also be administered intravenously.
This multi-center trial will be conducted in the United States. Participation in Part A of this study will include a screening visit and two weeks of treatment; participation in Part B of this study will include up to an 8-week drug washout period (from last dosing in Part A) and treatment until participants experience symptomatic deterioration, progressive disease, until treatment is discontinued for another reason, or until the study is stopped.
Conditions Module
Conditions
Advanced Solid Tumors
Keywords
Drug Therapy
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
51Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
MLN4924 + Fluconazole
Experimental
Part A: MLN4924, 8 milligram per square meter (mg/m^2), intravenously, once on Days 1 and 8; and fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
Part B: MLN4924, at a dose previously deemed tolerable, given on Days 1, 3, and 5 of each 21-day Cycle (Study C15010, Clinicaltrials.gov Identifier # NCT01862328) in combination with docetaxel or carboplatin + paclitaxel at standard dose regimen on Day 1 of each 21-day Cycle.
Drug: MLN4924
Drug: Fluconazole
Drug: Docetaxel
Drug: Carboplatin
Drug: Paclitaxel
MLN4924 + Itraconazole
Experimental
Part A: MLN4924, 8-mg/m^2, intravenously, once on Days 1 and 8; and itraconazole, 200 mg, oral solution, once daily on Days 4-10.
Part A (safety lead-in step): MLN4924, 15mg/m^2, intravenously, once on Days 1 and 8; and itraconazole, 200 mg, oral solution, once daily on Days 4-10.
Part A: MLN4924, 20mg/m^2, intravenously, once on Days 1 and 8; and itraconazole, 200 mg, oral solution, once daily on Days 4-10.
Part B: MLN4924, at a dose previously deemed tolerable given, on Days 1, 3, and 5 of each 21-day Cycle (Study C15010, ClinicalTrails.gov Identifier # NCT01862328) in combination with docetaxel or carboplatin + paclitaxel at standard dose regimen on Day 1 of each 21-day Cycle.
Drug: MLN4924
Drug: Itraconazole
Drug: Docetaxel
Drug: Carboplatin
Drug: Paclitaxel
Interventions
Name
Type
Description
Arm Group Labels
Other Names
MLN4924
Drug
MLN4924 intravenous solution.
MLN4924 + Fluconazole
MLN4924 + Itraconazole
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part A Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Fluconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Fluconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Fluconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Itraconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Itraconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Itraconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Secondary Outcomes
Measure
Description
Time Frame
Part A: Plasma Clearance (CLp) for MLN4924
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
Part A Tmax: Time to Reach the Cmax for MLN4924
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female participants 18 years of age or older.
Must have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is deemed appropriate for treatment with 1 of the 2 chemotherapy regimens in Part B of this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable or measurable.
Recovered (that is, less than or equal to (<=) Grade 1 toxicity) from the effects of prior antineoplastic therapy.
Suitable venous access for the study-required blood sampling for MLN4924 pharmacokinetic (PK) and pharmacodynamic assessments.
Eastern Cooperative Oncology Group performance status (PS) of 0 or 1.
Clinical laboratory values as specified below within 3 days before the first dose of study drug:
Hemoglobin greater than or equal to (>=) 9 gram per deciliter (g/dL)
Absolute neutrophil count >=1,500 per cubic millimeter (/mm^3), not supported by growth factor
Platelet count >=100,000/mm^3
Total bilirubin <=upper limit of normal (ULN)
Prothrombin time (PT) and activated partial thromboplastin time (aPTT) <=1.5*ULN
• For participants to be treated with MLN4924 + docetaxel in Part B, AST and ALT must be <=1.5*ULN, and total bilirubin should be within the normal range.
Serum creatinine <=1.2 mg/dL or calculated/measured creatinine clearance >=50 mL/minute
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, OR
Are surgically sterile, OR
If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through four months after the last dose of study drug, or
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
Male participants, even if surgically sterilized (that is, status postvasectomy), who:
Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
Participants who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male participants) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924.
Exclusion Criteria:
Prior treatment with MLN4924; however, prior treatment with docetaxel, paclitaxel, and carboplatin is allowed.
Treatment with any systemic antineoplastic therapy or investigational products within 21 days before the first dose of study treatment.
Radiotherapy within 14 days before the first dose of study treatment.
Prior treatment with radiation therapy involving >= 25 percent (%) of hematopoietically active bone marrow.
Known hypersensitivity or history of severe intolerance or toxicity to study-assigned chemotherapy. Note: History of severe hypersensitivity reactions to docetaxel (polysorbate 80-based formulations) for participants to be treated with MLN4924 + docetaxel; history of hypersensitivity to carboplatin for participants to be treated with MLN4924 + carboplatin + paclitaxel; or history of severe hypersensitivity to paclitaxel (Cremophor-based formulations) for participants to be treated with MLN4924 + carboplatin + paclitaxel in Part B.
Known hypersensitivity/allergy to fluconazole or itraconazole or their respective excipients.
Systemic treatment with moderate and strong cytochrome P450 (CYP) CYP3A inhibitors or inducers must be discontinued at least 14 days before the first dose of MLN4924. Moderate and strong CYP3A inhibitors and CYP3A inducers are not permitted during the study. Participants must have no history of amiodarone use in the 6 months before the first dose of MLN4924.
Any life-threatening or serious medical or psychiatric illness unrelated to cancer that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Major surgery within 14 days before the first dose of study treatment.
Active uncontrolled infection or severe infectious disease, such as pneumonia, meningitis, septicemia, or methicillin-resistant Staphylococcus aureus infection.
Clinically significant central nervous system disease defined as untreated, progressive, or requiring steroids for control of symptoms.
Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of fluconazole or itraconazole including difficulty swallowing capsules.
Persistent diarrhea (>= Grade 2) lasting greater than (>) 3 days within 2 weeks before the first dose of study treatment.
Known hepatic cirrhosis, hepatitis B surface antigen-positive status, or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (that is, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.
Known human immunodeficiency virus (HIV) positive status.
Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
Uncontrolled high blood pressure (that is, systolic blood pressure >180 millimeter of mercury [mmHg], diastolic blood pressure >95 mmHg).
Left ventricular ejection fraction < 50% as assessed by echocardiogram or radionuclide angiography.
Congestive heart failure New York Heart Association Class III or IV, or Class II with a recent decompensation requiring hospitalization within 4 weeks before screening.
Cardiomyopathy or history of ischemic heart disease.
o Participants with ischemic heart disease who have had acute coronary syndrome (ACS), myocardial infarction (MI), or revascularization (example, coronary artery bypass graft, stent) in the past 6 months are excluded. However, participants with ischemic heart disease who have had ACS, MI, or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll.
Arrhythmia (example, history of polymorphic ventricular fibrillation or torsade de pointes). However, participants with < Grade 3 atrial fibrillation for a period of at least 6 months may enroll. Grade 3 atrial fibrillation is defined as symptomatic and incompletely controlled medically, or controlled with device (example, pacemaker) or ablation, and is excluded. Participants with paroxysmal atrial fibrillation are permitted to enroll.
Prolonged rate corrected QT interval (QTc) >=500 millisecond (msec), calculated according to institutional guidelines.
Implantable cardioverter defibrillator.
Participants with a cardiac pacer whose heart rate is set at a fixed rate and participants on concomitant medication that may limit increase in heart rate in response to hypotension (example, high-dose beta blocker).
Moderate to severe aortic or mitral stenosis or other valvulopathy (ongoing).
Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, pulmonary fibrosis, and pulmonary arterial hypotension.
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 Director Clinical Science
Millennium Pharmaceuticals, Inc.
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Winship Cancer Institute at Emory University
Atlanta
Georgia
30322
United States
Siteman Cancer Center - South County
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Participants with advanced solid tumors were enrolled in this study to receive MLN4924. This study included 2 parts: Part A (drug-drug interaction)- participants received MLN4924 with fluconazole or itraconazole and in Part B (standard of care)- participants received MLN4924 in combination with docetaxel or carboplatin and paclitaxel.
Recruitment Details
Participants took part in the study at 4 investigative site in the United States from 01 April 2014 to 05 June 2017.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
FG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
Periods
Title
Milestones
Reasons Not Completed
Part A: Drug-drug Interaction 2
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
4
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
Apr 12, 2017
Jun 5, 2018
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
Fluconazole
Drug
Fluconazole tablets.
MLN4924 + Fluconazole
Itraconazole
Drug
Itraconazole oral solution.
MLN4924 + Itraconazole
Docetaxel
Drug
Docetaxel intravenous solution.
MLN4924 + Fluconazole
MLN4924 + Itraconazole
Carboplatin
Drug
Carboplatin intravenous solution.
MLN4924 + Fluconazole
MLN4924 + Itraconazole
Paclitaxel
Drug
Paclitaxel intravenous solution.
MLN4924 + Fluconazole
MLN4924 + Itraconazole
Part A: Volume of Distribution (Vz) for MLN4924
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
Part A: Terminal Phase Elimination Half-life (T1/2) for MLN4924
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
Part A: Blood to Plasma (B/P) Concentration Ratio for MLN4924
Day 1 up to 24 hours post infusion
Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Baseline up to 30 days after the last dose of study drug (Day 40 for Part A; approximately Cycle 29 for Part B)
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
Part A: Baseline up to Day 40; Part B: Baseline up to approximately Cycle 29 Day 35
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
Part A: Baseline up to Day 40; Part B: Baseline up to approximately Cycle 29 Day 35
Number of Participants With Clinically Significant Change From Baseline in Body Weight Measurements
Part A: Baseline up to Day 40; Part B: Baseline up to approximately Cycle 29
Part B: Percentage of Participants With Objective Response
Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as complete disappearance of all target lesions. All pathological lymph nodes, both target and non-target, must decrease to normal (short axis less than [<]10 millimeter [mm]). PR was defined as at least 30% decrease under baseline of the sum of diameters of all target lesions.
Baseline up to symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped (approximately Cycle 29)
Part B: Duration of Response
The duration of response was defined in participants with disease response (CR or PR) as the time between the first documentation of response and progressive disease (PD). Responders without PD will be censored at the last clinical assessment of response. CR was defined as complete disappearance of all target lesions. All pathological lymph nodes, both target and non-target, must decrease to normal (short axis <10 mm). PR was defined as at least 30% decrease under baseline of the sum of diameters of all target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time from the date of first documentation of a response and PD (approximately up Cycle 29)
St Louis
Missouri
63110
United States
Sarah Cannon Cancer Center
Nashville
Tennessee
37203
United States
Mary Crowley Medical Research Center
Dallas
Texas
75230
United States
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
FG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
FG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
FG004
Part B: MLN4924 + Docetaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with docetaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
FG005
Part B: MLN4924 + Carboplatin or Paclitaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with carboplatin or paclitaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
FG00013 subjects
FG00113 subjects
FG0026 subjects
FG00319 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
Completed Part A, ongoing to Part B
FG0009 subjects
FG0017 subjects
FG0024 subjects
FG00316 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG0004 subjects
FG0016 subjects
FG0022 subjects
FG0033 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Adverse Event
FG0003 subjects
FG0010 subjects
FG0021 subjects
FG0032 subjects
FG0040 subjects
FG0050 subjects
Other
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Symptomatic Deterioration
FG0001 subjects
FG0015 subjects
FG0020 subjects
FG0031 subjects
FG004
Part B: Standard of Care
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00423 subjects
FG00513 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
The safety population for Part A included all enrolled participants who received at least 1 dose of MLN4924 during Part A.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
BG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
BG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
BG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00013
BG00113
BG0026
BG00319
BG00451
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
BG0007
BG0018
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
Region of Enrollment
Count of Participants
Participants
Title
Denominators
Categories
United States
Title
Measurements
BG00013
BG00113
BG002
Height
Mean
Standard Deviation
centimeter (cm)
Title
Denominators
Categories
Title
Measurements
BG000165.82± 12.142
BG001166.49± 10.023
BG002
Weight
Mean
Standard Deviation
kilogram (kg)
Title
Denominators
Categories
Title
Measurements
BG00071.22± 24.051
BG00164.21± 16.536
BG002
Body Mass Index (BMI)
Mean
Standard Deviation
square meter (m^2)
Title
Denominators
Categories
Title
Measurements
BG0001.792± 0.3405
BG0011.712± 0.2384
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 Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Fluconazole
The pharmacokinetic (PK) evaluable population included all enrolled participants who received all protocol-specified dose regimens within each period during Part A, did not received any excluded medications throughout the completion of PK sampling, and had sufficient MLN4924 plasma concentration-time data to estimate PK parameters.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter (ng/mL)
Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2
MLN4924 8 mg/m^2, infusion, intravenously, once on Day 1.
OG001
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 mg/m^), infusion, intravenously, once on Day 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
Units
Counts
Participants
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG00051.6± 52.3
OG00151.0± 30.8
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric least square (LS) means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference.
Geometric LS Mean Ratio
98.75
2-Sided
90
82.60
118.05
Superiority
Primary
Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Fluconazole
The PK evaluable population included all enrolled participants who received all protocol-specified dose regimens within each period during Part A, did not received any excluded medications throughout the completion of PK sampling, and had sufficient MLN4924 plasma concentration-time data to estimate PK parameters.
Posted
Geometric Mean
Geometric Coefficient of Variation
hour*nanogram per milliliter (h*ng/mL)
Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2
MLN4924 8 mg/m^2, infusion, intravenously, once on Day 1.
OG001
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 mg/m^), infusion, intravenously, once on Day 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
Units
Counts
Participants
Primary
Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Fluconazole
The PK evaluable population included all enrolled participants who received all protocol-specified dose regimens within each period during Part A, did not received any excluded medications throughout the completion of PK sampling, and had sufficient MLN4924 plasma concentration-time data to estimate PK parameters.
Posted
Geometric Mean
Geometric Coefficient of Variation
h*ng/mL
Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2
MLN4924 8 mg/m^2, infusion, intravenously, once on Day 1.
OG001
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 mg/m^), infusion, intravenously, once on Day 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
Units
Counts
Participants
Primary
Part A Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Itraconazole
The PK evaluable population included all enrolled participants who received all protocol-specified dose regimens within each period during Part A, did not received any excluded medications throughout the completion of PK sampling, and had sufficient MLN4924 plasma concentration-time data to estimate PK parameters.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2
MLN4924 8 mg/m^2, infusion, intravenously, once on Day 1.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Day 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2
MLN4924 15 mg/m^2, infusion, intravenously, once on Day 1.
OG003
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
Primary
Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Itraconazole
PK population:enrolled participants who received all protocol-specified dose regimens within each period in Part A,did not receive any excluded medications throughout completion of PK sampling, had sufficient MLN4924 plasma concentration-time data to estimate PK parameters. PK analysis population where data at specified time points were available.
Posted
Geometric Mean
Geometric Coefficient of Variation
h*ng/mL
Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2
MLN4924 8 mg/m^2, infusion, intravenously, once on Day 1.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Day 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2
MLN4924 15 mg/m^2, infusion, intravenously, once on Day 1.
OG003
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
Primary
Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Itraconazole
PK population:enrolled participants who received all protocol-specified dose regimens within each period in Part A,did not receive any excluded medications throughout completion of PK sampling, had sufficient MLN4924 plasma concentration-time data to estimate PK parameters. PK analysis population where data at specified time points were available.
Posted
Geometric Mean
Geometric Coefficient of Variation
h*ng/mL
Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2
MLN4924 8 mg/m^2, infusion, intravenously, once on Day 1.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Day 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2
MLN4924 15 mg/m^2, infusion, intravenously, once on Day 1.
OG003
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
Secondary
Part A: Plasma Clearance (CLp) for MLN4924
PK population:enrolled participants who received all protocol-specified dose regimens within each period in Part A,did not receive any excluded medications throughout completion of PK sampling, had sufficient MLN4924 plasma concentration-time data to estimate PK parameters. PK analysis population where data at specified time points were available.
Posted
Geometric Mean
Geometric Coefficient of Variation
liter per hour (L/h)
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Secondary
Part A Tmax: Time to Reach the Cmax for MLN4924
PK population:enrolled participants who received all protocol-specified dose regimens within each period in Part A,did not receive any excluded medications throughout completion of PK sampling, had sufficient MLN4924 plasma concentration-time data to estimate PK parameters. PK analysis population where data at specified time points were available.
Posted
Median
Full Range
hour
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Secondary
Part A: Volume of Distribution (Vz) for MLN4924
PK population:enrolled participants who received all protocol-specified dose regimens within each period in Part A,did not receive any excluded medications throughout completion of PK sampling, had sufficient MLN4924 plasma concentration-time data to estimate PK parameters. PK analysis population where data at specified time points were available.
Posted
Geometric Mean
Geometric Coefficient of Variation
Liter (L)
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Secondary
Part A: Terminal Phase Elimination Half-life (T1/2) for MLN4924
PK population:enrolled participants who received all protocol-specified dose regimens within each period in Part A,did not receive any excluded medications throughout completion of PK sampling, had sufficient MLN4924 plasma concentration-time data to estimate PK parameters. PK analysis population where data at specified time points were available.
Posted
Geometric Mean
Geometric Coefficient of Variation
hour
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Secondary
Part A: Blood to Plasma (B/P) Concentration Ratio for MLN4924
PK population:enrolled participants who received all protocol-specified dose regimens within each period in Part A,did not receive any excluded medications throughout completion of PK sampling, had sufficient MLN4924 plasma concentration-time data to estimate PK parameters. PK analysis population where data at specified time points were available.
Posted
Geometric Mean
Geometric Coefficient of Variation
Ratio
Day 1 up to 24 hours post infusion
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Secondary
Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
The safety population for Part A included all enrolled participants who received at least 1 dose of MLN4924 during Part A and safety population for Part B included all participants who continued to Part B and received at least 1 dose of study drugs during Part B.
Posted
Count of Participants
Participants
Baseline up to 30 days after the last dose of study drug (Day 40 for Part A; approximately Cycle 29 for Part B)
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Secondary
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
The safety population for Part A included all enrolled participants who received at least 1 dose of MLN4924 during Part A and safety population for Part B included all participants who continued to Part B and received at least 1 dose of study drugs during Part B.
Posted
Count of Participants
Participants
Part A: Baseline up to Day 40; Part B: Baseline up to approximately Cycle 29 Day 35
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Secondary
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
The safety population for Part A included all enrolled participants who received at least 1 dose of MLN4924 during Part A and safety population for Part B included all participants who continued to Part B and received at least 1 dose of study drugs during Part B.
Posted
Count of Participants
Participants
Part A: Baseline up to Day 40; Part B: Baseline up to approximately Cycle 29 Day 35
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Secondary
Number of Participants With Clinically Significant Change From Baseline in Body Weight Measurements
The safety population for Part A included all enrolled participants who received at least 1 dose of MLN4924 during Part A and safety population for Part B included all participants who continued to Part B and received at least 1 dose of study drugs during Part B.
Posted
Number
participants
Part A: Baseline up to Day 40; Part B: Baseline up to approximately Cycle 29
ID
Title
Description
OG000
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
OG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG003
Secondary
Part B: Percentage of Participants With Objective Response
Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as complete disappearance of all target lesions. All pathological lymph nodes, both target and non-target, must decrease to normal (short axis less than [<]10 millimeter [mm]). PR was defined as at least 30% decrease under baseline of the sum of diameters of all target lesions.
The response-evaluable population included all participants who received at least 1 dose of study drug in Part B, had measurable disease as entry criteria for Part B, and had at least 1 postbaseline disease assessment. The response-evaluable population where data at specified time points were available.
Posted
Number
95% Confidence Interval
percentage of participants
Baseline up to symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped (approximately Cycle 29)
ID
Title
Description
OG000
Part B: MLN4924 + Docetaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with docetaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
OG001
Part B: MLN4924 + Carboplatin or Paclitaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with carboplatin or paclitaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
Secondary
Part B: Duration of Response
The duration of response was defined in participants with disease response (CR or PR) as the time between the first documentation of response and progressive disease (PD). Responders without PD will be censored at the last clinical assessment of response. CR was defined as complete disappearance of all target lesions. All pathological lymph nodes, both target and non-target, must decrease to normal (short axis <10 mm). PR was defined as at least 30% decrease under baseline of the sum of diameters of all target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
The response-evaluable population included all participants who received at least 1 dose of study drug in Part B, had measurable disease as entry criteria for Part B, and had at least 1 postbaseline disease assessment. The response-evaluable population where data at specified time points were available.
Posted
Mean
Standard Deviation
months
Time from the date of first documentation of a response and PD (approximately up Cycle 29)
ID
Title
Description
OG000
Part B: MLN4924 + Docetaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with docetaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
OG001
Part B: MLN4924 + Carboplatin or Paclitaxel
Time Frame
Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Day 40 for Part A; approximately Cycle 29 for Part B)
Description
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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: MLN4924 8 mg/m^2 + Fluconazole 400 mg
MLN4924 8 milligram per square meter (mg/m^2), infusion, intravenously, once on Days 1 and 8 along with fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10.
2
13
3
13
13
13
EG001
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg
MLN4924 8 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
3
13
3
13
13
13
EG002
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg
MLN4924 15 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
1
6
2
6
6
6
EG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
2
19
5
19
18
19
EG004
Part B: MLN4924 + Docetaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with docetaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
6
23
14
23
23
23
EG005
Part B: MLN4924 + Carboplatin or Paclitaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with carboplatin or paclitaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
1
13
6
13
13
13
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
ABDOMINAL PAIN
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG0032 affected19 at risk
EG0041 affected23 at risk
EG0050 affected13 at risk
ABDOMINAL PAIN UPPER
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SMALL INTESTINAL OBSTRUCTION
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
OESOPHAGEAL HAEMORRHAGE
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
OBSTRUCTION GASTRIC
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
INTESTINAL OBSTRUCTION
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
UPPER GASTROINTESTINAL HAEMORRHAGE
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
CHOLANGIOCARCINOMA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
OVARIAN CANCER
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PANCREATIC CARCINOMA METASTATIC
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
METASTATIC SQUAMOUS CELL CARCINOMA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SARCOMA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DEEP VEIN THROMBOSIS
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0012 affected13 at risk
EG0020 affected6 at risk
EG003
EMBOLISM
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PNEUMONIA
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
BACTERAEMIA
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
UPPER RESPIRATORY TRACT INFECTIONS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BLOOD CREATININE INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
HYPERKALAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
DYSPNOEA
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
NAUSEA
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
VOMITING
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DIAPHRAGMATIC HERNIA
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
GASTROINTESTINAL PERFORATION
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ASCITES
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PNEUMONIA ASPIRATION
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
RESPIRATORY FAILURE
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SEPTIC SHOCK
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
FAILURE TO THRIVE
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DIABETIC KETOACIDOSIS
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DEHYDRATION
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BREAST CANCER METASTATIC
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
METASTASES TO CENTRAL NERVOUS SYSTEM
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
METASTATIC NEOPLASM
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
NON-SMALL CELL LUNG CANCER
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
OESOPHAGEAL CANCER METASTATIC
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOTENSION
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOVOLAEMIC SHOCK
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ATRIAL FIBRILLATION
Cardiac disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CARDIAC ARREST
Cardiac disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CHEST DISCOMFORT
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
NON-CARDIAC CHEST PAIN
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MUSCULAR WEAKNESS
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SOFT TISSUE NECROSIS
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CEREBRAL HAEMORRHAGE
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SPINAL CORD COMPRESSION
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CUSHING'S SYNDROME
Endocrine disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MENTAL STATUS CHANGES
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ACUTE KIDNEY INJURY
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
ANAEMIA
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0003 affected13 at risk
EG0013 affected13 at risk
EG0022 affected6 at risk
EG0036 affected19 at risk
EG0045 affected23 at risk
EG0054 affected13 at risk
LEUKOPENIA
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
LYMPHADENOPATHY
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
NEUTROPENIA
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
PANCYTOPENIA
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
THROMBOCYTOPENIA
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
IRON DEFICIENCY ANAEMIA
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
LEUKOCYTOSIS
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
LYMPHOPENIA
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
NEUTROPHILIA
Blood and lymphatic system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
TACHYCARDIA
Cardiac disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0012 affected13 at risk
EG0020 affected6 at risk
EG003
SINUS TACHYCARDIA
Cardiac disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ATRIAL FIBRILLATION
Cardiac disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ANGINA PECTORIS
Cardiac disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PALPITATIONS
Cardiac disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PHOTOPHOBIA
Eye disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
VISION BLURRED
Eye disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
EYE ALLERGY
Eye disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
EYE SWELLING
Eye disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
GLAUCOMA
Eye disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
LACRIMATION INCREASED
Eye disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
OCULAR HYPERAEMIA
Eye disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
VISUAL IMPAIRMENT
Eye disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
VOMITING
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0003 affected13 at risk
EG0012 affected13 at risk
EG0021 affected6 at risk
EG003
DIARRHOEA
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0014 affected13 at risk
EG0021 affected6 at risk
EG003
CONSTIPATION
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0003 affected13 at risk
EG0012 affected13 at risk
EG0020 affected6 at risk
EG003
ABDOMINAL PAIN
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0013 affected13 at risk
EG0021 affected6 at risk
EG003
NAUSEA
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0003 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
FLATULENCE
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ABDOMINAL DISTENSION
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
DYSPEPSIA
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
STOMATITIS
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DYSPHAGIA
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ABDOMINAL PAIN LOWER
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ASCITES
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
CHEILITIS
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
DENTAL CARIES
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
GASTROOESOPHAGEAL REFLUX DISEASE
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
HAEMATOCHEZIA
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ORAL PAIN
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
FATIGUE
General disorders
MedDRA (20.0)
Systematic Assessment
EG0003 affected13 at risk
EG0013 affected13 at risk
EG0021 affected6 at risk
EG003
ASTHENIA
General disorders
MedDRA (20.0)
Systematic Assessment
EG0003 affected13 at risk
EG0012 affected13 at risk
EG0020 affected6 at risk
EG003
NON-CARDIAC CHEST PAIN
General disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
OEDEMA PERIPHERAL
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PERIPHERAL SWELLING
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
PYREXIA
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0012 affected13 at risk
EG0020 affected6 at risk
EG003
CATHETER SITE INFLAMMATION
General disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
GAIT DISTURBANCE
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
ILL-DEFINED DISORDER
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
INFLUENZA LIKE ILLNESS
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PAIN
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CHILLS
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MALAISE
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CHEST DISCOMFORT
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
LOCAL SWELLING
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CATHETER SITE ERYTHEMA
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CATHETER SITE PAIN
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
FACE OEDEMA
General disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ABDOMINAL PAIN UPPER
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ANAL INCONTINENCE
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
FAECES DISCOLOURED
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
GASTRITIS
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
GINGIVAL SWELLING
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MOUTH ULCERATION
Gastrointestinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SEASONAL ALLERGY
Immune system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
DRUG HYPERSENSITIVITY
Immune system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
URINARY TRACT INFECTION
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0012 affected13 at risk
EG0020 affected6 at risk
EG003
ORAL HERPES
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
BRONCHITIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ORAL CANDIDIASIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SINUSITIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ABDOMINAL INFECTION
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ANAL ABSCESS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BREAST CELLULITIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CATHETER SITE ABSCESS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CELLULITIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
FUNGAL SKIN INFECTION
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
GASTROENTERITIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PERINEAL ABSCESS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PNEUMONIA
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SCROTAL ABSCESS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
VIRAL UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CATHETER SITE CELLULITIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
CONJUNCTIVITIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
FOLLICULITIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
TINEA PEDIS
Infections and infestations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CONTUSION
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
FALL
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
PUBIS FRACTURE
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
LACERATION
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
INFUSION RELATED REACTION
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
FOOT FRACTURE
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
INCISION SITE COMPLICATION
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
INCISION SITE PAIN
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
LIGAMENT SPRAIN
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SKIN WOUND
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
STOMA SITE IRRITATION
Injury, poisoning and procedural complications
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BLOOD CREATININE INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0002 affected13 at risk
EG0010 affected13 at risk
EG0022 affected6 at risk
EG003
ALANINE AMINOTRANSFERASE INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0012 affected13 at risk
EG0021 affected6 at risk
EG003
ASPARTATE AMINOTRANSFERASE INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0022 affected6 at risk
EG003
BLOOD ALKALINE PHOSPHATASE INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
WEIGHT DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
AMYLASE DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BACTERIAL TEST POSITIVE
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
BLOOD SODIUM DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
BLOOD UREA INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BREATH SOUNDS ABNORMAL
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
FIBRIN D DIMER INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
GAMMA-GLUTAMYLTRANSFERASE INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
LIPASE DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
LIVER FUNCTION TEST INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MICROCOCCUS TEST POSITIVE
Investigations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PANCREATIC ENZYMES DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
WHITE BLOOD CELLS URINE
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
WHITE BLOOD CELL COUNT DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
NEUTROPHIL COUNT DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PLATELET COUNT DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
WHITE BLOOD CELL COUNT INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BLOOD BILIRUBIN INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BLOOD CALCIUM DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BLOOD GLUCOSE INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BLOOD POTASSIUM DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BLOOD THYROID STIMULATING HORMONE DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ELECTROCARDIOGRAM T WAVE INVERSION
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
LYMPHOCYTE COUNT DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
THYROXINE DECREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
WEIGHT INCREASED
Investigations
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DECREASED APPETITE
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0004 affected13 at risk
EG0013 affected13 at risk
EG0021 affected6 at risk
EG003
DEHYDRATION
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0013 affected13 at risk
EG0022 affected6 at risk
EG003
HYPOKALAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0012 affected13 at risk
EG0022 affected6 at risk
EG003
HYPONATRAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0002 affected13 at risk
EG0011 affected13 at risk
EG0021 affected6 at risk
EG003
HYPERGLYCAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0002 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOMAGNESAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOPHOSPHATAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOALBUMINAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOCALCAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOGLYCAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DIABETES MELLITUS
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
FLUID RETENTION
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPERURICAEMIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOPHAGIA
Metabolism and nutrition disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BACK PAIN
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0002 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
PAIN IN EXTREMITY
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0002 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
ARTHRALGIA
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MUSCULAR WEAKNESS
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
FLANK PAIN
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
HAND DEFORMITY
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MUSCULOSKELETAL PAIN
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MYALGIA
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BONE PAIN
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MUSCLE SPASMS
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MUSCULOSKELETAL STIFFNESS
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
JOINT RANGE OF MOTION DECREASED
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MUSCULOSKELETAL CHEST PAIN
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PAIN IN JAW
Musculoskeletal and connective tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
TUMOUR HAEMORRHAGE
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
METASTASES TO CENTRAL NERVOUS SYSTEM
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ORAL NEOPLASM BENIGN
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
TUMOUR ASSOCIATED FEVER
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
TUMOUR PAIN
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HEADACHE
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0003 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DIZZINESS
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0012 affected13 at risk
EG0021 affected6 at risk
EG003
DYSGEUSIA
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOAESTHESIA
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
APHASIA
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DISTURBANCE IN ATTENTION
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
SOMNOLENCE
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
PERIPHERAL SENSORY NEUROPATHY
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
NEUROPATHY PERIPHERAL
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
AMNESIA
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
BURNING SENSATION
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DYSAESTHESIA
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DYSARTHRIA
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
FACIAL PARALYSIS
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MIGRAINE
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
NEURALGIA
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PARAESTHESIA
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PERIPHERAL MOTOR NEUROPATHY
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SINUS HEADACHE
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SPINAL CORD COMPRESSION
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
TREMOR
Nervous system disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ANXIETY
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0012 affected13 at risk
EG0020 affected6 at risk
EG003
CONFUSIONAL STATE
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0021 affected6 at risk
EG003
HALLUCINATION
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
INSOMNIA
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0002 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
AGITATION
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
IRRITABILITY
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
DEPRESSION
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ABNORMAL DREAMS
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MENTAL STATUS CHANGES
Psychiatric disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CHROMATURIA
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
DYSURIA
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
HAEMATURIA
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
POLLAKIURIA
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PROTEINURIA
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
URINARY HESITATION
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
URINARY INCONTINENCE
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
HYDRONEPHROSIS
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
RENAL FAILURE
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
URINARY RETENTION
Renal and urinary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
GENITAL RASH
Reproductive system and breast disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
VAGINAL LESION
Reproductive system and breast disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
VULVOVAGINAL DISCOMFORT
Reproductive system and breast disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DYSPNOEA
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0002 affected13 at risk
EG0011 affected13 at risk
EG0022 affected6 at risk
EG003
COUGH
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0002 affected13 at risk
EG0014 affected13 at risk
EG0020 affected6 at risk
EG003
OROPHARYNGEAL PAIN
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
DYSPNOEA EXERTIONAL
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOXIA
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PARANASAL SINUS HYPERSECRETION
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
RHINORRHOEA
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
UPPER-AIRWAY COUGH SYNDROME
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
WHEEZING
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
EPISTAXIS
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
NASAL CONGESTION
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SINUS CONGESTION
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PHARYNGEAL ERYTHEMA
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PLEURAL EFFUSION
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PRODUCTIVE COUGH
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
RESPIRATORY TRACT CONGESTION
Respiratory, thoracic and mediastinal disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PRURITUS
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DRY SKIN
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
NIGHT SWEATS
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0012 affected13 at risk
EG0020 affected6 at risk
EG003
BLISTER
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DECUBITUS ULCER
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
DERMATITIS ALLERGIC
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ECCHYMOSIS
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ERYTHEMA
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
HYPERHIDROSIS
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ONYCHOMADESIS
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PRURITUS GENERALISED
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
RASH ERYTHEMATOUS
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
RASH MACULAR
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0020 affected6 at risk
EG003
SKIN LESION
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ALOPECIA
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
RASH MACULO-PAPULAR
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
DERMATITIS ACNEIFORM
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
INGROWING NAIL
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
PETECHIAE
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
RASH
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
SKIN DISCOLOURATION
Skin and subcutaneous tissue disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPERTENSION
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected13 at risk
EG0021 affected6 at risk
EG003
HAEMATOMA
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPOTENSION
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
LYMPHOEDEMA
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0021 affected6 at risk
EG003
EMBOLISM
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
FLUSHING
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
ORTHOSTATIC HYPERTENSION
Vascular disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
EAR PAIN
Ear and labyrinth disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
MIDDLE EAR EFFUSION
Ear and labyrinth disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
VERTIGO
Ear and labyrinth disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
CUSHING'S SYNDROME
Endocrine disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
HYPERBILIRUBINAEMIA
Hepatobiliary disorders
MedDRA (20.0)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected13 at risk
EG0020 affected6 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference.
Geometric LS Mean Ratio
110.21
2-Sided
90
102.34
118.69
Superiority
OG000
12
OG00112
Title
Denominators
Categories
Title
Measurements
OG000450± 16.8
OG001498± 15.9
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference.
Geometric LS Mean Ratio
110.66
2-Sided
90
102.53
119.43
Superiority
MLN4924 15 mg/m^2, infusion, intravenously, once on Day 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG004
Part A: MLN4924 20 mg/m^2
MLN4924 20 mg/m^2, infusion, intravenously, once on Day 1.
OG005
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Day 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Units
Counts
Participants
OG00013
OG00113
OG0026
OG0036
OG00414
OG00514
Title
Denominators
Categories
Title
Measurements
OG00059.1± 52.4
OG00166.8± 53.7
OG002121± 61.0
OG003193± 46.9
OG004178± 76.3
OG005137± 29.9
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference.
Geometric LS Mean Ratio
113.05
2-Sided
90
85.35
149.74
Superiority
OG002
OG003
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference
Geometric LS Mean Ratio
159.55
2-Sided
90
89.97
282.96
Superiority
OG004
OG005
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference.
Geometric LS Mean Ratio
77.26
2-Sided
90
55.19
108.17
Superiority
MLN4924 15 mg/m^2, infusion, intravenously, once on Day 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG004
Part A: MLN4924 20 mg/m^2
MLN4924 20 mg/m^2, infusion, intravenously, once on Day 1.
OG005
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Day 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Units
Counts
Participants
OG00013
OG00113
OG0026
OG0036
OG00414
OG00514
Title
Denominators
Categories
Title
Measurements
OG000459± 24.7
OG001571± 23.5
OG002793± 18.2
OG0031030± 17.3
OG0041110± 30.2
OG0051140± 22.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference.
Geometric LS Mean Ratio
121.57
2-Sided
90
110.92
133.24
Superiority
OG002
OG003
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference
Geometric LS Mean Ratio
130.16
2-Sided
90
106.99
158.35
Superiority
OG004
OG005
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference.
Geometric LS Mean Ratio
101.36
2-Sided
90
90.72
113.23
Superiority
MLN4924 15 mg/m^2, infusion, intravenously, once on Day 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG004
Part A: MLN4924 20 mg/m^2
MLN4924 20 mg/m^2, infusion, intravenously, once on Day 1.
OG005
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Day 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Units
Counts
Participants
OG00013
OG00113
OG0026
OG0036
OG00414
OG00514
Title
Denominators
Categories
Title
Measurements
OG000465± 25.1
OG001585± 23.9
OG002798± 18.1
OG0031060± 16.1
OG0041120± 30.4
OG0051130± 23.5
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference.
Geometric LS Mean Ratio
122.95
2-Sided
90
112.13
134.82
Superiority
OG002
OG003
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference
Geometric LS Mean Ratio
130.16
2-Sided
90
106.99
158.35
Superiority
OG004
OG005
Natural-log transformed pharmacokinetic parameters were fit using a mixed effects model with study day as a fixed effect and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed least squares mean and treatment mean difference.
Geometric LS Mean Ratio
100.89
2-Sided
90
91.14
111.68
Superiority
OG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Units
Counts
Participants
OG00012
OG00113
OG0026
OG00314
Title
Denominators
Categories
Day 1
ParticipantsOG00012
ParticipantsOG00113
ParticipantsOG0026
ParticipantsOG00314
Title
Measurements
OG00031.7± 24.9
OG00129.2± 27.5
OG00235.2± 16.3
OG003
Day 8
ParticipantsOG00012
ParticipantsOG00112
ParticipantsOG0026
ParticipantsOG00314
OG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Units
Counts
Participants
OG00012
OG00113
OG0026
OG00314
Title
Denominators
Categories
Day 1
Title
Measurements
OG0001.04(0.93 to 5.00)
OG0011.02(1.00 to 2.77)
OG0021.24(0.97 to 2.17)
OG0031.05(0.97 to 3.08)
Day 8
Title
Measurements
OG0001.21(0.93 to 3.00)
OG0011.50(0.97 to 1.58)
OG0021.03(0.95 to 1.42)
OG003
OG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Units
Counts
Participants
OG00012
OG00113
OG0026
OG00314
Title
Denominators
Categories
Day 1
ParticipantsOG00012
ParticipantsOG00113
ParticipantsOG0026
ParticipantsOG00314
Title
Measurements
OG000503± 29.2
OG001445± 34.3
OG002494± 22.0
OG003
Day 8
ParticipantsOG00012
ParticipantsOG00112
ParticipantsOG0026
ParticipantsOG00314
OG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Units
Counts
Participants
OG00012
OG00113
OG0026
OG00314
Title
Denominators
Categories
Day 1
ParticipantsOG00012
ParticipantsOG00113
ParticipantsOG0026
ParticipantsOG00314
Title
Measurements
OG00011.0± 15.7
OG00110.6± 20.6
OG0029.74± 7.4
OG003
Day 8
ParticipantsOG00012
ParticipantsOG00112
ParticipantsOG0026
ParticipantsOG00314
OG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
Units
Counts
Participants
OG00012
OG00113
OG0026
OG00313
Title
Denominators
Categories
End of infusion
ParticipantsOG00012
ParticipantsOG00113
ParticipantsOG0026
ParticipantsOG00313
Title
Measurements
OG00051.1± 64.1
OG00143.7± 56.9
OG00255.2± 30.4
OG003
2 hours post infusion
ParticipantsOG00012
ParticipantsOG00113
ParticipantsOG0025
ParticipantsOG00313
8 hours post infusion
ParticipantsOG00012
ParticipantsOG00113
ParticipantsOG0025
ParticipantsOG00310
24 hours post infusion
ParticipantsOG00012
ParticipantsOG00113
ParticipantsOG0025
ParticipantsOG00313
OG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG004
Part B: MLN4924 + Docetaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with docetaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
OG005
Part B: MLN4924 + Carboplatin or Paclitaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with carboplatin or paclitaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
Units
Counts
Participants
OG00013
OG00113
OG0026
OG00319
OG00423
OG00513
Title
Denominators
Categories
TEAE
Title
Measurements
OG00013
OG00113
OG0026
OG00318
OG00423
OG00513
SAE
Title
Measurements
OG0003
OG0013
OG0022
OG003
OG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG004
Part B: MLN4924 + Docetaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with docetaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
OG005
Part B: MLN4924 + Carboplatin or Paclitaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with carboplatin or paclitaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
Units
Counts
Participants
OG00013
OG00113
OG0026
OG00319
OG00423
OG00513
Title
Denominators
Categories
Anaemia
Title
Measurements
OG0001
OG0012
OG0020
OG0030
OG0044
OG0052
Aspartate aminotransferase increased
Title
Measurements
OG0000
OG0011
OG0022
OG003
Alanine aminotransferase increased
Title
Measurements
OG0000
OG0011
OG0021
OG003
Blood creatinine increased
Title
Measurements
OG0001
OG0010
OG0021
OG003
Hyponatraemia
Title
Measurements
OG0001
OG0010
OG0020
OG003
Neutropenia
Title
Measurements
OG0000
OG0010
OG0021
OG003
Hypoalbuminaemia
Title
Measurements
OG0001
OG0010
OG0020
OG003
Leukopenia
Title
Measurements
OG0000
OG0011
OG0020
OG003
Gamma-glutamyltransferase increased
Title
Measurements
OG0000
OG0011
OG0020
OG003
Blood urea increased
Title
Measurements
OG0001
OG0010
OG0020
OG003
Liver function test increased
Title
Measurements
OG0000
OG0010
OG0020
OG003
Neutrophil count decreased
Title
Measurements
OG0000
OG0010
OG0020
OG003
Thrombocytopenia
Title
Measurements
OG0000
OG0010
OG0020
OG003
Platelet count decreased
Title
Measurements
OG0000
OG0010
OG0020
OG003
White blood cell count decreased
Title
Measurements
OG0000
OG0010
OG0020
OG003
Pancytopenia
Title
Measurements
OG0000
OG0010
OG0020
OG003
Hypomagnesaemia
Title
Measurements
OG0000
OG0010
OG0020
OG003
Hyperbilirubinaemia
Title
Measurements
OG0000
OG0010
OG0020
OG003
Lymphocyte count decreased
Title
Measurements
OG0000
OG0010
OG0020
OG003
Blood bilirubin increased
Title
Measurements
OG0000
OG0010
OG0020
OG003
Hypophosphataemia
Title
Measurements
OG0000
OG0010
OG0020
OG003
Hypokalaemia
Title
Measurements
OG0000
OG0010
OG0020
OG003
Hyperuricaemia
Title
Measurements
OG0000
OG0010
OG0020
OG003
OG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG004
Part B: MLN4924 + Docetaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with docetaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
OG005
Part B: MLN4924 + Carboplatin or Paclitaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with carboplatin or paclitaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
Units
Counts
Participants
OG00013
OG00113
OG0026
OG00319
OG00423
OG00513
Title
Denominators
Categories
Tachycardia
Title
Measurements
OG0000
OG0012
OG0020
OG0030
OG0045
OG0053
Sinus tachycardia
Title
Measurements
OG0000
OG0010
OG0020
OG003
Hypotension
Title
Measurements
OG0000
OG0010
OG0020
OG003
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg
MLN4924 20 mg/m^2, infusion, intravenously, once on Days 1 and 8 along with itraconazole, 200 mg, solution, orally, once daily on Days 4-10.
OG004
Part B: MLN4924 + Docetaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with docetaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
OG005
Part B: MLN4924 + Carboplatin or Paclitaxel
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with carboplatin or paclitaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.
Units
Counts
Participants
OG00013
OG00113
OG0026
OG00319
OG00423
OG00513
Title
Denominators
Categories
Grade 1 AE: 5 < 10% decrease from baseline
Title
Measurements
OG0000
OG0010
OG0020
OG0031
OG0041
OG0051
Grade 2 AE: 10 - <20% decrease from baseline
Title
Measurements
OG0000
OG0010
OG0020
OG003
Grade 3 AE: >=20% decrease from baseline
Title
Measurements
OG0000
OG0010
OG0020
OG003
Units
Counts
Participants
OG00019
OG0019
Title
Denominators
Categories
Title
Measurements
OG00010.5(1.3 to 33.1)
OG00122.2(2.8 to 60.0)
MLN4924, 8-20 mg/m^2, on Days 1, 3, and 5 along with carboplatin or paclitaxel at standard dose regimen on Day 1 of a 21-day treatment Cycle until symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped.