Study to Evaluate Safety, Pharmacokinetics, and Efficacy... | NCT01526928 | Trialant
NCT01526928
Sponsor
Clovis Oncology, Inc.
Status
Terminated
Last Update Posted
Aug 4, 2020Actual
Enrollment
612Actual
Phase
Phase 1Phase 2
Conditions
Locally Advanced or Metastatic Non Small Cell Lung Cancer
Interventions
Rociletinib
Rociletinib
Rociletinib
Rociletinib
Rociletinib
Rociletinib
Countries
United States
Australia
France
Poland
Protocol Section
Identification Module
NCT ID
NCT01526928
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CO-1686-008
Secondary IDs
Not provided
Brief Title
Study to Evaluate Safety, Pharmacokinetics, and Efficacy of Rociletinib (CO-1686) in Previously Treated Mutant Epidermal Growth Factor Receptor (EGFR) in Non-Small Cell Lung Cancer (NSCLC) Patients
Official Title
A Phase 1/2, Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of Oral Rociletinib in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)
Acronym
Not provided
Organization
Clovis Oncology, Inc.INDUSTRY
Status Module
Record Verification Date
Jul 2020
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 27, 2012Actual
Primary Completion Date
Jul 3, 2018Actual
Completion Date
Aug 27, 2018Actual
First Submitted Date
Jan 31, 2012
First Submission Date that Met QC Criteria
Feb 2, 2012
First Posted Date
Feb 6, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 11, 2019
Results First Submitted that Met QC Criteria
Dec 17, 2019
Results First Posted Date
Jan 6, 2020Actual
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
Jul 26, 2020
Last Update Posted Date
Aug 4, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Clovis Oncology, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
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
Rociletinib is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral rociletinib; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral rociletinib; to assess the safety and efficacy of rociletinib in previously treated NSCLC patients known to have the T790M EGFR mutation.
Detailed Description
Lung cancer remains the most common cancer worldwide with non-small cell lung cancer accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. There are currently no approved therapies for patients who progress on TKIs. Rociletinib may provide an effective therapy for a patient population with few alternative treatment options. Nonclinical data demonstrate that rociletinib inhibits T790M. It is anticipated that rociletinib may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to first generation TKIs.
This is a two-part, open-label study of oral rociletinib administered daily in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or afatinib.
This study will include 2 parts:
Phase 1: Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22
Phase 2: Evaluation of activity and safety in patients with the T790M EGFR mutation who have:
Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR directed therapy received and also had no more than one previous line of chemotherapy or Cohort C - Patients with discordance between local (T790M positive) and central (T790M negative) T790M results, or had no central test result due to inadequacy of the tissue specimen and known to be T790M positive by local test
Conditions Module
Conditions
Locally Advanced or Metastatic Non Small Cell Lung Cancer
Keywords
cancer
metastatic
locally advanced
lung
non-small cell lung cancer
NSCLC
epidermal growth factor receptor
EGFR
T790M
CO-1686
unresectable
recurrent
EGFR-directed therapy
irreversible EGFR inhibitor
TIGER
Rociletinib
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 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
612Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Rociletinib <900 mg BID FB formulation
Experimental
Rociletinib free base (FB) dose <900 mg twice a day (BID)
Drug: Rociletinib
Rociletinib 900 mg BID FB formulation
Experimental
Rociletinib free base (FB) dose 900 mg twice a day (BID)
Drug: Rociletinib
Rociletinib 500 mg BID HBr formulation
Experimental
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID)
Drug: Rociletinib
Rociletinib 625 mg BID HBr formulation
Experimental
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID)
Drug: Rociletinib
Rociletinib 750 mg BID HBr formulation
Experimental
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID)
Drug: Rociletinib
Rociletinib 1000 mg BID HBr formulation
Experimental
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Rociletinib
Drug
Phase 1: Rociletinib <900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles
Rociletinib <900 mg BID FB formulation
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of T790M Positive Patients With Confirmed Response Per Investigator
Percentage of patients with a T790M mutation (determined by central lab) with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment
Duration of Response in patients with a T790M mutation (determined by central lab) with confirmed response per investigator. The DOR for complete response (CR) and partial response (PR) was measured from the date that any of these best responses is first recorded until the first date that progressive disease (PD) is objectively documented. For patients who continue treatment post-progression, the first date of progression was used for the analysis.
Cycle 1 Day 1 to End of Treatment, up to approximately 36 months
Dose Limiting Toxicity (DLT) Incidence
The number of Phase 1 patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.
Cycle 1 Day 1 to Cycle 1 Day 21
Secondary Outcomes
Measure
Description
Time Frame
Overall Survival (OS) Determined by Investigator Assessment
Overall survival was calculated as 1+ the number of days from the first dose of study drug to death due to any cause. Patients without a documented date of death were censored on the date the patient was last known to be alive.
Cycle 1 Day 1 to date of death, assessed up to 42 months
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria -
All patients must meet the following inclusion criteria:
Metastatic or unresectable locally advanced NSCLC
Evidence of a tumor with one or more EGFR mutations excluding exon 20 insertion
Biopsy of either primary or metastatic tumor tissue within 60 days of dosing
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Minimum age of 18 years
Adequate hematological and biological function
Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study-specific evaluation
Phase 2 Cohorts must also meet the following inclusion criteria:
Disease progression confirmed by radiologic assessment while on treatment with EGFR- TKI Or
Disease progression confirmed by radiologic assessment while on treatment with the first single agent EGFR TKI and
Documented evidence of T790M mutation in EGFR following disease progression on the first single agent EGFR TKI.
Measureable disease according to RECIST Version 1.1
Exclusion Criteria -
Any of the following criteria will exclude patients from study participation:
Documented evidence of an Exon 20 insertion activating mutation in the EGFR gene
Active second malignancy
Known pre-existing interstitial lung disease
Patients with Leptomeningeal carcinomatosis are excluded. Other CNS metastases are only permitted if treated, asymptomatic and stable (not requiring steroids for at least 4 weeks prior to start of study treatment).
Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib
Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication before starting rociletinib
Prior treatment with rociletinib or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR
Certain cardiac abnormalities or history
Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib
Females who are pregnant or breastfeeding
Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of rociletinib
Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
Any other reason the investigator considers the patient should not participate in the study
Krug AK, Enderle D, Karlovich C, Priewasser T, Bentink S, Spiel A, Brinkmann K, Emenegger J, Grimm DG, Castellanos-Rizaldos E, Goldman JW, Sequist LV, Soria JC, Camidge DR, Gadgeel SM, Wakelee HA, Raponi M, Noerholm M, Skog J. Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma. Ann Oncol. 2018 Mar 1;29(3):700-706. doi: 10.1093/annonc/mdx765.
There were 612 patients who received rociletinib-111 enrolled in Phase 1 and 501 enrolled in Phase 2. The Phase 1 component of the study was conducted at 8 study sites in the US, Australia, and France. Phase 2 was conducted at 49 study sites in the US, France, Poland, and Australia.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Rociletinib <900 mg BID FB Capsules
Rociletinib free base (FB) dose <900 mg twice a day (BID). FB doses tested ranged from 150 mg once a day (QD) up to 900 mg twice a day (BID). This arm also includes a 400 mg three times a day (TID) dose. Rociletinib FB capsules were administered in Phase 1 only (until November 2013) and were provided in 50 mg or 150 mg white capsules. Patients were instructed to take each dose with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Patients received rociletinib in 21-day treatment cycles and were treated until there was progression by RECIST v1.1, clinical tumor progression, or unacceptable toxicity, or other discontinuation criteria were met. Patients could opt to continue to receive treatment with rociletinib following radiographic progression as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of NSCLC with EGFR-TKIs if the patient provided consent, and the investigator and sponsor approved.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Total
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
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
SAP
No
Yes
No
Statistical Analysis Plan
Jun 12, 2015
Jun 10, 2019
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
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Sequential 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
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID)
Drug: Rociletinib
CO-1686
Rociletinib
Drug
Phase 1: Rociletinib 900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles
Rociletinib 900 mg BID FB formulation
CO-1686
Rociletinib
Drug
Phase 1: Rociletinib 500 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles
Phase 2: Rociletinib 500 mg BID HBr will be administered daily
Rociletinib 500 mg BID HBr formulation
CO-1686
Rociletinib
Drug
Phase 1: Rociletinib 625 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles
Phase 2: Rociletinib 625 mg BID HBr will be administered daily
Rociletinib 625 mg BID HBr formulation
CO-1686
Rociletinib
Drug
Phase 1: Rociletinib 750 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles
Phase 2: Rociletinib 750 mg BID HBr will be administered daily
Rociletinib 750 mg BID HBr formulation
CO-1686
Rociletinib
Drug
Phase 1: Rociletinib 1000 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles
Phase 2: Rociletinib 1000 mg BID HBr will be administered daily
Rociletinib 1000 mg BID HBr formulation
CO-1686
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
Progression-free survival was calculated as the number of days from the date of the first dose of study drug to the date of disease progression or death due to any cause + 1. Patients without a documented event of disease progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment) or date of first dose of study drug if no tumor assessments have been performed. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
PK Profile of Rociletinib - Cmax
Cmax = maximum concentration following administration of rociletinib
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rociletinib - Tmax
Tmax = time to maximum concentration following administration of rociletinib
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rociletinib - AUC 0-24
AUC 0-24 = area under the curve from 0 to 24 hours
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
PK Profile of Rociletinib - T 1/2
T 1/2 = elimination half-life following administration of rociletinib
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
Food Effect on PK of Rociletinib - Cmax
Cmax = maximum concentration following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
Food Effect on PK of Rociletinib - Tmax
Tmax = time to maximum concentration following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
Food Effect on PK of Rociletinib - AUC 0-24
AUC 0-24 = area under the curve from 0 to 24 hours. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
Food Effect on PK of Rociletinib - C24
C24 = rociletinib plasma concentration at 24 hours post the morning dose. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
Food Effect on PK of Rociletinib - T 1/2
T 1/2 = elimination half-life following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
QTcF Values Post Baseline by Daily Dose
Frequency of QT interval prolongation by daily dose (corrected using Fridericia's method, QTcF). To evaluate the effects of rociletinib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Baseline, on Cycle 1 Day 1, Cycle 1 Day 15, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.
Screening to End of Treatment, up to approximately 42 months
QTcF Value Change From Baseline
QTcF value change from baseline by daily dose (corrected using Fridericia's method, QTcF). To evaluate the effects of rociletinib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Baseline, on Cycle 1 Day 1, Cycle 1 Day 15, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.
Screening to End of Treatment, up to approximately 42 months
Objective Response Rate (ORR), Duration of Response (DOR) and Progression-Free Survival (PFS) Per RECIST Version 1.1 as Determined by IRR
Objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS) per RECIST Version 1.1 as determined by independent radiology review (IRR)
Cycle 1 Day 1 to End of Treatment / End of Follow-up
Fountain Valley
California
92708
United States
University of Southern California, Norris Comprehensive Cancer Center
Los Angeles
California
90033
United States
Samuel Oschin Cancer Center
Los Angeles
California
90048
United States
University of California, Irvine
Orange
California
92868
United States
University of California Davis Medical Center
Sacramento
California
95817
United States
UCLA Health System
Santa Monica
California
90404
United States
Stanford Cancer Institute
Stanford
California
94305
United States
East Valley Hematology and Oncology Medical Group, Inc.
Whittier
California
90603
United States
The Oncology Institute of Hope and Innovations
Whittier
California
90603
United States
University of Colorado Anschutz Medical Campus
Aurora
Colorado
80045
United States
Georgetown University Hospital
Washington D.C.
District of Columbia
20007
United States
Sylvester Comprehensive Cancer Center/UMHC
Miami
Florida
33136
United States
Florida Hospital Cancer Institute
Orlando
Florida
32804
United States
University Cancer & Blood Center
Athens
Georgia
30607
United States
University of Chicago Medical Center, The Duchossois Center for Advanced Medicine
Chicago
Illinois
60637
United States
University of Maryland
Baltimore
Maryland
21201
United States
Mass General Hospital
Boston
Massachusetts
02114
United States
Dana Farber Cancer Institute
Boston
Massachusetts
02215
United States
Saint Joseph Mercy Hospital
Ann Arbor
Michigan
48106-0995
United States
Karmanos Cancer Care Institute
Detroit
Michigan
48201
United States
Regional Cancer Care Associates
Morristown
New Jersey
07962
United States
Regional Cancer Center
New Brunswick
New Jersey
07834
United States
Roswell Park Cancer Institute
Buffalo
New York
14263
United States
Monter Cancer Center
Lake Success
New York
11042
United States
Memorial Sloan Kettering Cancer Center
New York
New York
10065
United States
University of Cincinnati Medical Center
Cincinnati
Ohio
45219
United States
Ohio State University, Comprehensive Cancer Center
Columbus
Ohio
43202
United States
Tulsa Cancer Institute
Tulsa
Oklahoma
74146
United States
Providence CancerCenter Oncology and Hematology Care Clinic-Eastside Portland
Portland
Oregon
97213
United States
Perelman Center for Advanced Medicine
Philadelphia
Pennsylvania
19104
United States
University of Pittsburgh Cancer Institute (UPMC), Div. of Medical Oncology
Pittsburgh
Pennsylvania
15232
United States
Vanderbilt University
Nashville
Tennessee
37235
United States
University of Texas Southwestern Medical Center
Dallas
Texas
75390-9179
United States
MD Anderson Cancer Center
Houston
Texas
77030
United States
Huntsman Cancer Institute
Salt Lake City
Utah
84112
United States
Virginia Cancer Specialists, PC
Fairfax
Virginia
22031
United States
Swedish Cancer Institute
Seattle
Washington
98104
United States
University of Washington
Seattle
Washington
98109
United States
Chris O'Brien Lifehouse
Camperdown
New South Wales
2050
Australia
Peter MacCallum Cancer Centre
East Melbourne
Australia
Centre Hospitalier Universitaire de Grenoble
Grenoble
Auvergne-Rhône-Alpes
France
Centre Léon Bérard
Lyon
Auvergne-Rhône-Alpes
France
Centre Antoine Lacassagne
Nice
Provence-Alpes-Côte d'Azur Region
06189
France
Centre François Baclesse
Caen
France
Centre Hospitalier Intercommunal Créteil
Créteil
France
Centre Hospitalier Régional Universitaire de Lille
Lille
France
Institut Gustave Roussy
Villejuif
94805
France
Med University Gdansk
Gdansk
Poland
Derived
Sequist LV, Soria JC, Goldman JW, Wakelee HA, Gadgeel SM, Varga A, Papadimitrakopoulou V, Solomon BJ, Oxnard GR, Dziadziuszko R, Aisner DL, Doebele RC, Galasso C, Garon EB, Heist RS, Logan J, Neal JW, Mendenhall MA, Nichols S, Piotrowska Z, Wozniak AJ, Raponi M, Karlovich CA, Jaw-Tsai S, Isaacson J, Despain D, Matheny SL, Rolfe L, Allen AR, Camidge DR. Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1700-9. doi: 10.1056/NEJMoa1413654.
FG001
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID). Rociletinib FB capsules were administered in Phase 1 only (until November 2013) and were provided in 50 mg or 150 mg white capsules. Patients were instructed to take each dose with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Patients received rociletinib in 21-day treatment cycles and were treated until there was progression by RECIST v1.1, clinical tumor progression, or unacceptable toxicity, or other discontinuation criteria were met. Patients could opt to continue to receive treatment with rociletinib following radiographic progression as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of NSCLC with EGFR-TKIs if the patient provided consent, and the investigator and sponsor approved.
FG002
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID). Rociletinib hydrobromide (HBr) tablets were administered in Phase 1 (starting in August 2013) and in all Phase 2 cohorts and were provided in 50 mg or 150 mg white capsules. Patients were instructed to take each dose with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Patients received rociletinib in 21-day cycles and were treated until there was progression by RECIST v1.1, clinical tumor progression, or unacceptable toxicity, or other discontinuation criteria were met. Patients could opt to continue to receive treatment with rociletinib following radiographic progression as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of NSCLC with EGFR-TKIs if the patient provided consent, and the investigator and sponsor approved.
FG003
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID). Rociletinib hydrobromide (HBr) tablets were administered in Phase 1 (starting in August 2013) and in all Phase 2 cohorts and were provided in 50 mg or 150 mg white capsules. Patients were instructed to take each dose with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Patients received rociletinib in 21-day cycles and were treated until there was progression by RECIST v1.1, clinical tumor progression, or unacceptable toxicity, or other discontinuation criteria were met. Patients could opt to continue to receive treatment with rociletinib following radiographic progression as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of NSCLC with EGFR-TKIs if the patient provided consent, and the investigator and sponsor approved.
FG004
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID). Rociletinib hydrobromide (HBr) tablets were administered in Phase 1 (starting in August 2013) and in all Phase 2 cohorts and were provided in 50 mg or 150 mg white capsules. Patients were instructed to take each dose with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Patients received rociletinib in 21-day cycles and were treated until there was progression by RECIST v1.1, clinical tumor progression, or unacceptable toxicity, or other discontinuation criteria were met. Patients could opt to continue to receive treatment with rociletinib following radiographic progression as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of NSCLC with EGFR-TKIs if the patient provided consent, and the investigator and sponsor approved.
FG005
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID). Rociletinib hydrobromide (HBr) tablets were administered in Phase 1 (starting in August 2013) and in all Phase 2 cohorts and were provided in 50 mg or 150 mg white capsules. Patients were instructed to take each dose with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Patients received rociletinib in 21-day cycles and were treated until there was progression by RECIST v1.1, clinical tumor progression, or unacceptable toxicity, or other discontinuation criteria were met. Patients could opt to continue to receive treatment with rociletinib following radiographic progression as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of NSCLC with EGFR-TKIs if the patient provided consent, and the investigator and sponsor approved.
FG00038 subjects
FG00119 subjects
FG002209 subjects
FG003245 subjects
FG00495 subjects
FG0056 subjects
Started Phase 1
Upon completion of Cycle 1, Phase 1 pts could participate in an optional Treatment-extension Period
FG00038 subjects
FG00119 subjects
FG00218 subjects
FG00317 subjects
FG00413 subjects
FG0056 subjects
Started Phase 2
FG0000 subjects
FG0010 subjects
FG002191 subjects
FG003228 subjects
FG00482 subjects
FG0050 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG00038 subjects
FG00119 subjects
FG002209 subjects
FG003245 subjects
FG00495 subjects
FG0056 subjects
Type
Comment
Reasons
Progressive Disease
FG00035 subjects
FG00117 subjects
FG002150 subjects
FG003182 subjects
FG00476 subjects
FG0054 subjects
Adverse Event
FG0002 subjects
FG0011 subjects
FG00229 subjects
FG00340 subjects
FG004
Death
FG0000 subjects
FG0010 subjects
FG0023 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
FG00213 subjects
FG00311 subjects
FG004
Physician Decision
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0035 subjects
FG004
Other Reason
FG0000 subjects
FG0011 subjects
FG00211 subjects
FG0034 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Protocol Deviation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG004
Missing
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Rociletinib <900 mg BID FB Capsules
Rociletinib free base (FB) dose <900 mg twice a day (BID).
BG001
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
BG002
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
BG003
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
BG004
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
BG005
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00038
BG00119
BG002209
BG003245
BG00495
BG0056
BG006612
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002209
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
White
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002
Time Since Diagnosis of NSCLC (months)
Data not available for one participant in the 500 mg BID Hbr treatment group.
Mean
Standard Deviation
Months
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002
T790M Status ( Determined by Central Lab)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002
History of CNS Metastases
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002
Number of Previous Therapies
Mean
Standard Deviation
Therapies
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002
Number of Previous TKI Therapies
Mean
Standard Deviation
Therapies
Title
Denominators
Categories
ParticipantsBG00038
ParticipantsBG00119
ParticipantsBG002
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
Percentage of T790M Positive Patients With Confirmed Response Per Investigator
Percentage of patients with a T790M mutation (determined by central lab) with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Intent-to-treat: All randomized patients who are confirmed by central lab to be T790M positive
Posted
Count of Participants
Participants
Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
ID
Title
Description
OG000
Rociletinib <900 mg BID FB Capsules
Rociletinib free base (FB) dose <900 mg twice a day (BID).
OG001
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
OG002
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
OG003
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
OG004
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
OG005
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).
Units
Counts
Participants
OG00023
OG0019
OG002188
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0013
OG00254
OG003
Primary
Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment
Duration of Response in patients with a T790M mutation (determined by central lab) with confirmed response per investigator. The DOR for complete response (CR) and partial response (PR) was measured from the date that any of these best responses is first recorded until the first date that progressive disease (PD) is objectively documented. For patients who continue treatment post-progression, the first date of progression was used for the analysis.
The DOR was measured only in T790M positive patients with a Complete Response (CR) or Partial Response (PR). There were no responders in the Rociletinib <900 mg BID treatment group so DOR is not applicable and thus not reported.
Posted
Median
95% Confidence Interval
Days
Cycle 1 Day 1 to End of Treatment, up to approximately 36 months
ID
Title
Description
OG000
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID)
OG001
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID)
OG002
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID)
Primary
Dose Limiting Toxicity (DLT) Incidence
The number of Phase 1 patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.
The dose limiting toxicity (DLT) evaluable population includes all patients who have completed Cycle 1, and who were enrolled while the dose escalation (Phase 1) part of the study was ongoing.
Posted
Count of Participants
Participants
Cycle 1 Day 1 to Cycle 1 Day 21
ID
Title
Description
OG000
Rociletinib <900 mg BID FB Capsules
Rociletinib free base (FB) dose <900 mg twice a day (BID).
OG001
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
OG002
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
OG003
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
Secondary
Overall Survival (OS) Determined by Investigator Assessment
Overall survival was calculated as 1+ the number of days from the first dose of study drug to death due to any cause. Patients without a documented date of death were censored on the date the patient was last known to be alive.
The overall number of patients analyzed contains centrally determined T790M positive patients only. There are 2 less patients in the <900 mg BID FB group, and 1 less patient in each of the 500, 625 and 750 mg BID dose groups because they were not followed for OS.
Posted
Median
95% Confidence Interval
months
Cycle 1 Day 1 to date of death, assessed up to 42 months
ID
Title
Description
OG000
Rociletinib <900 mg BID FB Capsules
Rociletinib free base (FB) dose <900 mg twice a day (BID)
OG001
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID)
OG002
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID)
OG003
Rociletinib 625 mg BID HBr Tablets
Secondary
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
Progression-free survival was calculated as the number of days from the date of the first dose of study drug to the date of disease progression or death due to any cause + 1. Patients without a documented event of disease progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment) or date of first dose of study drug if no tumor assessments have been performed. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
The overall number of patients analyzed contains centrally determined T790M positive patients only. There are 2 less patients in the <900 mg BID FB group, and 1 less patient in each of the 500 and 625 mg BID dose groups because they were not followed for PFS.
Posted
Median
95% Confidence Interval
months
Cycle 1 Day 1 to End of Treatment, up to approximately 42 months
ID
Title
Description
OG000
Rociletinib <900 mg BID FB Capsules
Rociletinib free base (FB) dose <900 mg twice a day (BID)
OG001
Rociletinib 900 mg BID FB Capsules
Secondary
PK Profile of Rociletinib - Cmax
Cmax = maximum concentration following administration of rociletinib
PK parameters were assessed in a subset of patients treated with rociletinib. For some parameters, the number analyzed at Day 1 and Day 15 differs from the overall number analyzed based on the number of evaluable samples collected at each time point.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
ID
Title
Description
OG000
Rociletinib 150 mg QD FB Capsules
Rociletinib free base (FB) dose 150 mg once a day (QD).
OG001
Rociletinib 200 mg QD FB Capsules
Rociletinib free base (FB) dose 200 mg once a day (QD).
OG002
Rociletinib 300 mg QD FB Capsules
Rociletinib free base (FB) dose 300 mg once a day (QD).
OG003
Rociletinib 450 mg QD FB Capsules
Rociletinib free base (FB) dose 450 mg once a day (QD).
Secondary
PK Profile of Rociletinib - Tmax
Tmax = time to maximum concentration following administration of rociletinib
PK parameters were assessed in a subset of patients treated with rociletinib. For some parameters, the number analyzed at Day 1 and Day 15 differs from the overall number analyzed based on the number of evaluable samples collected at each time point.
Posted
Median
Full Range
Hours
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
ID
Title
Description
OG000
Rociletinib 150 mg QD FB Capsules
Rociletinib free base (FB) dose 150 mg once a day (QD).
OG001
Rociletinib 200 mg QD FB Capsules
Rociletinib free base (FB) dose 200 mg once a day (QD).
OG002
Rociletinib 300 mg QD FB Capsules
Rociletinib free base (FB) dose 300 mg once a day (QD).
OG003
Rociletinib 450 mg QD FB Capsules
Rociletinib free base (FB) dose 450 mg once a day (QD).
Secondary
PK Profile of Rociletinib - AUC 0-24
AUC 0-24 = area under the curve from 0 to 24 hours
PK parameters were assessed in a subset of patients treated with rociletinib. For some parameters, the number analyzed at Day 1 and Day 15 differs from the overall number analyzed based on the number of evaluable samples collected at each time point. AUC was not calculated for patients in the 400 mg TID treatment group.
Posted
Mean
Standard Deviation
ng*hr/mL
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
ID
Title
Description
OG000
Rociletinib 150 mg QD FB Capsules
Rociletinib free base (FB) dose 150 mg once a day (QD).
OG001
Rociletinib 200 mg QD FB Capsules
Rociletinib free base (FB) dose 200 mg once a day (QD).
OG002
Rociletinib 300 mg QD FB Capsules
Rociletinib free base (FB) dose 300 mg once a day (QD).
OG003
Rociletinib 450 mg QD FB Capsules
Rociletinib free base (FB) dose 450 mg once a day (QD).
Secondary
PK Profile of Rociletinib - T 1/2
T 1/2 = elimination half-life following administration of rociletinib
PK parameters were assessed in a subset of patients treated with rociletinib. For some parameters, the number analyzed at Day 1 and Day 15 differs from the overall number analyzed based on the number of evaluable samples collected at each time point. Elimination half-life was not calculated for patients in the 400 mg TID treatment group.
Posted
Mean
Standard Deviation
Hours
Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
ID
Title
Description
OG000
Rociletinib 150 mg QD FB Capsules
Rociletinib free base (FB) dose 150 mg once a day (QD).
OG001
Rociletinib 200 mg QD FB Capsules
Rociletinib free base (FB) dose 200 mg once a day (QD).
OG002
Rociletinib 300 mg QD FB Capsules
Rociletinib free base (FB) dose 300 mg once a day (QD).
OG003
Rociletinib 450 mg QD FB Capsules
Rociletinib free base (FB) dose 450 mg once a day (QD).
Secondary
Food Effect on PK of Rociletinib - Cmax
Cmax = maximum concentration following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
A subset of 3 patients treated with rociletinib 150 mg FB capsules
Posted
Mean
Standard Deviation
ng/mL
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
ID
Title
Description
OG000
Cmax Fasting
Rociletinib 150 mg FB single dose given while fasting
OG001
Cmax Fed
Rociletinib 150 mg FB single dose given with a high-fat breakfast
Units
Counts
Participants
Secondary
Food Effect on PK of Rociletinib - Tmax
Tmax = time to maximum concentration following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
A subset of 3 patients treated with rociletinib 150 mg FB capsules
Posted
Median
Full Range
Hours
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
ID
Title
Description
OG000
Tmax Fasting
Rociletinib 150 mg FB single dose given while fasting
OG001
Tmax Fed
Rociletinib 150 mg FB single dose given with a high-fat breakfast
Units
Counts
Participants
Secondary
Food Effect on PK of Rociletinib - AUC 0-24
AUC 0-24 = area under the curve from 0 to 24 hours. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
A subset of 3 patients treated with rociletinib 150 mg FB capsules. AUC could not be determined for 1 patient in the Fed arm.
Posted
Mean
Standard Deviation
ng*hr/mL
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
ID
Title
Description
OG000
AUC 0-24 Fasting
Rociletinib 150 mg FB single dose given while fasting
OG001
AUC 0-24 Fed
Rociletinib 150 mg FB single dose given with a high-fat breakfast
Units
Counts
Participants
Secondary
Food Effect on PK of Rociletinib - C24
C24 = rociletinib plasma concentration at 24 hours post the morning dose. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
A subset of 3 patients treated with rociletinib 150 mg FB capsules
Posted
Mean
Standard Deviation
ng/mL
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
ID
Title
Description
OG000
C24 Fasting
Rociletinib 150 mg FB single dose given while fasting
OG001
C24 Fed
Rociletinib 150 mg FB single dose given with a high-fat breakfast
Units
Counts
Participants
Secondary
Food Effect on PK of Rociletinib - T 1/2
T 1/2 = elimination half-life following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
A subset of 3 patients treated with rociletinib 150 mg FB capsules. Data did not allow the calculation of half-life with high fat mean in 2 patients.
Posted
Mean
Standard Deviation
Hours
Day -7 prior to Cycle 1 Day 1, or approximately 7 days
ID
Title
Description
OG000
T 1/2 Fasting
Rociletinib 150 mg FB single dose given while fasting
OG001
T 1/2 Fed
Rociletinib 150 mg FB single dose given with a high-fat breakfast
Units
Counts
Participants
Secondary
QTcF Values Post Baseline by Daily Dose
Frequency of QT interval prolongation by daily dose (corrected using Fridericia's method, QTcF). To evaluate the effects of rociletinib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Baseline, on Cycle 1 Day 1, Cycle 1 Day 15, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.
Safety population by daily dose
Posted
Count of Participants
Participants
Screening to End of Treatment, up to approximately 42 months
ID
Title
Description
OG000
Rociletinib <900 mg BID FB Capsules
Rociletinib free base (FB) dose <900 mg twice a day (BID).
OG001
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
OG002
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
OG003
Rociletinib 625 mg BID HBr Tablets
Secondary
QTcF Value Change From Baseline
QTcF value change from baseline by daily dose (corrected using Fridericia's method, QTcF). To evaluate the effects of rociletinib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Baseline, on Cycle 1 Day 1, Cycle 1 Day 15, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.
Safety population by daily dose
Posted
Count of Participants
Participants
Screening to End of Treatment, up to approximately 42 months
ID
Title
Description
OG000
Rociletinib <900 mg BID FB Capsules
Rociletinib free base (FB) dose <900 mg twice a day (BID).
OG001
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
OG002
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
OG003
Rociletinib 625 mg BID HBr Tablets
Secondary
Objective Response Rate (ORR), Duration of Response (DOR) and Progression-Free Survival (PFS) Per RECIST Version 1.1 as Determined by IRR
Objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS) per RECIST Version 1.1 as determined by independent radiology review (IRR)
Tumor scans were collected for independent evaluation, however ORR, DOR and PFS analyses were not performed by the central reader since the sponsor deemed not necessary following early study termination. Therefore, all IRR outcome measures were not collected and can not be reported.
Posted
Cycle 1 Day 1 to End of Treatment / End of Follow-up
ID
Title
Description
OG000
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
OG001
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
Units
Counts
Participants
OG000
Time Frame
Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug, or up to approximately 42 months. In addition, study procedure-related AEs that occur after signing of the informed consent form and before first dose of study drug were expected to be reported. Any Serious Adverse Events or Adverse Events of Special Interest were followed until resolution or stabilization, or until patient is lost to follow-up.
Description
If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class).
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
Rociletinib <900 mg BID FB Capsules
Rociletinib free base (FB) dose <900 mg twice a day (BID).
4
38
14
38
37
38
EG001
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
4
19
8
19
19
19
EG002
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
31
209
106
209
208
209
EG003
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
40
245
138
245
244
245
EG004
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
19
95
54
95
95
95
EG005
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).
3
6
5
6
6
6
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0024 affected209 at risk
EG0032 affected245 at risk
EG0042 affected95 at risk
EG0050 affected6 at risk
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Atrial tachycardia
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Atrioventricular block complete
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Palpitations
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Pericarditis
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Supraventricular tachycardia
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Torsade de pointes
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Ventricular tachyarrhythmia
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Adrenal insufficiency
Endocrine disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Inappropriate antidiuretic hormone secretion
Endocrine disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Cataract
Eye disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0022 affected209 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Intestinal dilatation
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Intestinal Obstruction
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Large intestinal obstruction
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Mallory-Weiss syndrome
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Melaena
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG0025 affected209 at risk
EG003
Oesophagitis
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0025 affected209 at risk
EG003
Pancreatitis acute
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Small intestinal perforation
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Subileus
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG0027 affected209 at risk
EG003
Asthenia
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Fatigue
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
General physical health deterioration
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Oedema peripheral
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pain
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pyrexia
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0024 affected209 at risk
EG003
Sudden death
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Bile duct obstruction
Hepatobiliary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Bile duct stone
Hepatobiliary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Hepatic pain
Hepatobiliary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Liver injury
Hepatobiliary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Arthritis bacterial
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Bacteraemia
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Clostridium difficile infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Device related infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Endocarditis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hepatic infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Influenza
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Liver abscess
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Lung infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG0027 affected209 at risk
EG003
Pneumonia bacterial
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pneumonia influenzal
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Postoperative wound infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Sepsis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG0024 affected209 at risk
EG003
Septic shock
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Serratia bacteraemia
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Staphylococcal bacteraemia
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0023 affected209 at risk
EG003
Urosepsis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Hip fracture
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Jaw fracture
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Radiation necrosis
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Radiation pneumonitis
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Subcutaneous haematoma
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Subdural haemorrhage
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Electrocardiogram T wave inversion
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
General physical condition abnormal
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Lipase increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Transaminases increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Troponin increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Diabetic ketoacidosis
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0024 affected209 at risk
EG003
Failure to thrive
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Fluid overload
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Glucose tolerance impaired
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG00221 affected209 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0025 affected209 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Chondrocalcinosis pyrophosphate
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pathological fracture
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Spinal pain
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Cancer pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Malignant neoplasm progression
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (18.0)
Systematic Assessment
EG0008 affected38 at risk
EG0015 affected19 at risk
EG00225 affected209 at risk
EG003
Malignant pleural infusion
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Metastases to central nervous system
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Metastases to skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Neoplasm malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Transitional cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Basilar artery thrombosis
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Brain oedema
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0023 affected209 at risk
EG003
Coma
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Disturbance in attention
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Headache
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Presyncope
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Seizure
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Spinal cord oedema
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Status epilepticus
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Syncope
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Hallucination
Psychiatric disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Mental status changes
Psychiatric disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pelvic pain
Reproductive system and breast disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Vaginal haemorrhage
Reproductive system and breast disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Acute respiratory distress syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0028 affected209 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Lung disorder
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Pleuritic pain
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pneumonia aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0023 affected209 at risk
EG003
Pulmonary fibrosis
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pulmonary haemorrhage
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Pulmonary hypertension
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Respiratory distress
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hypotension
Vascular disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Subgaleal haematoma
Vascular disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Venous thrombosis
Vascular disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (18.0)
Systematic Assessment
EG0005 affected38 at risk
EG0013 affected19 at risk
EG00247 affected209 at risk
EG00374 affected245 at risk
EG00419 affected95 at risk
EG0051 affected6 at risk
Increased tendency to bruise
Blood and lymphatic system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG0021 affected209 at risk
EG003
Leukocytosis
Blood and lymphatic system disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG0023 affected209 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG0028 affected209 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0029 affected209 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG00210 affected209 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0013 affected19 at risk
EG00221 affected209 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG00210 affected209 at risk
EG003
Deafness unilateral
Ear and labyrinth disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Dysacusis
Ear and labyrinth disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Cataract
Eye disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG00216 affected209 at risk
EG003
Diplopia
Eye disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0022 affected209 at risk
EG003
Dry eye
Eye disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0024 affected209 at risk
EG003
Lacrimation increased
Eye disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Vision blurred
Eye disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG00213 affected209 at risk
EG003
Visual acuity reduced
Eye disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0024 affected209 at risk
EG003
Visual impairment
Eye disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0025 affected209 at risk
EG003
Vitreous floaters
Eye disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0023 affected209 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0028 affected209 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0014 affected19 at risk
EG00225 affected209 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG00215 affected209 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0009 affected38 at risk
EG0012 affected19 at risk
EG00242 affected209 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0008 affected38 at risk
EG00111 affected19 at risk
EG002121 affected209 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG00226 affected209 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0012 affected19 at risk
EG0027 affected209 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0023 affected209 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG00222 affected209 at risk
EG003
Gingival bleeding
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0022 affected209 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG0021 affected209 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG00014 affected38 at risk
EG00111 affected19 at risk
EG00295 affected209 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0025 affected209 at risk
EG003
Retching
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0023 affected209 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (18.0)
Systematic Assessment
EG0009 affected38 at risk
EG0016 affected19 at risk
EG00265 affected209 at risk
EG003
Asthenia
General disorders
MedDRA (18.0)
Systematic Assessment
EG0006 affected38 at risk
EG0011 affected19 at risk
EG00228 affected209 at risk
EG003
Catheter site pain
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Chills
General disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0026 affected209 at risk
EG003
Face oedema
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Fatigue
General disorders
MedDRA (18.0)
Systematic Assessment
EG0009 affected38 at risk
EG0018 affected19 at risk
EG002109 affected209 at risk
EG003
Feeling abnormal
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Feeling cold
General disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Gait disturbance
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0013 affected19 at risk
EG0028 affected209 at risk
EG003
Influenza like illness
General disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0025 affected209 at risk
EG003
Malaise
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0025 affected209 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0011 affected19 at risk
EG0029 affected209 at risk
EG003
Oedema peripheral
General disorders
MedDRA (18.0)
Systematic Assessment
EG0004 affected38 at risk
EG0011 affected19 at risk
EG00240 affected209 at risk
EG003
Pain
General disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0027 affected209 at risk
EG003
Pyrexia
General disorders
MedDRA (18.0)
Systematic Assessment
EG0004 affected38 at risk
EG0012 affected19 at risk
EG00219 affected209 at risk
EG003
Temperature intolerance
General disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0022 affected209 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0011 affected19 at risk
EG0026 affected209 at risk
EG003
Jaundice
Hepatobiliary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Bacterial disease carrier
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Candida infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Clostridium difficile infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Cystitis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0023 affected209 at risk
EG003
Eye infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Folliculitis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0026 affected209 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0011 affected19 at risk
EG00212 affected209 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG0021 affected209 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0026 affected209 at risk
EG003
Tooth infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0022 affected209 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0012 affected19 at risk
EG00223 affected209 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG00227 affected209 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0013 affected19 at risk
EG00214 affected209 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG0029 affected209 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Hip fracture
Injury, poisoning and procedural complications
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0013 affected19 at risk
EG00219 affected209 at risk
EG003
Amylase increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0004 affected38 at risk
EG0014 affected19 at risk
EG00221 affected209 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0004 affected38 at risk
EG0011 affected19 at risk
EG00213 affected209 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0014 affected19 at risk
EG00216 affected209 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG00213 affected209 at risk
EG003
Blood glucose increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0024 affected209 at risk
EG003
Blood phosphorus decreased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Blood urine present
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0013 affected19 at risk
EG00261 affected209 at risk
EG003
Electrocardiogram T wave abnormal
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Glycosylated haemoglobin increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0022 affected209 at risk
EG003
Insulin C-peptide increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0022 affected209 at risk
EG003
Lipase increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0023 affected209 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG00212 affected209 at risk
EG003
Neutrophil count increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0022 affected209 at risk
EG003
Platelet count decreased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG00220 affected209 at risk
EG003
QRS axis abnormal
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Transaminases increased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG0025 affected209 at risk
EG003
Weight decreased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0004 affected38 at risk
EG0014 affected19 at risk
EG00259 affected209 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0010 affected19 at risk
EG00219 affected209 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0009 affected38 at risk
EG00110 affected19 at risk
EG00280 affected209 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0014 affected19 at risk
EG00221 affected209 at risk
EG003
Glucose tolerance impaired
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0026 affected209 at risk
EG003
Gout
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0004 affected38 at risk
EG00110 affected19 at risk
EG002113 affected209 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0027 affected209 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0012 affected19 at risk
EG00218 affected209 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0026 affected209 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG00227 affected209 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG00225 affected209 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG00225 affected209 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0005 affected38 at risk
EG0013 affected19 at risk
EG00223 affected209 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0006 affected38 at risk
EG0013 affected19 at risk
EG00226 affected209 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG0024 affected209 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0025 affected209 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0004 affected38 at risk
EG0016 affected19 at risk
EG00257 affected209 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0029 affected209 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0012 affected19 at risk
EG00212 affected209 at risk
EG003
Musculoskeletal discomfort
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0008 affected38 at risk
EG0011 affected19 at risk
EG00220 affected209 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0005 affected38 at risk
EG0014 affected19 at risk
EG00223 affected209 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0010 affected19 at risk
EG00214 affected209 at risk
EG003
Malignant neoplasm progression
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (18.0)
Systematic Assessment
EG00011 affected38 at risk
EG0015 affected19 at risk
EG00228 affected209 at risk
EG003
Ageusia
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Amnesia
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0024 affected209 at risk
EG003
Ataxia
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Balance disorder
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Disturbance in attention
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0004 affected38 at risk
EG0014 affected19 at risk
EG00225 affected209 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG0020 affected209 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0012 affected19 at risk
EG00217 affected209 at risk
EG003
Headache
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0006 affected38 at risk
EG0015 affected19 at risk
EG00257 affected209 at risk
EG003
Hemiparesis
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0023 affected209 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0013 affected19 at risk
EG0025 affected209 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0025 affected209 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG00210 affected209 at risk
EG003
Restless legs syndrome
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Seizure
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Tension headache
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Tremor
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0013 affected19 at risk
EG0027 affected209 at risk
EG003
Vocal cord paralysis
Nervous system disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG00219 affected209 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0028 affected209 at risk
EG003
Depression
Psychiatric disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0013 affected19 at risk
EG0028 affected209 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (18.0)
Systematic Assessment
EG0004 affected38 at risk
EG0012 affected19 at risk
EG00219 affected209 at risk
EG003
Micturition urgency
Renal and urinary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0028 affected209 at risk
EG003
Renal impairment
Renal and urinary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Urge incontinence
Renal and urinary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Urinary tract disorder
Renal and urinary disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Apnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0009 affected38 at risk
EG0013 affected19 at risk
EG00262 affected209 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0011 affected19 at risk
EG0024 affected209 at risk
EG003
Dypnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG00010 affected38 at risk
EG0012 affected19 at risk
EG00251 affected209 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0010 affected19 at risk
EG00212 affected209 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0012 affected19 at risk
EG0027 affected209 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0023 affected209 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0012 affected19 at risk
EG0026 affected209 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0026 affected209 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG0028 affected209 at risk
EG003
Paranasal sinus hypersecretion
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG0021 affected209 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0012 affected19 at risk
EG0026 affected209 at risk
EG003
Pleuritic pain
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0012 affected19 at risk
EG0021 affected209 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0025 affected209 at risk
EG003
Pulmonary hypertension
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Respiratory distress
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0022 affected209 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Throat tightness
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0021 affected209 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0024 affected209 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG00213 affected209 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0013 affected19 at risk
EG00214 affected209 at risk
EG003
Photosensitivity reaction
Skin and subcutaneous tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Pruritis
Skin and subcutaneous tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0001 affected38 at risk
EG0011 affected19 at risk
EG0025 affected209 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0003 affected38 at risk
EG0012 affected19 at risk
EG00217 affected209 at risk
EG003
Rash morbilliform
Skin and subcutaneous tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0020 affected209 at risk
EG003
Skin erosion
Skin and subcutaneous tissue disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Flushing
Vascular disorders
MedDRA (18.0)
Systematic Assessment
EG0002 affected38 at risk
EG0010 affected19 at risk
EG0020 affected209 at risk
EG003
Hypertension
Vascular disorders
MedDRA (18.0)
Systematic Assessment
EG0005 affected38 at risk
EG0010 affected19 at risk
EG00216 affected209 at risk
EG003
Hypotension
Vascular disorders
MedDRA (18.0)
Systematic Assessment
EG0000 affected38 at risk
EG0011 affected19 at risk
EG0024 affected209 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
All parties agree to submit all manuscripts or abstracts to all other parties 30 days prior to submission. This will enable all parties to protect proprietary information and to provide comments based on information that may not yet be available to other parties. The sponsor may request a delay in publication if there are important intellectual property concerns relating to publication, but does not have the right to suppress publication of the study results indefinitely.
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID)
OG004
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID)
Units
Counts
Participants
OG0003
OG00154
OG00272
OG00323
OG0043
Title
Denominators
Categories
Title
Measurements
OG000329.0(190.0 to 713.0)
OG001275.0(226.0 to 336.0)
OG002274.0(169.0 to 337.0)
OG003217.0(146.0 to 340.0)
OG004428(NA to NA)There are an insufficient number of participants with events.
OG004
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
OG005
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).
Units
Counts
Participants
OG00024
OG0016
OG0026
OG0038
OG0049
OG0056
Title
Denominators
Categories
Title
Measurements
OG0001
OG0011
OG0021
OG0032
OG0041
OG0051
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
OG002
OG003
OG004
OG005
Other
Since an MTD was never reached for any of the rociletinib FB or HBr formulations/doses, a 750 mg BID HBr starting dose was selected based on early efficacy data from Phase 1, and enrollment into Phase 2 was initiated at this dosage. As the Phase 1 efficacy data matured, the recommended dose was adjusted to 625 mg BID based on antitumor activity and safety evaluations.
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID)
OG004
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID)
OG005
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID)
Units
Counts
Participants
OG00021
OG0019
OG002187
OG003175
OG00479
OG0054
Title
Denominators
Categories
Title
Measurements
OG00016.3(6.3 to 17.9)
OG00123.7(1.4 to NA)There are an insufficient number of participants with events.
OG00218.5(13.0 to NA)There are an insufficient number of participants with events.
OG00315.0(12.5 to 17.3)
OG00412.9(9.9 to 17.7)
OG0057.2(2.2 to NA)There are an insufficient number of participants with events.
Rociletinib free base (FB) dose 900 mg twice a day (BID)
OG002
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID)
OG003
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID)
OG004
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID)
OG005
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID)
Units
Counts
Participants
OG00021
OG0019
OG002187
OG003175
OG00480
OG0054
Title
Denominators
Categories
Title
Measurements
OG0002.6(1.3 to 4.0)
OG00110.4(1.4 to 12.2)
OG0025.7(4.2 to 6.2)
OG0035.2(4.1 to 6.2)
OG0044.3(2.9 to 6.1)
OG0057.2(2.2 to 16.7)
OG004
Rociletinib 600 mg QD FB Capsules
Rociletinib free base (FB) dose 600 mg once a day (QD).
OG005
Rociletinib 900 mg QD FB Capsules
Rociletinib free base (FB) dose 900 mg once a day (QD).
OG006
Rociletinib 100 mg BID FB Capsules
Rociletinib free base (FB) dose 100 mg twice a day (BID).
OG007
Rociletinib 300 mg BID FB Capsules
Rociletinib free base (FB) dose 300 mg twice a day (BID).
OG008
Rociletinib 600 mg BID FB Capsules
Rociletinib free base (FB) dose 600 mg twice a day (BID).
OG009
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
OG010
Rociletinib 400 mg TID FB Capsules
Rociletinib free base (FB) dose 400 mg three times a day (TID).
OG011
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
OG012
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
OG013
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
OG014
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).
Units
Counts
Participants
OG0009
OG0013
OG0023
OG0033
OG0043
OG0053
OG0063
OG0073
OG0085
OG00919
OG0103
OG01118
OG01221
OG01323
OG0146
Title
Denominators
Categories
Day 1 Cmax
ParticipantsOG0009
ParticipantsOG0013
ParticipantsOG0023
ParticipantsOG0033
ParticipantsOG0043
ParticipantsOG0053
ParticipantsOG0063
ParticipantsOG0073
ParticipantsOG0085
ParticipantsOG00919
ParticipantsOG0103
ParticipantsOG01118
ParticipantsOG01221
ParticipantsOG01323
ParticipantsOG0146
Title
Measurements
OG000537± 71
OG001533± 63
OG0021290± 1019
OG003
Day 15 Cmax
ParticipantsOG0008
ParticipantsOG0013
ParticipantsOG0023
ParticipantsOG0033
OG004
Rociletinib 600 mg QD FB Capsules
Rociletinib free base (FB) dose 600 mg once a day (QD).
OG005
Rociletinib 900 mg QD FB Capsules
Rociletinib free base (FB) dose 900 mg once a day (QD).
OG006
Rociletinib 100 mg BID FB Capsules
Rociletinib free base (FB) dose 100 mg twice a day (BID).
OG007
Rociletinib 300 mg BID FB Capsules
Rociletinib free base (FB) dose 300 mg twice a day (BID).
OG008
Rociletinib 600 mg BID FB Capsules
Rociletinib free base (FB) dose 600 mg twice a day (BID).
OG009
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
OG010
Rociletinib 400 mg TID FB Capsules
Rociletinib free base (FB) dose 400 mg three times a day (TID).
OG011
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
OG012
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
OG013
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
OG014
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).
Units
Counts
Participants
OG0009
OG0013
OG0023
OG0033
OG0043
OG0053
OG0063
OG0073
OG0085
OG00919
OG0103
OG01118
OG01221
OG01323
OG0146
Title
Denominators
Categories
Day 1 Tmax
ParticipantsOG0009
ParticipantsOG0013
ParticipantsOG0023
ParticipantsOG0033
ParticipantsOG0043
ParticipantsOG0053
ParticipantsOG0063
ParticipantsOG0073
ParticipantsOG0085
ParticipantsOG00919
ParticipantsOG0103
ParticipantsOG01118
ParticipantsOG01221
ParticipantsOG01323
ParticipantsOG0146
Title
Measurements
OG0001.5(1 to 2.5)
OG0012.5(1 to 2.5)
OG0022.5(1.5 to 6)
OG003
Day 15 Tmax
ParticipantsOG0008
ParticipantsOG0013
ParticipantsOG0023
ParticipantsOG0033
OG004
Rociletinib 600 mg QD FB Capsules
Rociletinib free base (FB) dose 600 mg once a day (QD).
OG005
Rociletinib 900 mg QD FB Capsules
Rociletinib free base (FB) dose 900 mg once a day (QD).
OG006
Rociletinib 100 mg BID FB Capsules
Rociletinib free base (FB) dose 100 mg twice a day (BID).
OG007
Rociletinib 300 mg BID FB Capsules
Rociletinib free base (FB) dose 300 mg twice a day (BID).
OG008
Rociletinib 600 mg BID FB Capsules
Rociletinib free base (FB) dose 600 mg twice a day (BID).
OG009
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
OG010
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
OG011
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
OG012
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
OG013
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).
Units
Counts
Participants
OG0009
OG0013
OG0023
OG0033
OG0043
OG0053
OG0063
OG0073
OG0085
OG00919
OG01018
OG01121
OG01223
OG0136
Title
Denominators
Categories
Day 1 AUC 0-24
ParticipantsOG0009
ParticipantsOG0012
ParticipantsOG0023
ParticipantsOG0033
ParticipantsOG0043
ParticipantsOG0053
ParticipantsOG0063
ParticipantsOG0073
ParticipantsOG0085
ParticipantsOG00918
ParticipantsOG01016
ParticipantsOG01120
ParticipantsOG01219
ParticipantsOG0136
Title
Measurements
OG0002900± 290
OG0015330± 5880
OG0028370± 6612
OG003
Day 15 AUC 0-24
ParticipantsOG0008
ParticipantsOG0012
ParticipantsOG0023
ParticipantsOG0033
OG004
Rociletinib 600 mg QD FB Capsules
Rociletinib free base (FB) dose 600 mg once a day (QD).
OG005
Rociletinib 900 mg QD FB Capsules
Rociletinib free base (FB) dose 900 mg once a day (QD).
OG006
Rociletinib 100 mg BID FB Capsules
Rociletinib free base (FB) dose 100 mg twice a day (BID).
OG007
Rociletinib 300 mg BID FB Capsules
Rociletinib free base (FB) dose 300 mg twice a day (BID).
OG008
Rociletinib 600 mg BID FB Capsules
Rociletinib free base (FB) dose 600 mg twice a day (BID).
OG009
Rociletinib 900 mg BID FB Capsules
Rociletinib free base (FB) dose 900 mg twice a day (BID).
OG010
Rociletinib 500 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).
OG011
Rociletinib 625 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
OG012
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
OG013
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).
Units
Counts
Participants
OG0009
OG0013
OG0023
OG0033
OG0043
OG0053
OG0063
OG0073
OG0085
OG00919
OG01018
OG01121
OG01223
OG0136
Title
Denominators
Categories
Day 1 T 1/2
ParticipantsOG0009
ParticipantsOG0012
ParticipantsOG0023
ParticipantsOG0033
ParticipantsOG0043
ParticipantsOG0053
ParticipantsOG0063
ParticipantsOG0072
ParticipantsOG0084
ParticipantsOG00912
ParticipantsOG01015
ParticipantsOG01114
ParticipantsOG01218
ParticipantsOG0136
Title
Measurements
OG0004.8± 3.6
OG0013.9± 2.3
OG0024.6± 1.7
OG003
Day 15 T 1/2
ParticipantsOG0008
ParticipantsOG0012
ParticipantsOG0023
ParticipantsOG0033
OG000
3
OG0013
Title
Denominators
Categories
Title
Measurements
OG000727± 354
OG0011873± 2570
OG0003
OG0013
Title
Denominators
Categories
Title
Measurements
OG0001.5(1.0 to 2.5)
OG0014.8(2.5 to 8.0)
OG0003
OG0012
Title
Denominators
Categories
Title
Measurements
OG0004780± 3625
OG0014455± 2256
OG0003
OG0013
Title
Denominators
Categories
Title
Measurements
OG00021.3± 22
OG00146.5± 51
OG0003
OG0011
Title
Denominators
Categories
Title
Measurements
OG0004.3± 1
OG0013.1± NAData for one patient only so standard deviation not applicable.
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
OG004
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
OG005
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).
Units
Counts
Participants
OG00038
OG00119
OG002209
OG003245
OG00495
OG0056
Title
Denominators
Categories
Title
Measurements
QTcF Post-Baseline <450 msec
OG00034
OG00110
OG00293
OG00399
OG00435
OG0052
QTcF Post-Baseline 450-480 msec
OG0004
OG0017
OG00271
OG00393
OG004
QTcF Post-Baseline 481-500 msec
OG0000
OG0011
OG00223
OG00324
OG004
QTcF Post-Baseline >=501 msec
OG0000
OG0011
OG00222
OG00329
OG004
Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).
OG004
Rociletinib 750 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).
OG005
Rociletinib 1000 mg BID HBr Tablets
Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).