Trial Outcomes & Findings for A Study of Safety, Tolerability and Pharmacokinetics of Nivolumab in Chinese Subjects With Previously Treated Advanced or Recurrent Solid Tumors (NCT NCT02593786)
NCT ID: NCT02593786
Last Updated: 2022-10-24
Results Overview
A drug related adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug that has a causal relationship with the treatment. AEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe and Grade 4= Life-threatening.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
58 participants
Primary outcome timeframe
From first dose to 100 days after last dose (up to approximately 28 months)
Results posted on
2022-10-24
Participant Flow
Participant milestones
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
15
|
20
|
11
|
12
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
15
|
20
|
11
|
12
|
Reasons for withdrawal
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Overall Study
Disease progression
|
12
|
16
|
10
|
7
|
|
Overall Study
Study drug toxicity
|
1
|
0
|
0
|
0
|
|
Overall Study
Adverse event unrelated to study drug
|
1
|
1
|
1
|
0
|
|
Overall Study
Participant request to discontinue study therapy
|
0
|
2
|
0
|
0
|
|
Overall Study
Other reasons
|
1
|
1
|
0
|
5
|
Baseline Characteristics
A Study of Safety, Tolerability and Pharmacokinetics of Nivolumab in Chinese Subjects With Previously Treated Advanced or Recurrent Solid Tumors
Baseline characteristics by cohort
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
> 65
|
15 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
54 Participants
n=31 Participants
|
|
Age, Customized
>= 65
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=31 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
20 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
38 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
15 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
58 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: From first dose to 100 days after last dose (up to approximately 28 months)Population: All treated participants
A drug related adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug that has a causal relationship with the treatment. AEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe and Grade 4= Life-threatening.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
The Number of Participants Experiencing Drug-Related Grade 3-4 Adverse Events (AEs)
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: From first dose to 100 days after last dose (up to approximately 28 months)Population: All treated participants
A drug related serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event that has a casual relationship with the treatment. SAEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe and Grade 4= Life-threatening.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
The Number of Participants Experiencing Drug-Related Grade 3-4 Serious Adverse Events (SAEs)
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: From first dose to 100 days after last dose (up to approximately 28 months)Population: All treated participants with least one on-treatment measurement of the corresponding laboratory parameter
The number of participants with the following laboratory abnormalities from the following on-treatment evaluations: * ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN * Total bilirubin \> 2 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=13 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=10 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results
ALT OR AST > 3XULN
|
0 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
|
The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results
ALT OR AST> 5XULN
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results
ALT OR AST> 10XULN
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results
ALT OR AST > 20XULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results
TOTAL BILIRUBIN > 2XULN
|
0 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: From first dose to 100 days after last dose (up to approximately 28 months)Population: All treated participants with least one on-treatment measurement of the corresponding laboratory parameter
The number of participants with Grade 3-4 laboratory results according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. Note: Grade 4 Toxicities not included in the below table if there were no participants that experienced Grade 4 in that category. Grade 3: prolonged recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae \[e.g., renal impairment, pulmonary infiltrates\]. Grade 4: Life-threatening; pressor or ventilatory support indicated.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
HEMOGLOBIN (Grade 3)
|
1 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
PLATELET COUNT (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
PLATELET COUNT (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
LEUKOCYTES (Grade 3)
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
LYMPHOCYTES (ABSOLUTE) (Grade 3)
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
ABSOLUTE NEUTROPHIL COUNT (Grade 3)
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
ALKALINE PHOSPHATASE (Grade 3)
|
2 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
ASPARTATE AMINOTRANSFERASE (Grade 3)
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
ALANINE AMINOTRANSFERASE (Grade 3)
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
BILIRUBIN, TOTAL (Grade 3)
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
BILIRUBIN, TOTAL (Grade 4)
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From first dose up to approximately 28 monthsPopulation: All treated participants
Best overall response (BOR) was assessed by the investigator using Response Evaluation Criteria in Solid Tumor (RECIST v1.1). Complete Response (CR) is defined as a disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Best Overall Response (BOR)
Complete Response
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Best Overall Response (BOR)
Partial Response
|
3 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
|
Best Overall Response (BOR)
Stable Disease
|
2 Participants
|
12 Participants
|
6 Participants
|
6 Participants
|
|
Best Overall Response (BOR)
Progressive Disease
|
9 Participants
|
5 Participants
|
4 Participants
|
4 Participants
|
|
Best Overall Response (BOR)
Unable to Determine
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From the date of first response (CR or PR) to the date of the first documented tumor progression or death due to any cause, whichever occurs first. (Up to approximately 28 months)Population: All treated participants with a BOR of CR or PR
Duration of response is defined as the time from the date of first response (CR or PR) to the date of the first documented tumor progression as determined using RECIST 1.1 or death due to any cause, whichever occurs first. Participants who remain alive and have not progressed will be censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy. Complete response (CR) is defined as a disappearance of all target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Other tumor types include: gastric, melanoma, neuroblastoma, colorectal cancer, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=3 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=2 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=1 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=2 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Duration of Response (DOR)
Nasopharyngeal carcinoma
|
NA Weeks
Interval 48.7 to 75.7
Insufficient number of participants with events
|
NA Weeks
Interval 34.1 to 81.1
Insufficient number of participants with events
|
—
|
NA Weeks
Interval 83.3 to 83.3
Insufficient number of participants with events
|
|
Duration of Response (DOR)
Hepatocellular carcinoma
|
—
|
—
|
—
|
NA Weeks
Interval 95.3 to 95.3
Insufficient number of participants with events
|
|
Duration of Response (DOR)
Non-small cell lung carcinoma (NSCLC)
|
NA Weeks
Interval 8.3 to 8.3
Insufficient number of participants with events
|
—
|
6.1 Weeks
Interval 6.1 to 6.1
|
—
|
SECONDARY outcome
Timeframe: From first dose up to approximately 28 monthsPopulation: All treated participants
Objective response rate (ORR) is defined as the percentage of all treated participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR) by investigator using Response Evaluation Criteria in Solid Tumor (RECIST v1.1). Complete response (CR) is defined as a disappearance of all target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Other tumor types include: gastric, melanoma, neuroblastoma, colorectal cancer, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Objective Response Rate (ORR)
Non-small cell lung carcinoma (NSCLC)
|
11.1 Percent of participants
Insufficient number of participants with events
|
0 Percent of participants
Insufficient number of participants with events
|
100 Percent of participants
Insufficient number of participants with events
|
0 Percent of participants
Insufficient number of participants with events
|
|
Objective Response Rate (ORR)
Hepatocellular carcinoma
|
—
|
0 Percent of participants
Insufficient number of participants with events
|
—
|
100 Percent of participants
Insufficient number of participants with events
|
|
Objective Response Rate (ORR)
Nasopharyngeal carcinoma
|
33.3 Percent of participants
Insufficient number of participants with events
|
11.8 Percent of participants
Interval 1.5 to 36.4
|
0 Percent of participants
Interval 0.0 to 30.8
|
100 Percent of participants
Insufficient number of participants with events
|
|
Objective Response Rate (ORR)
Other tumor types
|
—
|
—
|
—
|
0 Percent of participants
Insufficient number of participants with events
|
SECONDARY outcome
Timeframe: Week 24Population: All treated participants
Response rate at 24 weeks is defined as the percentage of all treated participants who have CR or PR by 24 weeks. Complete response (CR) is defined as a disappearance of all target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Other tumor types include: gastric, melanoma, neuroblastoma, colorectal cancer, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Response Rate at 24 Weeks
Hepatocellular carcinoma
|
—
|
0 Percent of participants
Insufficient number of participants with events
|
—
|
100 Percent of participants
Insufficient number of participants with events
|
|
Response Rate at 24 Weeks
Non-small cell lung carcinoma (NSCLC)
|
11.1 Percent of participants
Insufficient number of participants with events
|
0 Percent of participants
Insufficient number of participants with events
|
100 Percent of participants
Insufficient number of participants with events
|
0 Percent of participants
Insufficient number of participants with events
|
|
Response Rate at 24 Weeks
Nasopharyngeal carcinoma
|
33.3 Percent of participants
Insufficient number of participants with events
|
5.9 Percent of participants
Interval 0.1 to 28.7
|
0 Percent of participants
Interval 0.0 to 30.8
|
100 Percent of participants
Insufficient number of participants with events
|
|
Response Rate at 24 Weeks
Other tumor types
|
—
|
—
|
—
|
0 Percent of participants
Insufficient number of participants with events
|
SECONDARY outcome
Timeframe: Week 24Population: All treated participants
Disease control rate (DCR) at 24 weeks is defined as the percentage of all treated participants who have CR, PR or SD by 24 weeks. Complete Response (CR) is defined as a disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Other tumor types include: gastric, melanoma, neuroblastoma, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Disease Control Rate (DCR) at 24 Weeks
Colorectal Cancer
|
—
|
—
|
—
|
100 Percent of participants
Insufficient number of participants with events
|
|
Disease Control Rate (DCR) at 24 Weeks
Hepatocellular carcinoma
|
—
|
0 Percent of participants
Insufficient number of participants with events
|
—
|
100 Percent of participants
Insufficient number of participants with events
|
|
Disease Control Rate (DCR) at 24 Weeks
Non-small cell lung carcinoma (NSCLC)
|
11.1 Percent of participants
Insufficient number of participants with events
|
0 Percent of participants
Insufficient number of participants with events
|
100 Percent of participants
Insufficient number of participants with events
|
66.7 Percent of participants
Insufficient number of participants with events
|
|
Disease Control Rate (DCR) at 24 Weeks
Nasopharyngeal carcinoma
|
33.3 Percent of participants
Insufficient number of participants with events
|
23.5 Percent of participants
Interval 6.8 to 49.9
|
20.0 Percent of participants
Interval 2.5 to 55.6
|
100 Percent of participants
Insufficient number of participants with events
|
|
Disease Control Rate (DCR) at 24 Weeks
Other tumor types
|
—
|
—
|
—
|
0 Percent of participants
Insufficient number of participants with events
|
SECONDARY outcome
Timeframe: From pre-dose on day 1 Cycle 1 up to participants end of study (up to approximately 28 months)Population: All Nivolumab Treated Participants with Baseline and at Least One Post-baseline Assessment
The number of participants with the following anti-drug responses: 1. Baseline ADA positive: all participants with baseline ADA positive samples. 2. ADA Positive: participants that have at least one ADA positive sample relative to baseline at any time after initiation of treatment. 3. ADA negative: participants that have no ADA positive samples after the initiation of treatment.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=13 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=19 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=10 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment
ADA positive sample at baseline
|
1 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
|
The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment
ADA positive sample after initiation of treatment
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment
ADA Negative sample after initiation of treatment
|
12 Participants
|
19 Participants
|
10 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Cmax is the maximum observed serum concentration over time.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Cmax - Maximum Observed Serum Concentration
Cycle 1 Day 1
|
57.025 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 18
|
77.674 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 18
|
108.455 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 21
|
206.630 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 22
|
|
Cmax - Maximum Observed Serum Concentration
Cycle 3 Day 1
|
132.222 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
171.604 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 14
|
—
|
—
|
|
Cmax - Maximum Observed Serum Concentration
Cycle 5 Day 1
|
—
|
—
|
—
|
265.550 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
|
Cmax - Maximum Observed Serum Concentration
Cycle 6 Day 1
|
—
|
—
|
165.369 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 24
|
—
|
SECONDARY outcome
Timeframe: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Tmax is the time of maximum observed serum concentration.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Tmax - Time of Maximum Observed Serum Concentration
Cycle 1 Day 1
|
4.00 h
Interval 0.5 to 4.0
|
4.00 h
Interval 0.5 to 8.0
|
4.0 h
Interval 4.0 to 8.0
|
4.01 h
Interval 0.5 to 8.0
|
|
Tmax - Time of Maximum Observed Serum Concentration
Cycle 3 Day 1
|
8.00 h
Interval 4.0 to 48.2
|
8.00 h
Interval 4.0 to 48.0
|
—
|
—
|
|
Tmax - Time of Maximum Observed Serum Concentration
Cycle 5 Day 1
|
—
|
—
|
—
|
2.26 h
Interval 0.5 to 8.0
|
|
Tmax - Time of Maximum Observed Serum Concentration
Cycle 6 Day 1
|
—
|
—
|
8.00 h
Interval 0.5 to 24.1
|
—
|
SECONDARY outcome
Timeframe: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AUC (0-T) is the area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
AUC (0-T)-Area Under the Plasma Concentration-Time Curve
Cycle 5 Day 1
|
—
|
—
|
—
|
91967.438 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 35
|
|
AUC (0-T)-Area Under the Plasma Concentration-Time Curve
Cycle 1 Day 1
|
8353.429 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 29
|
11646.854 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 27
|
23567.315 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
49115.208 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
|
AUC (0-T)-Area Under the Plasma Concentration-Time Curve
Cycle 3 Day 1
|
28442.153 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 28
|
35649.049 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 28
|
—
|
—
|
|
AUC (0-T)-Area Under the Plasma Concentration-Time Curve
Cycle 6 Day 1
|
—
|
—
|
51087.588 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 44
|
—
|
SECONDARY outcome
Timeframe: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AUC (TAU) is the area under the plasma concentration-time curve in one dosing interval.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=10 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval
Cycle 1 Day 1
|
8732.232 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 24
|
12112.137 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 24
|
23567.315 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
49115.208 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
|
AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval
Cycle 3 Day 1
|
30823.993 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 21
|
37794.083 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 22
|
—
|
—
|
|
AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval
Cycle 5 Day 1
|
—
|
—
|
—
|
100655.626 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 28
|
|
AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval
Cycle 6 Day 1
|
—
|
—
|
53162.102 h*ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 40
|
—
|
SECONDARY outcome
Timeframe: End of infusion on Day 1 of Cycle 1, 3, 5, 6Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Ceoinf is the serum concentration achieved at the end of study drug infusion.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=18 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion
Cycle 6 Day 1
|
—
|
—
|
155.811 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 24
|
—
|
|
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion
Cycle 1 Day 1
|
55.020 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
66.746 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 22
|
93.168 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 23
|
171.494 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 23
|
|
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion
Cycle 3 Day 1
|
122.051 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
152.058 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 20
|
—
|
—
|
|
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion
Cycle 5 Day 1
|
—
|
—
|
—
|
254.704 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 18
|
SECONDARY outcome
Timeframe: Day 1 Cycle 3, 5, 6 (168 hours post dose [Cohort A-B], 336 hours post dose [Cohort C-D])Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Ctrough is the trough observed serum concentration at the end of dosing interval.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=7 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=9 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=7 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=6 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Ctrough - Trough Observed Serum Concentration at the End of Dosing Interval
Cycle 3 Day 1
|
62.417 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 26
|
62.115 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 39
|
—
|
—
|
|
Ctrough - Trough Observed Serum Concentration at the End of Dosing Interval
Cycle 5 Day 1
|
—
|
—
|
—
|
92.796 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 39
|
|
Ctrough - Trough Observed Serum Concentration at the End of Dosing Interval
Cycle 6 Day 1
|
—
|
—
|
61.530 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 35
|
—
|
SECONDARY outcome
Timeframe: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Ctau is the concentration at the end of dosing interval.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=13 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=18 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=10 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Ctau - Concentration at the End of Dosing Interval
Cycle 6 Day 1
|
—
|
—
|
65.762 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 35
|
—
|
|
Ctau - Concentration at the End of Dosing Interval
Cycle 1 Day 1
|
16.430 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 26
|
20.788 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 30
|
26.143 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
40.910 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 25
|
|
Ctau - Concentration at the End of Dosing Interval
Cycle 3 Day 1
|
65.286 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 27
|
78.278 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 31
|
—
|
—
|
|
Ctau - Concentration at the End of Dosing Interval
Cycle 5 Day 1
|
—
|
—
|
—
|
90.201 ug/mL
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 39
|
SECONDARY outcome
Timeframe: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. T-HALFeff is the effective elimination half-life that explains the degree of observed AUC accumulation calculated based on ratio of an exposure measure at steady state to that after the first dose (exposure measure includes AUC(TAU), Cmax and Ctau).
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=7 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=9 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=7 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=6 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
T-HALFeff - Effective Elimination Half-Life
Cycle 3 Day 1
|
551.194 h
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 24
|
510.262 h
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 22
|
—
|
—
|
|
T-HALFeff - Effective Elimination Half-Life
Cycle 5 Day 1
|
—
|
—
|
—
|
732.44 h
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 36
|
|
T-HALFeff - Effective Elimination Half-Life
Cycle 6 Day 1
|
—
|
—
|
677.642 h
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 56
|
—
|
SECONDARY outcome
Timeframe: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. CLT is the total body clearance.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=7 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=9 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=7 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=6 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
CLT - Total Body Clearance
Cycle 3 Day 1
|
5.732 mL/hr
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 26
|
6.350 mL/hr
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 22
|
—
|
—
|
|
CLT - Total Body Clearance
Cycle 5 Day 1
|
—
|
—
|
—
|
4.769 mL/hr
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 39
|
|
CLT - Total Body Clearance
Cycle 6 Day 1
|
—
|
—
|
6.772 mL/hr
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 35
|
—
|
SECONDARY outcome
Timeframe: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AI of Cmax refers to the accumulation index calculated based on ratio of an exposure measure of Cmax at steady state to that after the first dose.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=7 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=9 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=7 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=6 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
AI - Accumulation Index (Cmax)
Cycle 3 Day 1
|
2.150 (ug/mL)/(ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 12
|
2.034 (ug/mL)/(ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 15
|
—
|
—
|
|
AI - Accumulation Index (Cmax)
Cycle 5 Day 1
|
—
|
—
|
—
|
1.255 (ug/mL)/(ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 29
|
|
AI - Accumulation Index (Cmax)
Cycle 6 Day 1
|
—
|
—
|
1.613 (ug/mL)/(ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 17
|
—
|
SECONDARY outcome
Timeframe: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AI of Ctau refers to the accumulation index calculated based on ratio of an exposure measure of Ctau at steady state to that after the first dose.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=6 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=8 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=6 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=5 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
AI - Accumulation Index (Ctau)
Cycle 3 Day 1
|
3.333 (ug/mL)/(ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 25
|
3.215 (ug/mL)/(ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 23
|
—
|
—
|
|
AI - Accumulation Index (Ctau)
Cycle 5 Day 1
|
—
|
—
|
—
|
2.053 (ug/mL)/(ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 22
|
|
AI - Accumulation Index (Ctau)
Cycle 6 Day 1
|
—
|
—
|
2.675 (ug/mL)/(ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 24
|
—
|
SECONDARY outcome
Timeframe: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)Population: All treated participants with evaluable serum concentration data
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AI of AUC refers to the accumulation index calculated based on ratio of an exposure measure of AUC at steady state to that after the first dose.
Outcome measures
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=7 Participants
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=9 Participants
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=7 Participants
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=6 Participants
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
AI - Accumulation Index (AUC)
Cycle 3 Day 1
|
2.942 (hr*ug/mL)/(hr*ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 18
|
2.707 (hr*ug/mL)/(hr*ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 15
|
—
|
—
|
|
AI - Accumulation Index (AUC)
Cycle 5 Day 1
|
—
|
—
|
—
|
2.033 (hr*ug/mL)/(hr*ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 24
|
|
AI - Accumulation Index (AUC)
Cycle 6 Day 1
|
—
|
—
|
2.389 (hr*ug/mL)/(hr*ug/mL)
Geometric Coefficient of Variation NA
Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
%CV = 31
|
—
|
Adverse Events
Cohort A: Nivolumab 3 mg/kg Q2W
Serious events: 6 serious events
Other events: 14 other events
Deaths: 4 deaths
Cohort B: Nivolumab 240 mg Q2W
Serious events: 8 serious events
Other events: 20 other events
Deaths: 7 deaths
Cohort C: Nivolumab 360 mg Q3W
Serious events: 2 serious events
Other events: 11 other events
Deaths: 0 deaths
Cohort D: Nivolumab 480 mg Q4W
Serious events: 7 serious events
Other events: 12 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 participants at risk
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 participants at risk
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 participants at risk
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 participants at risk
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Cardiac disorders
Pericardial effusion
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Endocrine disorders
Hypothalamo-pituitary disorder
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Eye disorders
Optic neuropathy
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Pancreatitis
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Asthenia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Appendicitis
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Septic shock
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Injury, poisoning and procedural complications
Tracheal haemorrhage
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Platelet count decreased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
20.0%
4/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Nervous system disorders
Brain oedema
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Nervous system disorders
Cerebellar haemorrhage
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Nervous system disorders
Paraplegia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Asphyxia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
Other adverse events
| Measure |
Cohort A: Nivolumab 3 mg/kg Q2W
n=15 participants at risk
Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort B: Nivolumab 240 mg Q2W
n=20 participants at risk
Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43.
|
Cohort C: Nivolumab 360 mg Q3W
n=11 participants at risk
Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle.
|
Cohort D: Nivolumab 480 mg Q4W
n=12 participants at risk
Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle
|
|---|---|---|---|---|
|
Metabolism and nutrition disorders
Hypochloraemia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
15.0%
3/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
16.7%
2/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
20.0%
4/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
27.3%
3/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
33.3%
4/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Blood and lymphatic system disorders
Granulocytosis
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
27.3%
3/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
15.0%
3/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
27.3%
3/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Blood and lymphatic system disorders
Leukopenia
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
18.2%
2/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
15.0%
3/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Cardiac disorders
Cardiac discomfort
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Ear and labyrinth disorders
Ear discomfort
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Ear and labyrinth disorders
Tinnitus
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Endocrine disorders
Hyperthyroidism
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Endocrine disorders
Hypothyroidism
|
13.3%
2/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
30.0%
6/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
54.5%
6/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Eye disorders
Vision blurred
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Eye disorders
Visual impairment
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Eye disorders
Vitreous floaters
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
13.3%
2/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Abnormal faeces
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Constipation
|
13.3%
2/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
27.3%
3/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
16.7%
2/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
15.0%
3/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Epigastric discomfort
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Nausea
|
13.3%
2/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Gastrointestinal disorders
Vomiting
|
26.7%
4/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
27.3%
3/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Asthenia
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
25.0%
3/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Chest discomfort
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
18.2%
2/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Chest pain
|
13.3%
2/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Chills
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Fatigue
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
15.0%
3/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Influenza like illness
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Malaise
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
30.0%
6/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Oedema peripheral
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Pain
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
General disorders
Pyrexia
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
20.0%
4/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
36.4%
4/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
16.7%
2/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Bronchitis
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Dacryocystitis
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Otitis media
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Pneumonia
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
20.0%
4/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
25.0%
3/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
30.0%
6/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Injury, poisoning and procedural complications
Skin injury
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
30.0%
6/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
16.7%
2/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Aspartate aminotransferase increased
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
30.0%
6/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
16.7%
2/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Blood albumin decreased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
15.0%
3/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Blood creatinine increased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
16.7%
2/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Blood thyroid stimulating hormone increased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
C-reactive protein increased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
36.4%
4/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Granulocyte count increased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Haemoglobin decreased
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
15.0%
3/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
18.2%
2/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Platelet count decreased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Platelet count increased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Protein urine present
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
18.2%
2/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Urinary occult blood
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
Weight decreased
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Investigations
White blood cell count decreased
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
16.7%
2/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
33.3%
5/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
13.3%
2/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
18.2%
2/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
25.0%
5/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
16.7%
2/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
13.3%
2/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Nervous system disorders
Brain oedema
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Nervous system disorders
Dizziness
|
26.7%
4/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
25.0%
5/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
16.7%
2/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Nervous system disorders
Headache
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Psychiatric disorders
Insomnia
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Psychiatric disorders
Poor quality sleep
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Renal and urinary disorders
Micturition disorder
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
25.0%
5/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
27.3%
3/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial haemorrhage
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
10.0%
2/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
27.3%
3/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
18.2%
2/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal discomfort
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
27.3%
3/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Leukoderma
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Papule
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
18.2%
2/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
5/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
15.0%
3/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
36.4%
4/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Telangiectasia
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Vascular disorders
Hot flush
|
6.7%
1/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Vascular disorders
Hypertension
|
13.3%
2/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
25.0%
3/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Vascular disorders
Hypotension
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
9.1%
1/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Vascular disorders
Phlebitis
|
20.0%
3/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
5.0%
1/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
|
Vascular disorders
Venous thrombosis limb
|
0.00%
0/15 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/20 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
0.00%
0/11 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
8.3%
1/12 • All-cause mortality was assessed from participants first dose to their study completion (up to approximately 28 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to an approximately 14 months, maximum of 28 months)
|
Additional Information
Bristol-Myers Squibb Study Director
Bristol-Myers Squibb
Phone: Please email
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER