Trial Outcomes & Findings for Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025) (NCT NCT01668784)
NCT ID: NCT01668784
Last Updated: 2022-08-09
Results Overview
Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Interim analysis for the Primary Endpoint occurred after 398 deaths (70% of the total OS events needed for final analysis). At that time the data monitoring committee noted that the pre-specified boundary for OS (nominal significance level p \< 0.0148) was crossed while no new safety signals that would affect continuation of the study were found. The study was stopped early by the Sponsor, Bristol-Myers Squibb (BMS) and the interim analysis became the final analysis. As a result, participants in the everolimus groups could be assessed for a crossover to nivolumab treatment if they met all inclusion criteria.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
821 participants
Primary outcome timeframe
Randomization until 398 deaths, up to May 2015 (approximately 30 months)
Results posted on
2022-08-09
Participant Flow
803 Participants Treated
Participant milestones
| Measure |
Nivolumab
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Randomized (Pre-treatment)
STARTED
|
410
|
411
|
|
Randomized (Pre-treatment)
COMPLETED
|
406
|
397
|
|
Randomized (Pre-treatment)
NOT COMPLETED
|
4
|
14
|
|
Treatment Period
STARTED
|
406
|
397
|
|
Treatment Period
COMPLETED
|
0
|
0
|
|
Treatment Period
NOT COMPLETED
|
406
|
397
|
Reasons for withdrawal
| Measure |
Nivolumab
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Randomized (Pre-treatment)
Disease Progression
|
0
|
1
|
|
Randomized (Pre-treatment)
Request to Discontinue Study Treatment
|
0
|
3
|
|
Randomized (Pre-treatment)
Withdrawal by Subject
|
1
|
8
|
|
Randomized (Pre-treatment)
Poor/Non-Compliance
|
1
|
0
|
|
Randomized (Pre-treatment)
No Longer Meets Study Criteria
|
2
|
1
|
|
Randomized (Pre-treatment)
participant requested to be treated a local facility
|
0
|
1
|
|
Treatment Period
Disease Progression
|
316
|
293
|
|
Treatment Period
Study Drug Toxicity
|
46
|
53
|
|
Treatment Period
Death
|
1
|
1
|
|
Treatment Period
Adverse Event Unrelated to Study Drug
|
14
|
14
|
|
Treatment Period
Request to Discontinue Study Treatment
|
14
|
21
|
|
Treatment Period
Withdrawal by Subject
|
5
|
3
|
|
Treatment Period
Maximal Clinical Benefit
|
3
|
3
|
|
Treatment Period
Other
|
2
|
8
|
|
Treatment Period
Administrative Reason by Sponsor
|
5
|
1
|
Baseline Characteristics
Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)
Baseline characteristics by cohort
| Measure |
Nivolumab
n=410 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=411 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Total
n=821 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.6 years
STANDARD_DEVIATION 10.87 • n=5 Participants
|
61.9 years
STANDARD_DEVIATION 10.43 • n=7 Participants
|
61.3 years
STANDARD_DEVIATION 10.66 • n=5 Participants
|
|
Sex: Female, Male
Female
|
95 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
202 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
315 Participants
n=5 Participants
|
304 Participants
n=7 Participants
|
619 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
42 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
353 Participants
n=5 Participants
|
367 Participants
n=7 Participants
|
720 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
13 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization until 398 deaths, up to May 2015 (approximately 30 months)Population: All randomized participants; any participants that was randomized to any treatment group in the study.
Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Interim analysis for the Primary Endpoint occurred after 398 deaths (70% of the total OS events needed for final analysis). At that time the data monitoring committee noted that the pre-specified boundary for OS (nominal significance level p \< 0.0148) was crossed while no new safety signals that would affect continuation of the study were found. The study was stopped early by the Sponsor, Bristol-Myers Squibb (BMS) and the interim analysis became the final analysis. As a result, participants in the everolimus groups could be assessed for a crossover to nivolumab treatment if they met all inclusion criteria.
Outcome measures
| Measure |
Nivolumab
n=410 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=411 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Overall Survival (OS) at Primary Endpoint
|
25.00 months
Interval 21.75 to
N.A.: Not Available: Too few events to estimate the upper limit of the confidence interval
|
19.55 months
Interval 17.64 to 23.06
|
SECONDARY outcome
Timeframe: from randomization up to disease progression or death (approximately up to 105 Months)Population: All randomized participants; any participants that was randomized to any treatment group in the study.
ORR is defined as Percentage of participants with a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference. Tumor assessments began at 8 weeks following randomization and continued every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or death. CIs used Clopper and Pearson.
Outcome measures
| Measure |
Nivolumab
n=410 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=411 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Investigator-assessed Objective Response Rate (ORR)
|
25.9 percentage of participants
Interval 21.7 to 30.4
|
6.1 percentage of participants
Interval 4.0 to 8.8
|
SECONDARY outcome
Timeframe: From randomization to date of disease progression or death or censoring if no progression or death occurred (approximately 105 months)Population: All randomized participants with a response; any participants that were randomized to any treatment group in the study and that had a response.
Duration of objective response is defined as the time from study start date to response, CR or partial response, PR) to the date of the first documented tumor progression as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. For participants who neither progress nor die, the duration of objective response were censored at the same time they were censored for the primary definition. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference. Based on Kaplan-Meier Estimates.
Outcome measures
| Measure |
Nivolumab
n=106 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=25 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Investigator-assessed Duration of Objective Response
|
13.11 months
Interval 9.26 to 19.75
|
10.18 months
Interval 5.39 to 18.73
|
SECONDARY outcome
Timeframe: Randomization to date of first response (approximately 105 months)Population: All randomized participants with a response; any participants that was randomized to any treatment group in the study and that had a response.
Time to objective response is defined as the time from randomization to first response (complete response, CR or partial response, PR). CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference.
Outcome measures
| Measure |
Nivolumab
n=106 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=25 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Investigator-assessed Time to Objective Response
|
3.55 months
Interval 1.4 to 24.8
|
3.71 months
Interval 1.5 to 68.9
|
SECONDARY outcome
Timeframe: from randomization up to disease progression or death (approximately up to 105 Months)Population: All randomized participants; any participants that was randomized to any treatment group in the study.
PFS=time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. Participants who die without a reported prior progression and without subsequent anti-cancer therapy were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the date they were randomized. Participants who received any subsequent anti-cancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to or on initiation date of the subsequent anti-cancer therapy. Progressive disease: \>=20% increase in sum of target lesion diameters and sum must show absolute increase of \>=5mm; smallest sum on study as reference. Based on Kaplan-Meier Estimates.
Outcome measures
| Measure |
Nivolumab
n=410 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=411 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Investigator-assessed Time of Progression-free Survival (PFS)
|
4.21 months
Interval 3.68 to 5.36
|
4.50 months
Interval 3.71 to 5.52
|
SECONDARY outcome
Timeframe: Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months)Population: PD-L1 quantifiable participants; All randomized participants with quantifiable PD-L1 expression at baseline
Quantifiable PD-L1 expression=percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay. If the PD-L1 staining could not be quantified it was classified as: indeterminate=tumor cell membrane staining hampered for reasons attributed to biology of tumor biopsy specimen and not due to improper sample preparation or handling; not evaluable=tumor biopsy specimen was not optimally collected or prepared. Not evaluable determined from H\&E process before the tumor biopsy specimen was sent for evaluation or from H\&E process during PD-L1 evaluation; baseline PD-L1 expression=if more than one tumor biopsy specimen was available, the most recently collected specimen with a quantifiable result. If all specimens for a given participant are either indeterminate or not evaluable, then the PD-L1 expression was considered indeterminate as long as at least one specimen is indeterminate. Otherwise, PD-L1 expression was considered not evaluable.
Outcome measures
| Measure |
Nivolumab
n=370 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=386 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level
Participant PD-L1 expression >=1%
|
5.36 months
Interval 2.04 to 7.46
|
4.17 months
Interval 3.09 to 5.52
|
|
Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level
Participant PD-L1 expression <1%
|
3.94 months
Interval 3.68 to 5.36
|
4.67 months
Interval 3.71 to 5.72
|
SECONDARY outcome
Timeframe: Day of first dose to 30 days post study completion (approximately 106 months)Population: All treated participants; all participants who received at least one dose of nivolumab or everolimus
Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Outcome measures
| Measure |
Nivolumab
n=406 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=397 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
Deaths
|
324 Participants
|
342 Participants
|
|
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
SAEs
|
211 Participants
|
177 Participants
|
|
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
Drug related SAEs
|
51 Participants
|
55 Participants
|
|
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
Discontinued due to AEs
|
85 Participants
|
82 Participants
|
|
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
Adverse Events
|
398 Participants
|
387 Participants
|
|
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
Drug related AEs
|
327 Participants
|
353 Participants
|
|
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
Discontinued due to Drug-related AEs
|
40 Participants
|
51 Participants
|
SECONDARY outcome
Timeframe: from randomization up to disease progression or death (approximately up to 105 Months)Population: All randomized participants; any participants that was randomized to any treatment group in the study.
Disease-related symptom progression rate (DRSPR)=a decrease of two points in the Functional Assessment of Cancer Therapy-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS) questionnaire relative to the participant's baseline FKSI-DRS score with no later increase above this threshold observed during the course of the study. The 9 items of the FKSI-DRS were summarized into a symptom scale ranging in score from 0 to 36, with 0 being the worst possible score and 36 being the best possible score. A single measure reporting a decrease of at least 2 units was considered disease-related symptom progression only if it was the last one available for the participant. In order to consider a questionnaire received as valid, over 50% of the items were to be completed. Calculated by the Clopper-Pearson method for each treatment group.
Outcome measures
| Measure |
Nivolumab
n=410 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=411 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Percentage of Participants With Disease-related Symptom Progression (DRSP)
Disease-related Symptom Progression Rate (DRSPR)
|
44.6 percentage of participants
Interval 39.0 to 50.3
|
54.6 percentage of participants
Interval 49.2 to 60.0
|
|
Percentage of Participants With Disease-related Symptom Progression (DRSP)
DRSPR Including Death and Investigator Progression
|
95.5 percentage of participants
Interval 92.6 to 97.5
|
99.4 percentage of participants
Interval 97.9 to 99.9
|
SECONDARY outcome
Timeframe: Day 1 to 30 days post study completion (approximately 106 months)Population: To all treated participants with evaluable measurements
Aspartate aminotransferase, AST. Alanine aminotransaminase, ALT. Total bilirubin, tBIL. Thyroid stimulating hormone, TSH. Upper limit of normal (ULN). Units per Liter (U/L). Results reported in International System of Units (SI).
Outcome measures
| Measure |
Nivolumab
n=406 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=397 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
ALT or AST > 3.0*ULN
|
32 Participants
|
15 Participants
|
|
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
ALT or AST > 5.0*ULN
|
20 Participants
|
7 Participants
|
|
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
ALT or AST > 10.0*ULN
|
9 Participants
|
1 Participants
|
|
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
ALT or AST > 20.0*ULN
|
2 Participants
|
0 Participants
|
|
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
Total Bilirubin > 2.0*ULN
|
6 Participants
|
2 Participants
|
|
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
ALT or AST>3.0*ULN, tBIL>2.0 ULN, 1day
|
3 Participants
|
0 Participants
|
|
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
ALT or AST>3.0*ULN, tBIL>2.0 ULN,30day
|
4 Participants
|
1 Participants
|
|
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
TSH > ULN
|
159 Participants
|
78 Participants
|
|
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
TSH < LLN
|
60 Participants
|
60 Participants
|
SECONDARY outcome
Timeframe: Day 1 to 30 days post study completion (approximately 106 months)Population: To all treated participants with evaluable measurements
Common Terminology Criteria (CTC) version 4.0 in International System of Units (SI); Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Hematology parameters=Hemoglobin (Gr 3: \< 8.0 g/dL), Platelet Count (Gr 3: 25.0 -\< 50.0\*10\^9 c/L; Gr 4: \< 25.0\*10\^9 c/L), Leukocyte Count (Gr 3: 1.0 -\< 2.0\*10\^3 c/µL; Gr4: \< 1.0\*10\^3 c/µL), Absolute Lymphocyte Count (Gr 3: 0.2 -\< 0.5\*10\^3 c/µL; Gr 4: \< 0.2\*10\^3 c/µL), Absolute Neutrophil Count (Gr 3: 0.5 - \< 1.0\*10\^3 c/µL; Gr 4: \< 0.5\*10\^3 c/µL). Liver Function parameters=Alkaline Phosphatase (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), AST (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), ALT (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), tBIL (Gr 3: \> 3.0 - 10.0 mg/dL \* ULN; Gr 4: \> 10.0 mg/dL \* ULN). Renal parameter=Creatinine (Grade: Gr3: \> 3.0 - 6.0 mg/dL \*ULN; Gr4: \> 6.0 mg/dL \*ULN). Cells per microliter (c/µL). Cells per Liter (c/L). Grams per deciliter (g/dL). Milligrams per deciliter (mg/dL).
Outcome measures
| Measure |
Nivolumab
n=406 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=397 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Platelet Count, Grade 3
|
1 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Leukocytes, Grade 3
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Leukocytes, Grade 4
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Lymphocytes (absolute), Grade 3
|
28 Participants
|
43 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Lymphocytes (absolute), Grade 4
|
3 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Absolute Neutrophil Count, Grade 3
|
0 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Absolute Neutrophil Count, Grade 4
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Aspartate Aminotransferase, Grade 4
|
2 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Alanine Aminotransferase, Grade 4
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Creatinine, Grade 3
|
5 Participants
|
5 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Creatinine, Grade 4
|
3 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hypercalcemia, Grade 3
|
7 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hypercalcemia, Grade 4
|
4 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hypocalcemia, Grade 4
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hypokalemia, Grade 3
|
5 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hypomagnesmia, Grade 3
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hemoglobin, Grade 3
|
33 Participants
|
61 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Platelet Count, Grade 4
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Alkaline Phosphatase, Grade 3
|
11 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Aspartate Aminotransferase, Grade 3
|
9 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Alanine Aminotransferase, Grade 3
|
12 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Bilirubin Total, Grade 3
|
3 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hypocalcemia, Grade 3
|
2 Participants
|
4 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hyperkalemia, Grade 3
|
11 Participants
|
7 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hyperkalemia, Grade 4
|
3 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hypermagnesmia, Grade 3
|
3 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hyponatremia, Grade 3
|
26 Participants
|
22 Participants
|
|
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hyponatremia, Grade 4
|
1 Participants
|
1 Participants
|
POST_HOC outcome
Timeframe: from randomization up to disease progression or death (approximately up to 105 months)Population: All Randomized Participants
Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Interim analysis for the Primary Endpoint occurred after 398 deaths (70% of the total OS events needed for final analysis). At that time the data monitoring committee noted that the pre-specified boundary for OS (nominal significance level p \< 0.0148) was crossed while no new safety signals that would affect continuation of the study were found. The study was stopped early by the Sponsor, Bristol-Myers Squibb (BMS) and the interim analysis became the final analysis. As a result, participants in the everolimus groups could be assessed for a crossover to nivolumab treatment if they met all inclusion criteria. This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date.
Outcome measures
| Measure |
Nivolumab
n=410 Participants
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
Everolimus
n=411 Participants
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Extended Collection to Post Hoc Overall Survival (OS)
|
25.82 Months
Interval 22.21 to 29.77
|
19.55 Months
Interval 17.64 to 21.88
|
Adverse Events
NIVOLUMAB
Serious events: 248 serious events
Other events: 392 other events
Deaths: 324 deaths
EVEROLIMUS
Serious events: 243 serious events
Other events: 379 other events
Deaths: 342 deaths
Serious adverse events
| Measure |
NIVOLUMAB
n=406 participants at risk
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
EVEROLIMUS
n=397 participants at risk
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
2.2%
9/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
3.8%
15/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Blood and lymphatic system disorders
Methaemoglobinaemia
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Acute coronary syndrome
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Acute myocardial infarction
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Angina pectoris
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Arrhythmia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Atrial fibrillation
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Atrial flutter
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Atrioventricular block
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Cardiac failure
|
0.99%
4/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Cardiac failure chronic
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Cardiac ventricular thrombosis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Myocardial infarction
|
1.7%
7/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Congenital, familial and genetic disorders
Pancreas divisum
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Ear and labyrinth disorders
Tympanic membrane perforation
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Endocrine disorders
Adrenal insufficiency
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Endocrine disorders
Hypercalcaemia of malignancy
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Endocrine disorders
Hypopituitarism
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Eye disorders
Corneal disorder
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Eye disorders
Retinal detachment
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Eye disorders
Visual impairment
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
1.2%
5/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.0%
4/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Ascites
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Autoimmune colitis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Colitis
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Constipation
|
1.2%
5/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Diabetic gastroparesis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
2.0%
8/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Enterocolitis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Food poisoning
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Haemoperitoneum
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Ileus
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Immune-mediated enterocolitis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Intra-abdominal haemorrhage
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Large intestinal haemorrhage
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Melaena
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Nausea
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Oesophageal obstruction
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Pancreatitis
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Pneumoperitoneum
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.5%
6/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Vomiting
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Asthenia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Chest pain
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Chills
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Disease progression
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Fatigue
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Gait disturbance
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
General physical health deterioration
|
0.99%
4/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.3%
5/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Hernia
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Hernia pain
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Hyperpyrexia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Inadequate analgesia
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Influenza like illness
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Non-cardiac chest pain
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Oedema peripheral
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Pain
|
0.99%
4/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Performance status decreased
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Peripheral swelling
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Polyp
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Pyrexia
|
1.7%
7/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.5%
6/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Systemic inflammatory response syndrome
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Biliary colic
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Biliary obstruction
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Cholecystitis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Hepatic cytolysis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Hepatic pain
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Hepatitis acute
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Hepatorenal failure
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Immune-mediated hepatitis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Immune system disorders
Anaphylactic reaction
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Abdominal infection
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Anal abscess
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Appendicitis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Brain abscess
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Bronchiolitis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Bronchitis
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Cellulitis
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Cystitis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Device related sepsis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Escherichia infection
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Febrile infection
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Gastroenteritis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Gastroenteritis viral
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Genital infection fungal
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Groin infection
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Infection
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways disease
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Influenza
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Lymphangitis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Meningitis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Periorbital cellulitis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Peritonitis bacterial
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Pneumocystis jirovecii pneumonia
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Pneumonia
|
4.7%
19/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.3%
25/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Pneumonia mycoplasmal
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Psoas abscess
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Respiratory tract infection
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Sepsis
|
2.2%
9/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Septic shock
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Skin infection
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Soft tissue infection
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Spinal cord infection
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Splenic infection
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Urinary tract infection
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.3%
5/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Urosepsis
|
0.99%
4/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Wound infection
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Fall
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Incision site impaired healing
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Post procedural swelling
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Product administration error
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Injury, poisoning and procedural complications
Wound complication
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Alanine aminotransferase increased
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Aspartate aminotransferase increased
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Blood bilirubin increased
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Blood creatinine increased
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Blood culture positive
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Blood glucose increased
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Blood potassium increased
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
General physical condition abnormal
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Haemoglobin decreased
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Lipase increased
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Pancreatic enzymes increased
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Transaminases increased
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Viral test positive
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Cachexia
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.3%
5/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Glucose tolerance impaired
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
2.5%
10/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.3%
5/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.2%
5/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.3%
5/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.0%
4/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.99%
4/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Back disorder
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.2%
9/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.8%
7/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Bone disorder
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Bone lesion
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Osteitis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Osteolysis
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis of jaw
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
1.2%
5/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.0%
4/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Soft tissue necrosis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acoustic neuroma
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.99%
4/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Duodenal neoplasm
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial tumour haemorrhage
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangiosis carcinomatosa
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
15.8%
64/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
21.4%
85/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to abdominal cavity
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to adrenals
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
1.7%
7/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to pancreas
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to peritoneum
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to spine
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to thyroid
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic renal cell carcinoma
|
0.99%
4/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal adenocarcinoma
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma recurrent
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin cancer metastatic
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Central nervous system haemorrhage
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Cerebral ischaemia
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Cerebrovascular accident
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.5%
6/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Dizziness
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Dural arteriovenous fistula
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Encephalopathy
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Facial spasm
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Hyperammonaemic encephalopathy
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Immune-mediated encephalitis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Intracranial pressure increased
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Intraventricular haemorrhage
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Memory impairment
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Nerve compression
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Nervous system disorder
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Seizure
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Somnolence
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Spinal cord compression
|
2.2%
9/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Syncope
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Thalamus haemorrhage
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Vasogenic cerebral oedema
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Product Issues
Device loosening
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Psychiatric disorders
Completed suicide
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Psychiatric disorders
Confusional state
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Psychiatric disorders
Delirium
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Psychiatric disorders
Mental disorder
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Psychiatric disorders
Mental status changes
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Acute kidney injury
|
3.0%
12/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.5%
6/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Renal failure
|
1.7%
7/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.5%
6/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Renal impairment
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Renal mass
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Renal tubular necrosis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Tubulointerstitial nephritis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.2%
9/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
2.0%
8/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.99%
4/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
1.0%
4/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Organising pneumonia
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.9%
16/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
4.8%
19/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.5%
10/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
3.3%
13/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax spontaneous
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.99%
4/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
2.0%
8/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary infarction
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary mass
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.76%
3/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.50%
2/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.49%
2/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Aortic dissection
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Hypertension
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Hypertensive crisis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Hypotension
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Orthostatic hypotension
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Thrombosis
|
0.00%
0/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.25%
1/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Venous thrombosis
|
0.25%
1/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
0.00%
0/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
Other adverse events
| Measure |
NIVOLUMAB
n=406 participants at risk
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
EVEROLIMUS
n=397 participants at risk
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
22.9%
93/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
37.5%
149/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Endocrine disorders
Hypothyroidism
|
9.6%
39/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
3.8%
15/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
11.3%
46/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
11.1%
44/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
27/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
5.5%
22/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Constipation
|
27.1%
110/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
23.4%
93/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
30.0%
122/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
35.5%
141/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Dry mouth
|
7.4%
30/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.3%
25/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Dyspepsia
|
3.7%
15/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
5.0%
20/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Nausea
|
33.3%
135/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
35.0%
139/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Stomatitis
|
7.1%
29/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
31.5%
125/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Gastrointestinal disorders
Vomiting
|
19.0%
77/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
20.2%
80/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Asthenia
|
10.8%
44/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
17.9%
71/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Chills
|
7.9%
32/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
7.6%
30/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Fatigue
|
53.0%
215/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
49.4%
196/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Malaise
|
5.4%
22/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
3.5%
14/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Mucosal inflammation
|
5.2%
21/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
22.4%
89/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Oedema peripheral
|
18.0%
73/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
27.7%
110/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Pain
|
5.2%
21/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.5%
26/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
General disorders
Pyrexia
|
20.0%
81/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
21.2%
84/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Nasopharyngitis
|
10.6%
43/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.3%
25/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Pneumonia
|
2.7%
11/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
7.3%
29/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Sinusitis
|
2.5%
10/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
5.5%
22/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
8.4%
34/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.5%
26/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Infections and infestations
Urinary tract infection
|
5.9%
24/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.3%
25/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Alanine aminotransferase increased
|
7.1%
29/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
7.6%
30/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Aspartate aminotransferase increased
|
8.4%
34/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
8.3%
33/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Blood alkaline phosphatase increased
|
7.1%
29/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
4.5%
18/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Blood cholesterol increased
|
2.0%
8/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
7.8%
31/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Blood creatinine increased
|
15.3%
62/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
15.4%
61/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Platelet count decreased
|
2.7%
11/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
5.3%
21/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Investigations
Weight decreased
|
14.3%
58/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
16.9%
67/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
26.8%
109/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
36.5%
145/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
6.7%
27/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
4.3%
17/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.74%
3/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
9.6%
38/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
9.4%
38/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
16.6%
66/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.7%
27/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
5.0%
20/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
5.9%
24/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
19.4%
77/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.7%
27/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.0%
24/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
29.6%
120/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
19.9%
79/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
24.4%
99/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
19.4%
77/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
4.7%
19/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
5.5%
22/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
5.4%
22/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
4.5%
18/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.7%
23/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
4.5%
18/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
7.9%
32/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
5.5%
22/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.9%
40/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.0%
24/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.8%
60/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
11.3%
45/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Dizziness
|
9.9%
40/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
9.3%
37/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Dysgeusia
|
2.2%
9/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
10.1%
40/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Headache
|
16.0%
65/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
16.6%
66/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Nervous system disorders
Taste disorder
|
2.2%
9/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
5.3%
21/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Psychiatric disorders
Anxiety
|
8.1%
33/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.3%
25/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Psychiatric disorders
Depression
|
6.2%
25/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
3.5%
14/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Psychiatric disorders
Insomnia
|
9.9%
40/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
9.6%
38/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Renal and urinary disorders
Pollakiuria
|
5.2%
21/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
3.8%
15/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
36.0%
146/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
38.3%
152/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
8.9%
36/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
8.1%
32/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
24.9%
101/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
28.7%
114/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
6.4%
26/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
7.1%
28/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.7%
19/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
16.6%
66/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
5.4%
22/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
4.3%
17/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.9%
24/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
3.8%
15/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.2%
21/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.8%
27/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.2%
13/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
5.5%
22/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.9%
24/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
14.1%
56/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.7%
23/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.3%
25/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
3.4%
14/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.0%
24/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
12.3%
50/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
12.6%
50/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
5.4%
22/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
9.6%
38/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
22.7%
92/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
16.1%
64/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Rash
|
21.2%
86/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
25.4%
101/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
5.2%
21/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
6.0%
24/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Hypertension
|
12.1%
49/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
11.8%
47/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
|
Vascular disorders
Hypotension
|
5.9%
24/406 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
2.8%
11/397 • All-cause mortality was assessed from first dose to study completion (up to 105 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (approximately up to 107 months)
|
Additional Information
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