Trial Outcomes & Findings for A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma (NCT NCT01984242)
NCT ID: NCT01984242
Last Updated: 2019-12-23
Results Overview
Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
305 participants
Primary outcome timeframe
From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Results posted on
2019-12-23
Participant Flow
Total 305 participants enrolled in this study. Participants enrolled in atezolizumab (except European Union \[EU\] participants) or sunitinib group could crossover to receive atezolizumab and bevacizumab combination therapy in case of disease progression. Some participants didn't complete due to study termination, but study was completed as planned.
Participant milestones
| Measure |
Atezolizumab and Bevacizumab
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Atezolizumab
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Sunitinib
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
|---|---|---|---|
|
Overall Study
STARTED
|
101
|
103
|
101
|
|
Overall Study
Treated
|
101
|
103
|
100
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
101
|
103
|
101
|
Reasons for withdrawal
| Measure |
Atezolizumab and Bevacizumab
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Atezolizumab
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Sunitinib
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
|---|---|---|---|
|
Overall Study
Death
|
52
|
50
|
52
|
|
Overall Study
Withdrawal by Subject
|
5
|
3
|
10
|
|
Overall Study
Physician Decision
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
4
|
0
|
3
|
|
Overall Study
Sponsor Decision
|
1
|
0
|
0
|
|
Overall Study
Non-Compliance
|
1
|
0
|
0
|
|
Overall Study
Study terminated by Sponsor
|
38
|
50
|
34
|
|
Overall Study
Disease Progression
|
0
|
0
|
1
|
Baseline Characteristics
A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma
Baseline characteristics by cohort
| Measure |
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Total
n=305 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
61.1 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
60.1 years
STANDARD_DEVIATION 10.2 • n=7 Participants
|
59.7 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
60.3 years
STANDARD_DEVIATION 10.6 • n=4 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
75 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
74 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
230 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population
|
58.4 percentage of participants
|
59.2 percentage of participants
|
66.3 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population
|
8.4 months
Interval 7.0 to 14.0
|
6.1 months
Interval 5.4 to 13.6
|
11.7 months
Interval 8.4 to 17.3
|
—
|
PRIMARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population included ITT participants with programmed death-ligand 1 (PD-L1) expression of greater than or equal to (\>=) 1% on tumor-infiltrating immune cells.
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population
|
68.3 percentage of participants
|
59.3 percentage of participants
|
58.0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
|
7.8 months
Interval 3.8 to 10.8
|
5.5 months
Interval 3.0 to 13.9
|
14.7 months
Interval 8.2 to 25.1
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Biomarker evaluable population included ITT participants whose tumor samples had sufficient material available for gene signature expression analyses. Participants with higher than median expression of an immune gene signature were included in this analysis.
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Sunitinib
n=42 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=44 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=45 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
|
73.8 percentage of participants
|
61.4 percentage of participants
|
55.6 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Biomarker evaluable population. Participants with higher than median expression of an immune gene signature were included in this analysis.
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=42 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=44 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=45 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
|
7.1 months
Interval 4.2 to 8.7
|
5.7 months
Interval 3.2 to 16.7
|
17.5 months
Interval 10.3 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Biomarker evaluable population. Participants with higher than median expression of an immune gene signature were included in this analysis.
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Sunitinib
n=42 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=44 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=45 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
|
83.3 percentage of participants
|
77.3 percentage of participants
|
57.8 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Biomarker evaluable population. Participants with higher than median expression of an immune gene signature were included in this analysis.
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=42 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=44 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=45 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
|
6.8 months
Interval 5.4 to 8.7
|
5.5 months
Interval 3.0 to 11.1
|
16.6 months
Interval 8.2 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=55 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=61 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
|
65.0 percentage of participants
|
58.2 percentage of participants
|
59.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=55 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=61 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
|
8.2 months
Interval 5.7 to 11.4
|
5.7 months
Interval 5.4 to 17.3
|
13.8 months
Interval 8.3 to 25.1
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=55 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=61 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
|
78.3 percentage of participants
|
76.4 percentage of participants
|
63.9 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=55 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=61 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
|
7.1 months
Interval 5.8 to 11.3
|
5.5 months
Interval 3.0 to 10.9
|
11.1 months
Interval 8.1 to 19.3
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population
|
75.2 percentage of participants
|
75.7 percentage of participants
|
71.3 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population
|
7.8 months
Interval 5.7 to 11.2
|
5.5 months
Interval 3.0 to 8.4
|
11.1 months
Interval 8.2 to 13.5
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population
|
81.7 percentage of participants
|
74.1 percentage of participants
|
66.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
|
7.0 months
Interval 5.6 to 11.2
|
5.5 months
Interval 3.0 to 10.9
|
11.1 months
Interval 8.1 to 16.7
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to less than (\<) 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population
|
28.7 percentage of participants
Interval 20.15 to 38.57
|
25.2 percentage of participants
Interval 17.2 to 34.76
|
31.7 percentage of participants
Interval 22.78 to 41.69
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
|
26.7 percentage of participants
Interval 16.07 to 39.66
|
27.8 percentage of participants
Interval 16.46 to 41.64
|
46.0 percentage of participants
Interval 31.81 to 60.68
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population
|
32.7 percentage of participants
Interval 23.67 to 42.72
|
23.3 percentage of participants
Interval 15.54 to 32.66
|
34.7 percentage of participants
Interval 25.46 to 44.77
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
|
28.3 percentage of participants
Interval 17.45 to 41.44
|
25.9 percentage of participants
Interval 14.96 to 39.65
|
48.0 percentage of participants
Interval 33.66 to 62.58
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population
|
33.7 percentage of participants
Interval 24.56 to 43.75
|
25.2 percentage of participants
Interval 17.2 to 34.76
|
37.6 percentage of participants
Interval 28.18 to 47.82
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
|
30.0 percentage of participants
Interval 18.85 to 43.21
|
27.8 percentage of participants
Interval 16.46 to 41.64
|
52.0 percentage of participants
Interval 37.42 to 66.34
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population
|
63.4 percentage of participants
|
61.2 percentage of participants
|
60.4 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per Modified RECIST Via Investigator Assessment in ITT Population
|
9.9 months
Interval 8.1 to 14.1
|
10.9 months
Interval 7.9 to 14.0
|
16.7 months
Interval 11.4 to 22.6
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population
|
75.0 percentage of participants
|
59.3 percentage of participants
|
52.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
|
8.4 months
Interval 5.8 to 11.3
|
10.9 months
Interval 5.4 to 14.0
|
21.7 months
Interval 11.1 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Outcome measures
| Measure |
Sunitinib
n=29 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=26 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=32 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population
|
NA months
Data could not be estimated due to high number of censored participants.
|
NA months
Interval 23.4 to
Data could not be estimated due to high number of censored participants.
|
22.1 months
Interval 19.4 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Outcome measures
| Measure |
Sunitinib
n=33 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=24 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=35 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population
|
14.2 months
Interval 13.0 to
Data could not be estimated due to high number of censored participants.
|
NA months
Data could not be estimated due to high number of censored participants.
|
NA months
Interval 19.4 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Outcome measures
| Measure |
Sunitinib
n=16 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=15 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=23 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
|
NA months
Interval 12.0 to
Data could not be estimated due to high number of censored participants.
|
NA months
Interval 23.4 to
Data could not be estimated due to high number of censored participants.
|
22.1 months
Interval 19.4 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Outcome measures
| Measure |
Sunitinib
n=17 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=14 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=24 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
|
14.1 months
Interval 11.1 to
Data could not be estimated due to high number of censored participants.
|
NA months
Data could not be estimated due to high number of censored participants.
|
22.4 months
Interval 13.8 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.
Outcome measures
| Measure |
Sunitinib
n=34 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=26 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=38 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
DOR Per Modified RECIST Via Investigator Assessment in ITT Population
|
16.6 months
Interval 13.6 to
Data could not be estimated due to high number of censored participants.
|
NA months
Data could not be estimated due to high number of censored participants.
|
NA months
Interval 19.8 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.
Outcome measures
| Measure |
Sunitinib
n=18 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=15 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=26 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
|
16.6 months
Interval 11.3 to
Data could not be estimated due to high number of censored participants.
|
NA months
Data could not be estimated due to high number of censored participants.
|
22.4 months
Interval 19.4 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants Who Died in ITT Population
|
30.7 percentage of participants
|
35.0 percentage of participants
|
38.6 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: ITT population
OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.
Outcome measures
| Measure |
Sunitinib
n=101 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=103 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=101 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Overall Survival (OS) in ITT Population
|
NA months
Interval 27.2 to
Data could not be estimated due to high number of censored participants.
|
NA months
Interval 30.2 to
Data could not be estimated due to high number of censored participants.
|
NA months
Interval 23.9 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants Who Died in IC1/2/3 Population
|
35.0 percentage of participants
|
39.8 percentage of participants
|
38.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: IC1/2/3 population
OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.
Outcome measures
| Measure |
Sunitinib
n=60 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=50 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
OS in IC1/2/3 Population
|
NA months
Interval 22.4 to
Data could not be estimated due to high number of censored participants.
|
30.2 months
Interval 23.3 to
Data could not be estimated due to high number of censored participants.
|
27.3 months
Interval 24.6 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Crossover population included participants in atezolizumab or sunitinib arms who had crossed over to the atezolizumab and bevacizumab arm. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Outcome measures
| Measure |
Sunitinib
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=54 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=41 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population
|
—
|
27.8 percentage of participants
Interval 16.46 to 41.64
|
24.4 percentage of participants
Interval 12.36 to 40.3
|
—
|
SECONDARY outcome
Timeframe: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Crossover population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Outcome measures
| Measure |
Sunitinib
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=15 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=10 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population
|
—
|
NA months
Interval 11.1 to
Data could not be estimated due to high number of censored participants.
|
NA months
Interval 7.2 to
Data could not be estimated due to high number of censored participants.
|
—
|
SECONDARY outcome
Timeframe: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Crossover population
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Sunitinib
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=57 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=44 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population
|
—
|
68.4 percentage of participants
|
59.1 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)Population: Crossover population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Outcome measures
| Measure |
Sunitinib
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=57 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=44 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population
|
—
|
8.3 months
Interval 3.1 to 11.2
|
12.6 months
Interval 6.0 to 17.7
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 until treatment discontinuation (until data cut-off date 17 October 2016, up to approximately 2.75 years) (1 cycle=6 weeks)Population: ATA evaluable population included participants at baseline who had a baseline ATA sample and post-baseline participants who had at least one ATA sample and had received at least one dose of study treatment.
This outcome measure was planned to be analyzed in 'Atezolizumab' and 'Atezolizumab and Bevacizumab' arms only.
Outcome measures
| Measure |
Sunitinib
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=96 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=97 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab
|
—
|
25.0 percentage of participants
|
34.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: 30 minutes after end of infusion on Cycle 1 Day 1 (1 cycle=6 weeks) (infusion length for first dose=60 minutes)Population: The pharmacokinetic (PK) evaluable population included participants who received at least one dose of study drug and had sufficient PK sample collected within the time specified in the protocol. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
Outcome measures
| Measure |
Sunitinib
n=41 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=93 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=95 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
n=53 Participants
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Maximum Serum Concentration (Cmax) of Atezolizumab
|
418 micrograms per milliliter (mcg/mL)
Standard Deviation 114
|
358 micrograms per milliliter (mcg/mL)
Standard Deviation 93.1
|
335 micrograms per milliliter (mcg/mL)
Standard Deviation 86.0
|
314 micrograms per milliliter (mcg/mL)
Standard Deviation 87.1
|
SECONDARY outcome
Timeframe: Pre-infusion (0 hour) on Day 1 of Cycles 2 and 4; Day 22 of Cycles 1, 2, and 4 (1 cycle=6 weeks) (infusion length=30-60 minutes)Population: PK evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure. 'Number Analyzed'=participants evaluable for this outcome measure at specified timepoint for each arm respectively.
Outcome measures
| Measure |
Sunitinib
n=42 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=94 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=98 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
n=52 Participants
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Minimum Serum Concentration (Cmin) of Atezolizumab
Cycle 1 Day 22
|
174 mcg/mL
Standard Deviation 121
|
79.9 mcg/mL
Standard Deviation 26.1
|
72.6 mcg/mL
Standard Deviation 29.5
|
73.2 mcg/mL
Standard Deviation 31.5
|
|
Minimum Serum Concentration (Cmin) of Atezolizumab
Cycle 2 Day 1
|
158 mcg/mL
Standard Deviation 101
|
125 mcg/mL
Standard Deviation 47.4
|
122 mcg/mL
Standard Deviation 50.4
|
106 mcg/mL
Standard Deviation 45.2
|
|
Minimum Serum Concentration (Cmin) of Atezolizumab
Cycle 2 Day 22
|
164 mcg/mL
Standard Deviation 70.7
|
159 mcg/mL
Standard Deviation 84.6
|
152 mcg/mL
Standard Deviation 65.3
|
141 mcg/mL
Standard Deviation 85.5
|
|
Minimum Serum Concentration (Cmin) of Atezolizumab
Cycle 4 Day 1
|
154 mcg/mL
Standard Deviation 62.7
|
192 mcg/mL
Standard Deviation 77.6
|
183 mcg/mL
Standard Deviation 90.5
|
174 mcg/mL
Standard Deviation 75.7
|
|
Minimum Serum Concentration (Cmin) of Atezolizumab
Cycle 4 Day 22
|
163 mcg/mL
Standard Deviation 70.5
|
200 mcg/mL
Standard Deviation 90.0
|
190 mcg/mL
Standard Deviation 86.3
|
172 mcg/mL
Standard Deviation 78.8
|
SECONDARY outcome
Timeframe: 30 minutes after end of infusion on Day 1 of Cycles 1 and 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)Population: PK evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
Outcome measures
| Measure |
Sunitinib
n=44 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=34 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=86 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Cmax of Bevacizumab
|
455 mcg/mL
Standard Deviation 106
|
433 mcg/mL
Standard Deviation 115
|
89.8 mcg/mL
Standard Deviation 39.4
|
—
|
SECONDARY outcome
Timeframe: For Atezolizumab and Bevacizumab Arm: at First-line treatment discontinuation (up to approximately 2.75 years); For Crossover Arms: pre-infusion (0 hour) on Day 1 of Cycle 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)Population: PK evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
Outcome measures
| Measure |
Sunitinib
n=42 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=39 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=42 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Cmin of Bevacizumab
|
95.9 mcg/mL
Standard Deviation 43.9
|
101 mcg/mL
Standard Deviation 48.7
|
75.2 mcg/mL
Standard Deviation 72.1
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)Population: Patient Reported Outcome (PRO)-evaluable population: randomized participants who had non-missing baseline assessment and at least 1 post-baseline assessment. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome. 'Number Analyzed'=participants evaluable for this outcome at specified timepoint for each arm, respectively.
MDASI questionnaire comprises of 2 parts: symptoms (16 items), interference with daily life (6 items). Participants were asked to rate how much their symptoms interfered with general activity, mood, work, relations with other people, walking, and enjoyment of life during the last 24 hours. Each item in the interference score was answered on a scale of 0 (did not interfere) to 10 (interfered completely). The mean score of all 6 items was reported on the scale of 0 (did not interfere) to 10 (interfered completely).
Outcome measures
| Measure |
Sunitinib
n=93 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=95 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=96 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 1 Day 1
|
1.79 units on a scale
Standard Deviation 2.39
|
1.38 units on a scale
Standard Deviation 2.03
|
1.60 units on a scale
Standard Deviation 1.97
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 1 Day 22
|
3.16 units on a scale
Standard Deviation 2.65
|
1.26 units on a scale
Standard Deviation 2.07
|
2.08 units on a scale
Standard Deviation 2.34
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 2 Day 1
|
1.83 units on a scale
Standard Deviation 2.19
|
1.20 units on a scale
Standard Deviation 1.72
|
1.56 units on a scale
Standard Deviation 1.82
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 2 Day 22
|
2.50 units on a scale
Standard Deviation 2.47
|
1.04 units on a scale
Standard Deviation 1.62
|
1.57 units on a scale
Standard Deviation 1.83
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 3 Day 1
|
1.49 units on a scale
Standard Deviation 2.01
|
0.90 units on a scale
Standard Deviation 1.43
|
1.72 units on a scale
Standard Deviation 2.15
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 3 Day 22
|
2.20 units on a scale
Standard Deviation 2.42
|
1.01 units on a scale
Standard Deviation 1.58
|
1.66 units on a scale
Standard Deviation 2.07
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 4 Day 1
|
1.61 units on a scale
Standard Deviation 2.24
|
1.24 units on a scale
Standard Deviation 1.99
|
1.59 units on a scale
Standard Deviation 2.11
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 4 Day 22
|
1.92 units on a scale
Standard Deviation 2.00
|
1.26 units on a scale
Standard Deviation 1.98
|
1.68 units on a scale
Standard Deviation 2.31
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 5 Day 1
|
1.53 units on a scale
Standard Deviation 1.96
|
0.69 units on a scale
Standard Deviation 1.11
|
1.70 units on a scale
Standard Deviation 2.29
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 5 Day 22
|
1.97 units on a scale
Standard Deviation 2.21
|
0.67 units on a scale
Standard Deviation 1.33
|
1.80 units on a scale
Standard Deviation 2.29
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 6 Day 1
|
1.39 units on a scale
Standard Deviation 1.76
|
0.64 units on a scale
Standard Deviation 1.13
|
1.91 units on a scale
Standard Deviation 2.54
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 6 Day 22
|
2.00 units on a scale
Standard Deviation 2.23
|
0.63 units on a scale
Standard Deviation 1.12
|
1.80 units on a scale
Standard Deviation 2.38
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 7 Day 1
|
1.00 units on a scale
Standard Deviation 1.09
|
0.53 units on a scale
Standard Deviation 0.78
|
1.99 units on a scale
Standard Deviation 2.49
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 7 Day 22
|
1.15 units on a scale
Standard Deviation 1.04
|
0.59 units on a scale
Standard Deviation 0.93
|
2.01 units on a scale
Standard Deviation 2.45
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 8 Day 1
|
0.94 units on a scale
Standard Deviation 1.04
|
0.55 units on a scale
Standard Deviation 0.85
|
1.88 units on a scale
Standard Deviation 2.26
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 8 Day 22
|
1.34 units on a scale
Standard Deviation 1.39
|
0.58 units on a scale
Standard Deviation 0.91
|
1.81 units on a scale
Standard Deviation 2.41
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 9 Day 1
|
1.16 units on a scale
Standard Deviation 1.22
|
0.55 units on a scale
Standard Deviation 0.90
|
1.75 units on a scale
Standard Deviation 2.24
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 9 Day 22
|
1.57 units on a scale
Standard Deviation 1.61
|
0.58 units on a scale
Standard Deviation 0.89
|
1.64 units on a scale
Standard Deviation 2.16
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 10 Day 1
|
1.08 units on a scale
Standard Deviation 1.40
|
0.81 units on a scale
Standard Deviation 1.13
|
1.43 units on a scale
Standard Deviation 1.82
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 10 Day 22
|
1.49 units on a scale
Standard Deviation 1.78
|
0.70 units on a scale
Standard Deviation 1.10
|
1.55 units on a scale
Standard Deviation 2.09
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 11 Day 1
|
0.98 units on a scale
Standard Deviation 1.00
|
0.61 units on a scale
Standard Deviation 0.95
|
1.65 units on a scale
Standard Deviation 2.13
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 11 Day 22
|
1.47 units on a scale
Standard Deviation 1.61
|
0.78 units on a scale
Standard Deviation 1.07
|
1.35 units on a scale
Standard Deviation 1.81
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 12 Day 1
|
0.84 units on a scale
Standard Deviation 0.83
|
0.68 units on a scale
Standard Deviation 1.15
|
1.21 units on a scale
Standard Deviation 1.69
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 12 Day 22
|
1.41 units on a scale
Standard Deviation 1.53
|
0.53 units on a scale
Standard Deviation 0.99
|
1.51 units on a scale
Standard Deviation 2.23
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 13 Day 1
|
1.26 units on a scale
Standard Deviation 1.45
|
0.68 units on a scale
Standard Deviation 1.07
|
1.50 units on a scale
Standard Deviation 2.16
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 13 Day 22
|
1.32 units on a scale
Standard Deviation 1.37
|
0.67 units on a scale
Standard Deviation 1.10
|
1.45 units on a scale
Standard Deviation 2.32
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 14 Day 1
|
1.07 units on a scale
Standard Deviation 1.31
|
0.67 units on a scale
Standard Deviation 0.95
|
1.60 units on a scale
Standard Deviation 2.24
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 14 Day 22
|
1.50 units on a scale
Standard Deviation 1.48
|
0.63 units on a scale
Standard Deviation 0.94
|
1.40 units on a scale
Standard Deviation 2.09
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 15 Day 1
|
1.50 units on a scale
Standard Deviation 1.64
|
0.84 units on a scale
Standard Deviation 1.16
|
1.16 units on a scale
Standard Deviation 1.74
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 15 Day 22
|
2.08 units on a scale
Standard Deviation 1.64
|
0.71 units on a scale
Standard Deviation 1.10
|
1.48 units on a scale
Standard Deviation 1.92
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 16 Day 1
|
1.07 units on a scale
Standard Deviation 1.22
|
0.85 units on a scale
Standard Deviation 1.40
|
0.87 units on a scale
Standard Deviation 0.99
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 16 Day 22
|
2.04 units on a scale
Standard Deviation 2.24
|
0.87 units on a scale
Standard Deviation 1.30
|
0.72 units on a scale
Standard Deviation 0.93
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 17 Day 1
|
0.71 units on a scale
Standard Deviation 0.95
|
0.57 units on a scale
Standard Deviation 0.75
|
0.98 units on a scale
Standard Deviation 0.99
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 17 Day 22
|
1.21 units on a scale
Standard Deviation 1.32
|
0.65 units on a scale
Standard Deviation 0.97
|
0.73 units on a scale
Standard Deviation 1.02
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 18 Day 1
|
0.95 units on a scale
Standard Deviation 1.15
|
0.71 units on a scale
Standard Deviation 0.98
|
0.93 units on a scale
Standard Deviation 1.07
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 18 Day 22
|
1.05 units on a scale
Standard Deviation 1.42
|
0.33 units on a scale
Standard Deviation 0.41
|
0.79 units on a scale
Standard Deviation 1.06
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 19 Day 1
|
1.33 units on a scale
Standard Deviation 1.66
|
0.31 units on a scale
Standard Deviation 0.34
|
1.11 units on a scale
Standard Deviation 1.25
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 19 Day 22
|
1.55 units on a scale
Standard Deviation 1.69
|
0.30 units on a scale
Standard Deviation 0.41
|
0.97 units on a scale
Standard Deviation 1.37
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 20 Day 1
|
0.90 units on a scale
Standard Deviation 1.07
|
0.21 units on a scale
Standard Deviation 0.42
|
1.19 units on a scale
Standard Deviation 1.31
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 20 Day 22
|
1.67 units on a scale
Standard Deviation 1.56
|
0.04 units on a scale
Standard Deviation 0.08
|
1.10 units on a scale
Standard Deviation 1.30
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 21 Day 1
|
0.78 units on a scale
Standard Deviation 1.07
|
0.00 units on a scale
Standard Deviation 0.00
|
1.17 units on a scale
Standard Deviation 1.42
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 21 Day 22
|
1.25 units on a scale
Standard Deviation 1.53
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
1.23 units on a scale
Standard Deviation 1.51
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 22 Day 1
|
0.83 units on a scale
Standard Deviation 0.71
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
0.54 units on a scale
Standard Deviation 0.76
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 22 Day 22
|
1.25 units on a scale
Standard Deviation 1.53
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
0.94 units on a scale
Standard Deviation 1.07
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 23 Day 1
|
1.58 units on a scale
Standard Deviation 2.00
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
1.67 units on a scale
Standard Deviation 1.89
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 23 Day 22
|
2.67 units on a scale
Standard Deviation 2.36
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
1.25 units on a scale
Standard Deviation 1.77
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 24 Day 1
|
1.67 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
2.33 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 24 Day 22
|
0.50 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
—
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Cycle 25 Day 1
|
—
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
—
|
—
|
|
M.D. Anderson Symptom Inventory (MDASI) Interference Score
Treatment discontinuation
|
3.49 units on a scale
Standard Deviation 3.16
|
2.29 units on a scale
Standard Deviation 2.54
|
2.54 units on a scale
Standard Deviation 2.66
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)Population: PRO-evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure. 'Number Analyzed'=participants evaluable for this outcome measure at specified timepoint for each arm respectively.
BFI questionnaire comprises of 2 parts: fatigue level (3 items), interference with daily life (1 item with 6 sub-items). Each items in the fatigue level score was answered on a scale of 0 (no fatigue) to 10 (as bad as you can imagine). The mean score of all 3 items was reported on the scale of 0 (no fatigue) to 10 (as bad as you can imagine).
Outcome measures
| Measure |
Sunitinib
n=93 Participants
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab
n=94 Participants
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab and Bevacizumab
n=95 Participants
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Sunitinib (Crossover)
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 21 Day 1
|
1.67 units on a scale
Standard Deviation 1.53
|
2.50 units on a scale
Standard Deviation 3.54
|
2.60 units on a scale
Standard Deviation 2.97
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 1 Day 1
|
2.66 units on a scale
Standard Deviation 2.74
|
2.52 units on a scale
Standard Deviation 2.72
|
2.80 units on a scale
Standard Deviation 2.64
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 1 Day 22
|
4.42 units on a scale
Standard Deviation 3.09
|
2.55 units on a scale
Standard Deviation 2.60
|
3.80 units on a scale
Standard Deviation 2.86
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 2 Day 1
|
2.86 units on a scale
Standard Deviation 2.76
|
2.63 units on a scale
Standard Deviation 2.69
|
3.21 units on a scale
Standard Deviation 2.61
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 2 Day 22
|
3.69 units on a scale
Standard Deviation 2.74
|
2.57 units on a scale
Standard Deviation 2.74
|
3.15 units on a scale
Standard Deviation 2.61
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 3 Day 1
|
2.35 units on a scale
Standard Deviation 2.44
|
2.11 units on a scale
Standard Deviation 2.42
|
2.91 units on a scale
Standard Deviation 2.60
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 3 Day 22
|
3.60 units on a scale
Standard Deviation 3.09
|
2.31 units on a scale
Standard Deviation 2.71
|
2.93 units on a scale
Standard Deviation 2.67
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 4 Day 1
|
2.39 units on a scale
Standard Deviation 2.47
|
2.32 units on a scale
Standard Deviation 2.86
|
3.21 units on a scale
Standard Deviation 2.66
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 4 Day 22
|
3.15 units on a scale
Standard Deviation 2.57
|
2.33 units on a scale
Standard Deviation 2.94
|
3.06 units on a scale
Standard Deviation 2.68
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 5 Day 1
|
2.32 units on a scale
Standard Deviation 2.62
|
1.59 units on a scale
Standard Deviation 2.03
|
2.97 units on a scale
Standard Deviation 2.83
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 5 Day 22
|
2.91 units on a scale
Standard Deviation 2.86
|
1.34 units on a scale
Standard Deviation 1.81
|
3.02 units on a scale
Standard Deviation 2.87
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 6 Day 1
|
2.22 units on a scale
Standard Deviation 2.48
|
1.42 units on a scale
Standard Deviation 1.90
|
3.05 units on a scale
Standard Deviation 2.83
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 6 Day 22
|
3.09 units on a scale
Standard Deviation 2.69
|
1.39 units on a scale
Standard Deviation 2.01
|
3.23 units on a scale
Standard Deviation 2.94
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 7 Day 1
|
1.68 units on a scale
Standard Deviation 1.75
|
1.33 units on a scale
Standard Deviation 1.91
|
3.16 units on a scale
Standard Deviation 2.81
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 7 Day 22
|
2.16 units on a scale
Standard Deviation 1.87
|
1.24 units on a scale
Standard Deviation 1.67
|
2.86 units on a scale
Standard Deviation 2.60
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 8 Day 1
|
1.72 units on a scale
Standard Deviation 1.70
|
1.12 units on a scale
Standard Deviation 1.68
|
2.80 units on a scale
Standard Deviation 2.56
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 8 Day 22
|
2.58 units on a scale
Standard Deviation 2.13
|
1.24 units on a scale
Standard Deviation 1.75
|
2.88 units on a scale
Standard Deviation 2.80
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 9 Day 1
|
2.12 units on a scale
Standard Deviation 2.48
|
1.11 units on a scale
Standard Deviation 1.55
|
3.09 units on a scale
Standard Deviation 2.81
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 9 Day 22
|
2.64 units on a scale
Standard Deviation 2.57
|
1.19 units on a scale
Standard Deviation 1.71
|
2.80 units on a scale
Standard Deviation 2.73
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 10 Day 1
|
2.11 units on a scale
Standard Deviation 2.23
|
1.29 units on a scale
Standard Deviation 1.88
|
2.80 units on a scale
Standard Deviation 2.58
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 10 Day 22
|
2.24 units on a scale
Standard Deviation 2.43
|
1.33 units on a scale
Standard Deviation 1.90
|
2.91 units on a scale
Standard Deviation 2.83
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 11 Day 1
|
1.93 units on a scale
Standard Deviation 1.65
|
1.40 units on a scale
Standard Deviation 1.96
|
2.98 units on a scale
Standard Deviation 2.71
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 11 Day 22
|
2.42 units on a scale
Standard Deviation 2.12
|
1.72 units on a scale
Standard Deviation 2.23
|
2.59 units on a scale
Standard Deviation 2.44
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 12 Day 1
|
1.66 units on a scale
Standard Deviation 1.67
|
1.25 units on a scale
Standard Deviation 1.96
|
2.31 units on a scale
Standard Deviation 2.25
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 12 Day 22
|
2.27 units on a scale
Standard Deviation 2.05
|
1.44 units on a scale
Standard Deviation 2.12
|
2.79 units on a scale
Standard Deviation 2.46
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 13 Day 1
|
2.08 units on a scale
Standard Deviation 1.56
|
1.65 units on a scale
Standard Deviation 2.17
|
2.69 units on a scale
Standard Deviation 2.57
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 13 Day 22
|
2.60 units on a scale
Standard Deviation 2.28
|
1.55 units on a scale
Standard Deviation 2.13
|
2.97 units on a scale
Standard Deviation 2.97
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 14 Day 1
|
2.30 units on a scale
Standard Deviation 2.34
|
1.45 units on a scale
Standard Deviation 2.14
|
2.94 units on a scale
Standard Deviation 2.94
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 21 Day 22
|
2.00 units on a scale
Standard Deviation 1.41
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
2.40 units on a scale
Standard Deviation 1.95
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 14 Day 22
|
2.60 units on a scale
Standard Deviation 2.09
|
1.61 units on a scale
Standard Deviation 2.00
|
2.83 units on a scale
Standard Deviation 2.85
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 15 Day 1
|
2.60 units on a scale
Standard Deviation 2.33
|
1.76 units on a scale
Standard Deviation 2.19
|
2.73 units on a scale
Standard Deviation 2.56
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 15 Day 22
|
2.94 units on a scale
Standard Deviation 1.61
|
0.92 units on a scale
Standard Deviation 1.12
|
2.61 units on a scale
Standard Deviation 2.79
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 16 Day 1
|
2.21 units on a scale
Standard Deviation 2.42
|
1.54 units on a scale
Standard Deviation 2.07
|
1.88 units on a scale
Standard Deviation 1.99
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 16 Day 22
|
2.85 units on a scale
Standard Deviation 2.19
|
2.11 units on a scale
Standard Deviation 2.15
|
1.70 units on a scale
Standard Deviation 1.61
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 17 Day 1
|
1.50 units on a scale
Standard Deviation 1.51
|
1.60 units on a scale
Standard Deviation 1.96
|
1.78 units on a scale
Standard Deviation 1.59
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 17 Day 22
|
2.38 units on a scale
Standard Deviation 1.60
|
2.13 units on a scale
Standard Deviation 2.42
|
2.00 units on a scale
Standard Deviation 1.80
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 18 Day 1
|
1.71 units on a scale
Standard Deviation 1.70
|
1.88 units on a scale
Standard Deviation 2.23
|
2.23 units on a scale
Standard Deviation 1.74
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 18 Day 22
|
2.14 units on a scale
Standard Deviation 2.19
|
1.67 units on a scale
Standard Deviation 2.07
|
1.92 units on a scale
Standard Deviation 2.14
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 19 Day 1
|
2.29 units on a scale
Standard Deviation 3.30
|
1.50 units on a scale
Standard Deviation 1.97
|
2.17 units on a scale
Standard Deviation 2.48
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 19 Day 22
|
3.29 units on a scale
Standard Deviation 2.43
|
1.40 units on a scale
Standard Deviation 2.19
|
1.90 units on a scale
Standard Deviation 2.42
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 20 Day 1
|
1.80 units on a scale
Standard Deviation 1.30
|
1.25 units on a scale
Standard Deviation 2.50
|
3.00 units on a scale
Standard Deviation 3.16
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 20 Day 22
|
2.25 units on a scale
Standard Deviation 2.06
|
1.50 units on a scale
Standard Deviation 3.00
|
2.40 units on a scale
Standard Deviation 3.05
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 22 Day 1
|
2.00 units on a scale
Standard Deviation 1.41
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
1.25 units on a scale
Standard Deviation 1.89
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 22 Day 22
|
3.00 units on a scale
Standard Deviation 2.83
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
1.33 units on a scale
Standard Deviation 2.31
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 23 Day 1
|
2.00 units on a scale
Standard Deviation 2.83
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
2.50 units on a scale
Standard Deviation 3.54
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 23 Day 22
|
4.50 units on a scale
Standard Deviation 3.54
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
2.00 units on a scale
Standard Deviation 2.83
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 24 Day 1
|
2.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
4.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 24 Day 22
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
—
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Cycle 25 Day 1
|
—
|
0.00 units on a scale
Standard Deviation NA
Standard deviation was not estimable for single evaluable participant.
|
—
|
—
|
|
Brief Fatigue Inventory (BFI) Fatigue Level Score
Treatment discontinuation
|
3.75 units on a scale
Standard Deviation 3.09
|
3.95 units on a scale
Standard Deviation 3.27
|
3.74 units on a scale
Standard Deviation 2.82
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)Population: As this outcome was pre-specified as an exploratory outcome, no results are reported.
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Outcome measures
Outcome data not reported
Adverse Events
Atezolizumab and Bevacizumab
Serious events: 49 serious events
Other events: 99 other events
Deaths: 0 deaths
Atezolizumab
Serious events: 37 serious events
Other events: 94 other events
Deaths: 0 deaths
Sunitinib
Serious events: 28 serious events
Other events: 99 other events
Deaths: 0 deaths
Atezolizumab (Crossover)
Serious events: 15 serious events
Other events: 44 other events
Deaths: 0 deaths
Sunitinib (Crossover)
Serious events: 22 serious events
Other events: 57 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Atezolizumab and Bevacizumab
n=101 participants at risk
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Atezolizumab
n=103 participants at risk
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Sunitinib
n=100 participants at risk
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab (Crossover)
n=46 participants at risk
Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
Sunitinib (Crossover)
n=63 participants at risk
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Cardiac disorders
Angina pectoris
|
2.0%
2/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Cardiac disorders
Atrial fibrillation
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Cardiac disorders
Myocardial infarction
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Cardiac disorders
Tachycardia
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Ear and labyrinth disorders
Vertigo
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Endocrine disorders
Adrenal insufficiency
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.3%
2/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Ascites
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Autoimmune pancreatitis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Diarrhoea
|
4.0%
4/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Gastrointestinal inflammation
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Mesenteric vein thrombosis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.8%
3/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Pancreatic fistula
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Retroperitoneal haemorrhage
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Vomiting
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Chest pain
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Fatigue
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
General physical health deterioration
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Pain
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.8%
3/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Pyrexia
|
2.0%
2/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.9%
4/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Sudden death
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Hepatobiliary disorders
Bile duct stenosis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Hepatobiliary disorders
Hepatorenal syndrome
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Arthritis infective
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Bacteraemia
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Bronchitis
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Chest wall abscess
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Diverticulitis
|
3.0%
3/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Gastroenteritis
|
2.0%
2/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Influenza
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.9%
3/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Meningitis viral
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Necrotising fasciitis
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Pancreatic abscess
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Paronychia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Peritonitis bacterial
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Pneumonia
|
3.0%
3/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Sinusitis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Spinal cord infection
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Staphylococcal infection
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Urinary tract infection
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Wound infection
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Injury, poisoning and procedural complications
Fall
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Blood creatinine increased
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.0%
2/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.8%
3/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
4.0%
4/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.9%
5/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Fracture pain
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Muscle haemorrhage
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.3%
2/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Neuropathic arthropathy
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
2.0%
2/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial tumour haemorrhage
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Amnesia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Autoimmune neuropathy
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Demyelination
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Facial paralysis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Headache
|
2.0%
2/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Nerve root compression
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Peripheral sensorimotor neuropathy
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Syncope
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Psychiatric disorders
Depression
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.9%
3/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Renal and urinary disorders
Haematuria
|
3.0%
3/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.3%
2/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Renal and urinary disorders
Urethral stenosis
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.9%
4/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal mass
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Obstructive airways disorder
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
3.0%
3/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Surgical and medical procedures
Limb Operation
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Vascular disorders
Deep vein thrombosis
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Vascular disorders
Embolism
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Vascular disorders
Haemorrhage
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Vascular disorders
Hypertension
|
4.0%
4/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Colitis microscopic
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Obstructive pancreatitis
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Asthenia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Death
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Oedema
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Immune system disorders
Haemophagocytic lymphohistiocytosis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Abscess
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Biliary sepsis
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Psoas abscess
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Sepsis
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Skin infection
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Asparate aminotransferase increased
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Intracranial haematoma
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Paresis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
Other adverse events
| Measure |
Atezolizumab and Bevacizumab
n=101 participants at risk
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
|
Atezolizumab
n=103 participants at risk
Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Sunitinib
n=100 participants at risk
Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
|
Atezolizumab (Crossover)
n=46 participants at risk
Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
Sunitinib (Crossover)
n=63 participants at risk
Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.9%
11/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
18.4%
19/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
18.0%
18/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.3%
2/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
14.3%
9/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.0%
9/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.0%
2/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
12.0%
12/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.9%
6/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.0%
15/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.3%
2/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Endocrine disorders
Hypothyroidism
|
18.8%
19/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.7%
12/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
20.0%
20/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.4%
8/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.1%
7/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Abdominal distension
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.0%
3/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.9%
5/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.1%
7/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Abdominal pain
|
16.8%
17/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.8%
8/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
16.0%
16/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
21.7%
10/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
23.8%
15/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.0%
4/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.0%
9/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Constipation
|
29.7%
30/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.5%
16/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
30.0%
30/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
19.6%
9/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
22.2%
14/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Diarrhoea
|
35.6%
36/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
19.4%
20/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
62.0%
62/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
28.3%
13/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
30.2%
19/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Dry mouth
|
11.9%
12/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.7%
12/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.0%
9/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.9%
5/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.9%
5/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Dyspepsia
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.9%
4/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
20.0%
20/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.9%
7/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.9%
3/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
13.0%
13/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Gingival bleeding
|
6.9%
7/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Nausea
|
39.6%
40/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
18.4%
19/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
46.0%
46/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
30.4%
14/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
33.3%
21/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Oral pain
|
4.0%
4/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.0%
7/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Stomatitis
|
14.9%
15/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.9%
3/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
25.0%
25/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
13.0%
6/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.9%
5/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Vomiting
|
19.8%
20/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.8%
8/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
21.0%
21/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
13.0%
6/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
25.4%
16/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Asthenia
|
6.9%
7/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.8%
8/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.0%
7/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.1%
7/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Chest pain
|
6.9%
7/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.9%
5/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.0%
6/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
4/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Chills
|
5.0%
5/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.8%
8/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
13.0%
13/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Fatigue
|
61.4%
62/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
50.5%
52/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
70.0%
70/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
41.3%
19/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
42.9%
27/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Influenza like illness
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
5.8%
6/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.0%
3/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Mucosal inflammation
|
17.8%
18/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.9%
4/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
33.0%
33/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
13.0%
6/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Oedema peripheral
|
19.8%
20/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.7%
12/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.0%
10/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.4%
8/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.9%
10/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Pain
|
15.8%
16/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.8%
7/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.0%
10/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
General disorders
Pyrexia
|
18.8%
19/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
22.3%
23/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.0%
10/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
13.0%
6/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.9%
10/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Nasopharyngitis
|
10.9%
11/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.8%
8/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Rhinitis
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
5.8%
6/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.0%
1/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Sinusitis
|
14.9%
15/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.9%
5/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.0%
3/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
4/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Upper respiratory tract infection
|
13.9%
14/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.7%
11/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
5.0%
5/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.4%
8/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Urinary tract infection
|
9.9%
10/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.8%
8/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.0%
3/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Alanine aminotransferase increased
|
13.9%
14/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.8%
7/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.0%
15/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Aspartate aminotransferase increased
|
9.9%
10/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.8%
7/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.0%
17/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Blood alkaline phosphatase increased
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.9%
3/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.0%
6/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Blood creatinine increased
|
12.9%
13/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
16.5%
17/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
14.0%
14/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
21.7%
10/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
12.7%
8/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Platelet count decreased
|
2.0%
2/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.0%
6/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Weight decreased
|
17.8%
18/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.9%
5/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.0%
10/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.3%
2/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.5%
6/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.8%
3/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Investigations
Protein total increased
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
22.8%
23/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.7%
11/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
30.0%
30/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
4/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
23.8%
15/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Dehydration
|
10.9%
11/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.9%
5/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.0%
4/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.5%
6/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
9.9%
10/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.9%
4/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.0%
4/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
12.6%
13/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
5.0%
5/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.9%
5/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.9%
5/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
14.9%
15/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
5.8%
6/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.0%
6/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
4/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
5.9%
6/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
5.0%
5/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
9.9%
10/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.0%
6/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.3%
2/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
11.9%
12/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.9%
5/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.0%
7/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.9%
5/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.9%
10/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.9%
6/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.7%
11/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.0%
11/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
4/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
39.6%
40/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
18.4%
19/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
19.0%
19/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
37.0%
17/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
23.8%
15/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
18.8%
19/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.5%
18/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
20.0%
20/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.4%
8/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.5%
11/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.0%
6/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
4/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
21.8%
22/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.7%
10/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.0%
6/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
19.6%
9/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.9%
5/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.9%
12/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.7%
10/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.0%
15/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.1%
7/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
9.9%
10/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.9%
5/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.0%
8/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.8%
17/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.8%
8/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.0%
17/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
19.6%
9/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.5%
6/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Dizziness
|
12.9%
13/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
9/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
13.0%
13/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
4/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.5%
6/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Dysgeusia
|
11.9%
12/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.9%
3/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
30.0%
30/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Headache
|
34.7%
35/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.5%
16/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
23.0%
23/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.2%
7/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
20.6%
13/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Neuropathy peripheral
|
5.0%
5/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.97%
1/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
5.0%
5/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Nervous system disorders
Paraesthesia
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.8%
8/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.0%
11/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Psychiatric disorders
Depression
|
8.9%
9/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.9%
5/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.0%
7/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.3%
2/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Psychiatric disorders
Insomnia
|
9.9%
10/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.8%
7/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
12.0%
12/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
12.7%
8/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Renal and urinary disorders
Dysuria
|
0.99%
1/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.8%
7/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Renal and urinary disorders
Haematuria
|
3.0%
3/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.7%
10/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.0%
9/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
4/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Renal and urinary disorders
Proteinuria
|
37.6%
38/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.7%
10/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.0%
9/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
45.7%
21/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
39.7%
25/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Renal and urinary disorders
Nocturia
|
5.9%
6/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.0%
4/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
23.8%
24/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
25.2%
26/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
25.0%
25/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
30.4%
14/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
19.0%
12/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
17.8%
18/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.0%
4/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
19.6%
9/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
12.7%
8/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
18.8%
19/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.5%
18/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
18.0%
18/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.4%
8/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
15.9%
10/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
5.0%
5/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.8%
7/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.0%
8/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
28.7%
29/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
12.0%
12/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
28.3%
13/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.9%
5/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
11.9%
12/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.7%
11/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.0%
3/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.9%
5/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
11.9%
12/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.7%
11/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.0%
3/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
13.0%
6/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.9%
5/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.9%
6/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
5.8%
6/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.0%
3/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
12.9%
13/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
14.6%
15/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.0%
10/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.9%
5/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.9%
5/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
7.0%
7/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
8.7%
4/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
4.8%
3/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
3.0%
3/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
41.0%
41/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
26.7%
27/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.5%
18/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
10.0%
10/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
17.4%
8/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.1%
7/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Rash
|
27.7%
28/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
23.3%
24/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
14.0%
14/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
26.1%
12/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
11.1%
7/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.3%
4/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Vascular disorders
Hypertension
|
37.6%
38/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.7%
10/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
34.0%
34/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
26.1%
12/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
20.6%
13/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.6%
1/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
3.2%
2/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Psychiatric disorders
Anxiety
|
7.9%
8/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
5.8%
6/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.0%
6/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.2%
1/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
9.5%
6/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
6.9%
7/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
1.9%
2/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
2.0%
2/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
|
Eye disorders
Dry eye
|
0.00%
0/101 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/103 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/100 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
6.5%
3/46 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
|
0.00%
0/63 • Baseline up to approximately 60 months.
Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER