Trial Outcomes & Findings for A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer (NCT NCT03337724)
NCT ID: NCT03337724
Last Updated: 2024-03-12
Results Overview
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1), or death from any cause, whichever occurred first, assessed up to 27 months for this outcome measure. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
579 participants
Primary outcome timeframe
From randomization up to 27 months
Results posted on
2024-03-12
Participant Flow
Participants with protocol specified triple-negative breast cancer (TNBC) or HR+/HER- took part in the study in the following countries: Argentina, Australia, Belgium, Brazil, Canada, Chile, Costa Rica, Czech Republic, France, Greece, Germany, Hungary, Italy, India, Japan, Macedonia, Mexico, Poland, Peru, Republic of Korea, Russian Federation, Slovenia, Spain, Singapore, South Africa, Taiwan, Turkey, Ukraine, United Kingdom, and United States from 6 January 2018 to 4 January 2023.
Participants with TNBC or hormone receptor positive(HR+)/human epidermal growth factor receptor 2 negative(HER2-) breast adenocarcinoma with phosphatidylinositol-4,5-bisphosphate3-kinase,catalytic subunit, alpha(PIK3CA)/serine-threonine kinase(AKT1)/phosphatase \& tensin homolog (PTEN)-altered tumor were randomized to ipatasertib 400 mg+paclitaxel or placebo+paclitaxel (Cohorts A,B) \& those with TNBC without PIK3CA/ AKT1/PTEN-altered tumor received ipatasertib+atezolizumab+paclitaxel (Cohort C).
Participant milestones
| Measure |
Cohort A: Placebo + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 milligram per square meter (mg/m\^2), intravenously (IV), on Days 1, 8, and 15 of each 28-day cycle and placebo, orally once a day (QD), on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
87
|
168
|
76
|
146
|
102
|
|
Overall Study
Safety Evaluable Population
|
87
|
166
|
75
|
145
|
102
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
87
|
168
|
76
|
146
|
102
|
Reasons for withdrawal
| Measure |
Cohort A: Placebo + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 milligram per square meter (mg/m\^2), intravenously (IV), on Days 1, 8, and 15 of each 28-day cycle and placebo, orally once a day (QD), on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Overall Study
Reason not Specified
|
12
|
21
|
9
|
9
|
29
|
|
Overall Study
Withdrawal by Subject
|
13
|
15
|
4
|
15
|
6
|
|
Overall Study
Protocol Deviation
|
0
|
1
|
1
|
1
|
0
|
|
Overall Study
Adverse Event
|
1
|
1
|
0
|
1
|
0
|
|
Overall Study
Death
|
40
|
89
|
43
|
76
|
50
|
|
Overall Study
Lost to Follow-up
|
5
|
5
|
4
|
7
|
4
|
|
Overall Study
Physician Decision
|
16
|
34
|
14
|
34
|
13
|
|
Overall Study
Progressive Disease
|
0
|
2
|
1
|
2
|
0
|
|
Overall Study
Symptomatic Deterioration
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer
Baseline characteristics by cohort
| Measure |
Cohort A: Placebo + Paclitaxel
n=87 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=168 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
n=76 Participants
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
n=146 Participants
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
n=102 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
Total
n=579 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
54.2 years
STANDARD_DEVIATION 12.6 • n=5 Participants
|
54.6 years
STANDARD_DEVIATION 12.8 • n=7 Participants
|
54.5 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
57.2 years
STANDARD_DEVIATION 11.1 • n=4 Participants
|
54.6 years
STANDARD_DEVIATION 11.7 • n=21 Participants
|
55.2 years
STANDARD_DEVIATION 12.0 • n=8 Participants
|
|
Sex: Female, Male
Female
|
87 Participants
n=5 Participants
|
167 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
144 Participants
n=4 Participants
|
102 Participants
n=21 Participants
|
576 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
29 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
36 Participants
n=21 Participants
|
166 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
57 Participants
n=5 Participants
|
101 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
115 Participants
n=4 Participants
|
58 Participants
n=21 Participants
|
393 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
20 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
40 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
17 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
38 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
126 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
20 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
51 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
93 Participants
n=4 Participants
|
55 Participants
n=21 Participants
|
343 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
11 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
38 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: From randomization up to 27 monthsPopulation: ITT Population included all randomized participants in Cohorts A regardless of whether the participants received the assigned treatment.
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1), or death from any cause, whichever occurred first, assessed up to 27 months for this outcome measure. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=87 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=168 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort A: Progression-Free Survival (PFS)
|
6.1 months
Interval 5.5 to 9.0
|
7.4 months
Interval 5.6 to 8.5
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From randomization up to 24.4 monthsPopulation: ITT Population included all randomized participants in Cohort B regardless of whether the participants received the assigned treatment.
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 24.4 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Abbreviation used in statistical analysis: PI3K=phosphoinositide 3-kinase and mTOR=mammalian target of rapamycin inhibitor.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=76 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=146 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort B: PFS
|
9.3 months
Interval 7.2 to 12.2
|
9.3 months
Interval 8.0 to 11.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From enrollment up to 31 monthsPopulation: ITT population included of all enrolled participants in Cohort C.
PFS for Cohort C was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=102 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: PFS
|
7.1 months
Interval 5.5 to 9.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort BPopulation: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. Overall number analyzed is the number of participants with measurable disease at baseline.
ORR was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=86 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=167 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
n=75 Participants
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
n=144 Participants
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort A and B: Objective Response Rate (ORR)
|
34.9 percentage of participants
Interval 24.92 to 45.92
|
38.9 percentage of participants
Interval 31.49 to 46.76
|
46.7 percentage of participants
Interval 35.05 to 58.55
|
46.5 percentage of participants
Interval 38.18 to 55.02
|
—
|
SECONDARY outcome
Timeframe: From enrollment up to 31 monthsPopulation: ITT population consisted of all enrolled participants in Cohort C.
ORR was defined as percentage of participants with PR or CR on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=102 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: ORR
|
52.9 percentage of participants
Interval 42.8 to 62.9
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort BPopulation: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. Overall number analyzed is the number of participants with objective response i.e., responders.
DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=30 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=65 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
n=35 Participants
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
n=67 Participants
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort A and B: Duration of Response (DOR)
|
16.6 months
Interval 4.9 to
The upper limit of 95% confidence interval (CI) was not estimable due to insufficient number of participants with event.
|
9.4 months
Interval 7.3 to 11.1
|
9.2 months
Interval 6.8 to 12.5
|
9.2 months
Interval 7.2 to 11.3
|
—
|
SECONDARY outcome
Timeframe: From enrollment up to 31 monthsPopulation: ITT population consisted of all enrolled participants in Cohort C. Overall number analyzed is the number of participants with objective response i.e., responders.
DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=54 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: DOR
|
8.7 months
Interval 5.7 to 12.7
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort BPopulation: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. Overall number analyzed is the number of participants with measurable disease at baseline.
CBR was defined as percentage of participants with an objective response (CR or PR), or stable disease (SD) for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1. assessed up to From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=86 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=167 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
n=75 Participants
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
n=144 Participants
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort A and B: Clinical Benefit Rate (CBR)
|
45.3 percentage of participants
Interval 34.58 to 56.45
|
46.7 percentage of participants
Interval 38.96 to 54.57
|
65.3 percentage of participants
Interval 53.46 to 75.96
|
68.8 percentage of participants
Interval 60.5 to 76.21
|
—
|
SECONDARY outcome
Timeframe: From enrollment up to 31 monthsPopulation: ITT population consisted of all enrolled participants in Cohort C.
CBR was defined as percentage of participants with an objective response (CR or PR), or SD for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1 assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=102 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: CBR
|
54.9 percentage of participants
Interval 44.74 to 64.78
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From randomization/ enrollment (Cohort C) up to death from any cause, up to 45 months for Cohort A, up to 46 months for Cohort B and up to 31 months for Cohort CPopulation: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C.
OS was defined as the time from randomization to death from any cause.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=87 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=168 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
n=76 Participants
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
n=146 Participants
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
n=102 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Overall Survival (OS)
|
24.9 months
Interval 16.9 to 40.4
|
24.2 months
Interval 19.2 to 29.4
|
28.4 months
Interval 20.6 to 37.3
|
29.0 months
Interval 22.4 to 34.8
|
22.8 months
Interval 17.8 to
The upper limit of 95% CI was not estimable due to insufficient number of participants with events.
|
SECONDARY outcome
Timeframe: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 (cycle length=28 days)Population: Patient-reported outcome (PRO)-evaluable Population included all randomized (Cohorts A and B) participants who had a baseline and at least 1 postbaseline PRO assessment.Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=79 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=160 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
n=73 Participants
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
n=146 Participants
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 5
|
-2.08 score on scale
Standard Deviation 16.46
|
-2.87 score on scale
Standard Deviation 18.61
|
-1.19 score on scale
Standard Deviation 20.00
|
-3.01 score on scale
Standard Deviation 18.70
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 9
|
0.00 score on scale
Standard Deviation 10.29
|
-3.49 score on scale
Standard Deviation 25.28
|
1.10 score on scale
Standard Deviation 18.80
|
-7.37 score on scale
Standard Deviation 20.05
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 10
|
-2.38 score on scale
Standard Deviation 9.91
|
-4.52 score on scale
Standard Deviation 21.61
|
1.28 score on scale
Standard Deviation 19.64
|
-6.43 score on scale
Standard Deviation 18.83
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 12
|
0.76 score on scale
Standard Deviation 11.46
|
-8.33 score on scale
Standard Deviation 19.94
|
0.00 score on scale
Standard Deviation 22.46
|
-4.02 score on scale
Standard Deviation 16.32
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 13
|
-5.21 score on scale
Standard Deviation 10.85
|
-8.33 score on scale
Standard Deviation 23.57
|
-2.43 score on scale
Standard Deviation 21.63
|
-4.65 score on scale
Standard Deviation 18.57
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 14
|
-2.38 score on scale
Standard Deviation 10.45
|
-3.57 score on scale
Standard Deviation 19.26
|
-0.76 score on scale
Standard Deviation 21.81
|
-3.29 score on scale
Standard Deviation 15.68
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 18
|
-8.33 score on scale
Standard Deviation 9.62
|
-15.48 score on scale
Standard Deviation 16.96
|
-9.26 score on scale
Standard Deviation 19.74
|
-6.55 score on scale
Standard Deviation 16.07
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 21
|
-16.67 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
-16.67 score on scale
Standard Deviation 0.00
|
-13.89 score on scale
Standard Deviation 20.97
|
-10.71 score on scale
Standard Deviation 13.36
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 2
|
0.95 score on scale
Standard Deviation 20.59
|
-0.26 score on scale
Standard Deviation 24.58
|
4.79 score on scale
Standard Deviation 15.83
|
-3.61 score on scale
Standard Deviation 21.45
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 3
|
-0.93 score on scale
Standard Deviation 20.53
|
0.35 score on scale
Standard Deviation 21.73
|
1.19 score on scale
Standard Deviation 19.62
|
-2.13 score on scale
Standard Deviation 17.99
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 4
|
-4.44 score on scale
Standard Deviation 19.42
|
-2.42 score on scale
Standard Deviation 21.95
|
-0.79 score on scale
Standard Deviation 21.10
|
-1.99 score on scale
Standard Deviation 20.75
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 6
|
-6.94 score on scale
Standard Deviation 15.97
|
-2.06 score on scale
Standard Deviation 21.04
|
1.42 score on scale
Standard Deviation 19.18
|
-3.88 score on scale
Standard Deviation 20.67
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 7
|
-5.48 score on scale
Standard Deviation 12.45
|
-3.28 score on scale
Standard Deviation 20.93
|
0.34 score on scale
Standard Deviation 20.34
|
-4.17 score on scale
Standard Deviation 19.47
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 8
|
-6.90 score on scale
Standard Deviation 13.56
|
0.33 score on scale
Standard Deviation 22.11
|
0.35 score on scale
Standard Deviation 16.84
|
-5.99 score on scale
Standard Deviation 18.55
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 11
|
-3.43 score on scale
Standard Deviation 15.88
|
-4.46 score on scale
Standard Deviation 21.09
|
2.38 score on scale
Standard Deviation 22.83
|
-5.13 score on scale
Standard Deviation 19.30
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 15
|
-9.72 score on scale
Standard Deviation 11.08
|
-5.77 score on scale
Standard Deviation 12.90
|
-2.22 score on scale
Standard Deviation 18.49
|
-0.62 score on scale
Standard Deviation 20.14
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 16
|
-6.67 score on scale
Standard Deviation 13.69
|
-8.33 score on scale
Standard Deviation 14.91
|
-4.17 score on scale
Standard Deviation 19.27
|
-2.33 score on scale
Standard Deviation 16.05
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 17
|
-8.33 score on scale
Standard Deviation 9.62
|
-6.82 score on scale
Standard Deviation 13.34
|
-7.64 score on scale
Standard Deviation 15.27
|
-5.95 score on scale
Standard Deviation 13.73
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 19
|
-4.17 score on scale
Standard Deviation 8.33
|
-20.00 score on scale
Standard Deviation 7.45
|
-11.67 score on scale
Standard Deviation 16.24
|
-7.64 score on scale
Standard Deviation 23.96
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 20
|
-8.33 score on scale
Standard Deviation 11.79
|
-5.56 score on scale
Standard Deviation 9.62
|
-16.67 score on scale
Standard Deviation 11.79
|
-10.00 score on scale
Standard Deviation 12.30
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 22
|
-16.67 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
-16.67 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
-11.11 score on scale
Standard Deviation 9.62
|
-14.29 score on scale
Standard Deviation 15.00
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 23
|
-16.67 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
-25.00 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
-16.67 score on scale
Standard Deviation 16.67
|
-15.00 score on scale
Standard Deviation 18.07
|
—
|
|
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 24
|
-16.67 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
-41.67 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
-16.67 score on scale
Standard Deviation 0.00
|
-16.67 score on scale
Standard Deviation 11.79
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 (cycle length=28 days)Population: PRO-evaluable Population for Cohort C included all enrolled participants who had a baseline and at least 1 postbaseline PRO assessment.Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=100 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 39
|
25.00 score on scale
Standard Deviation 35.36
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 24
|
3.79 score on scale
Standard Deviation 24.54
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 25
|
-4.63 score on scale
Standard Deviation 21.29
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 2
|
-0.42 score on scale
Standard Deviation 18.02
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 3
|
0.18 score on scale
Standard Deviation 18.32
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 4
|
-4.37 score on scale
Standard Deviation 22.83
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 5
|
-6.41 score on scale
Standard Deviation 20.19
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 6
|
-7.10 score on scale
Standard Deviation 21.24
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 7
|
-5.09 score on scale
Standard Deviation 18.20
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 8
|
-4.83 score on scale
Standard Deviation 21.24
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 9
|
-7.66 score on scale
Standard Deviation 23.68
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 10
|
-7.07 score on scale
Standard Deviation 18.76
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 11
|
-6.00 score on scale
Standard Deviation 19.02
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 12
|
-2.90 score on scale
Standard Deviation 18.57
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 13
|
-1.45 score on scale
Standard Deviation 19.08
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 14
|
-7.89 score on scale
Standard Deviation 21.24
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 15
|
-5.09 score on scale
Standard Deviation 26.37
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 16
|
-11.98 score on scale
Standard Deviation 27.55
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 17
|
-10.90 score on scale
Standard Deviation 32.16
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 18
|
-3.85 score on scale
Standard Deviation 20.30
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 19
|
-3.21 score on scale
Standard Deviation 25.35
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 20
|
-3.21 score on scale
Standard Deviation 24.89
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 21
|
-2.56 score on scale
Standard Deviation 24.86
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 22
|
-12.18 score on scale
Standard Deviation 32.92
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 23
|
3.03 score on scale
Standard Deviation 24.23
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 26
|
-0.83 score on scale
Standard Deviation 19.82
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 27
|
2.08 score on scale
Standard Deviation 26.63
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 28
|
1.39 score on scale
Standard Deviation 23.81
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 29
|
-1.19 score on scale
Standard Deviation 28.64
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 30
|
3.33 score on scale
Standard Deviation 24.01
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 31
|
22.22 score on scale
Standard Deviation 12.73
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 32
|
10.42 score on scale
Standard Deviation 23.94
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 33
|
16.67 score on scale
Standard Deviation 22.05
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 34
|
16.67 score on scale
Standard Deviation 30.05
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 35
|
13.89 score on scale
Standard Deviation 17.35
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 36
|
20.83 score on scale
Standard Deviation 29.46
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 37
|
16.67 score on scale
Standard Deviation 23.57
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 38
|
16.67 score on scale
Standard Deviation 23.57
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 40
|
33.33 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 41
|
50.00 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 42
|
41.67 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 43
|
41.67 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
—
|
—
|
—
|
—
|
|
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Day 1 Cycle 44
|
50.00 score on scale
Standard Deviation NA
The standard deviation was not estimable for a single participant.
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 24.4 monthsPopulation: ITT Population for Cohort B included as all randomized participants regardless of whether the participants received the assigned treatment.
Time to deterioration in GHS/HRQoL was defined as the time from randomization to first observed ≥ 11-point increase from Baseline in pain scale score (Question 9 and 19) in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score, assessed up 24.4 months for this outcome measure. TTD was planned to be assessed only in cohort with HR+/HER2 - breast cancer participants (Cohort B). Questions 9 and 19 that assessed pain, used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). The scores were linearly transformed on a scale of 0 to 100, with higher scores indicating increased severity in symptoms.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=76 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=146 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort B: Time to Deterioration (TTD) in Pain
|
NA months
Median and 95% CI were not estimable due to insufficient number of participants with events.
|
NA months
Interval 11.1 to
Median and upper limit of 95% CI were not estimable due to insufficient number of participants with events.
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort CPopulation: Safety Evaluable Population included all participants who received any amount of study treatment.
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=87 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=166 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
n=75 Participants
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
n=145 Participants
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
n=102 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs)
|
84 Participants
|
162 Participants
|
74 Participants
|
144 Participants
|
102 Participants
|
SECONDARY outcome
Timeframe: Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort CPopulation: Safety Evaluable Population included all participants who received any amount of study treatment.
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the NCI CTCAE, Version 4.0. AESI include cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. Suspected transmission of an infectious agent by the study drug, Grade \>= 3 fasting hyperglycemia, hepatotoxicity, diarrhea, rash, ALT/AST elevations. Grade \>= 2 colitis/enterocolitis.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=87 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=166 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
n=75 Participants
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
n=145 Participants
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
n=102 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Number of Participants With at Least One Adverse Events of Special Interest (AESI)
|
79 Participants
|
157 Participants
|
73 Participants
|
141 Participants
|
101 Participants
|
SECONDARY outcome
Timeframe: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)Population: PK Evaluable Population included all participants who had at least one evaluable plasma sample. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=146 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=132 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohorts A and B:Plasma Concentration of Ipatasertib
Cycle 1 Day 1
|
176 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 232
|
165 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 326
|
—
|
—
|
—
|
|
Cohorts A and B:Plasma Concentration of Ipatasertib
Cycle 1 Day 15
|
191 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 184
|
211 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 216
|
—
|
—
|
—
|
|
Cohorts A and B:Plasma Concentration of Ipatasertib
Cycle 3 Day 15
|
165 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 169
|
234 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 149
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)Population: PK Evaluable Population included all participants who had at least one evaluable plasma sample. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=94 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: Plasma Concentration of Ipatasertib
Cycle 1 Day 1
|
175 ng/mL
Geometric Coefficient of Variation 183
|
—
|
—
|
—
|
—
|
|
Cohort C: Plasma Concentration of Ipatasertib
Cycle 1 Day 15
|
233 ng/mL
Geometric Coefficient of Variation 161.6
|
—
|
—
|
—
|
—
|
|
Cohort C: Plasma Concentration of Ipatasertib
Cycle 3 Day 15
|
207 ng/mL
Geometric Coefficient of Variation 197.6
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )Population: PK Evaluable Population included all participants who had at least one evaluable plasma sample. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
G-037720 was a metabolite of ipatasertib.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=146 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
n=123 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohorts A and B: Plasma Concentration of G-037720
Cycle 1 Day 1
|
45.6 ng/mL
Geometric Coefficient of Variation 777
|
68.2 ng/mL
Geometric Coefficient of Variation 405
|
—
|
—
|
—
|
|
Cohorts A and B: Plasma Concentration of G-037720
Cycle 1 Day 15
|
83.9 ng/mL
Geometric Coefficient of Variation 183
|
95.1 ng/mL
Geometric Coefficient of Variation 211
|
—
|
—
|
—
|
|
Cohorts A and B: Plasma Concentration of G-037720
Cycle 3 Day 15
|
90.8 ng/mL
Geometric Coefficient of Variation 180
|
109 ng/mL
Geometric Coefficient of Variation 169
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )Population: PK Evaluable Population included all participants who had at least one evaluable plasma sample. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
G-037720 was a metabolite of ipatasertib.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=91 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: Plasma Concentration of G-037720
Cycle 1 Day 1
|
67.3 ng/mL
Geometric Coefficient of Variation 222.3
|
—
|
—
|
—
|
—
|
|
Cohort C: Plasma Concentration of G-037720
Cycle 1 Day 15
|
96.8 ng/mL
Geometric Coefficient of Variation 140.7
|
—
|
—
|
—
|
—
|
|
Cohort C: Plasma Concentration of G-037720
Cycle 3 Day 15
|
96.5 ng/mL
Geometric Coefficient of Variation 167.9
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From enrollment until the occurrence of disease progression or death from any cause, whichever occurred earlier, up to 1 yearPopulation: ITT Population for Cohort C included all enrolled participants in Cohort C.
PFS was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first. Event-free PFS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Percentages are rounded off to the nearest decimal point. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=102 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: 1-year Event-free PFS Rate
|
31.17 percentage of participants
Interval 21.59 to 40.76
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From enrollment up to death from any cause, up to 1 yearPopulation: ITT Population for Cohort C included all enrolled participants in Cohort C.
OS was defined as the time from enrollment to death from any cause. Event-free OS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. As prespecified in the protocol, this outcome measure was applicable only to Cohort C. Percentages were rounded off to the nearest decimal.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=102 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: 1-year Event-free OS Rate
|
79.38 percentage of participants
Interval 71.31 to 87.44
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of Cycle 1: 30 minutes post dose, predose on Day 15 of Cycle 1 and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length=28 days)Population: For Cohort C, PK Evaluable Population included all participants who had at least one evaluable plasma sample in Cohort C. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=101 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: Serum Concentration of Atezolizumab
Day 1 Cycle 1
|
309 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 31.7
|
—
|
—
|
—
|
—
|
|
Cohort C: Serum Concentration of Atezolizumab
Day 15 Cycle 1
|
91.5 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 23.9
|
—
|
—
|
—
|
—
|
|
Cohort C: Serum Concentration of Atezolizumab
Day 1 Cycle 2
|
130 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 54.1
|
—
|
—
|
—
|
—
|
|
Cohort C: Serum Concentration of Atezolizumab
Day 1 Cycle 3
|
200 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 41.1
|
—
|
—
|
—
|
—
|
|
Cohort C: Serum Concentration of Atezolizumab
Day 1 Cycle 4
|
231 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 52.3
|
—
|
—
|
—
|
—
|
|
Cohort C: Serum Concentration of Atezolizumab
Day 1 Cycle 8
|
327 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 27.6
|
—
|
—
|
—
|
—
|
|
Cohort C: Serum Concentration of Atezolizumab
Day 1 Cycle 12
|
371 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 30.5
|
—
|
—
|
—
|
—
|
|
Cohort C: Serum Concentration of Atezolizumab
Day 1 Cycle 16
|
402 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 42.4
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 45.5 monthsPopulation: For Cohort C, Safety Evaluable Population included all participants who received any amount of study treatment in cohort C. Overall number analyzed is the number of participants with an ADA assay result from at least one post-baseline sample.
The numbers of ADA-positive participants after drug administration were summarized for participants exposed to atezolizumab. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Outcome measures
| Measure |
Cohort A: Placebo + Paclitaxel
n=101 Participants
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort A: Ipatasertib + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
Cohort B: Placebo + Paclitaxel
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort B: Ipatasertib + Paclitaxel
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Cohort C: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
|
18 Participants
|
—
|
—
|
—
|
—
|
Adverse Events
COHORT A Placebo + Paclitaxel
Serious events: 20 serious events
Other events: 82 other events
Deaths: 41 deaths
COHORT A Ipatasertib + Paclitaxel
Serious events: 34 serious events
Other events: 161 other events
Deaths: 91 deaths
COHORT B Placebo + Paclitaxel
Serious events: 11 serious events
Other events: 72 other events
Deaths: 44 deaths
COHORT B Ipatasertib + Paclitaxel
Serious events: 30 serious events
Other events: 141 other events
Deaths: 78 deaths
COHORT C Ipatasertib + Atezolizumab + Paclitaxel
Serious events: 29 serious events
Other events: 101 other events
Deaths: 50 deaths
Serious adverse events
| Measure |
COHORT A Placebo + Paclitaxel
n=87 participants at risk
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
COHORT A Ipatasertib + Paclitaxel
n=166 participants at risk
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
COHORT B Placebo + Paclitaxel
n=75 participants at risk
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
COHORT B Ipatasertib + Paclitaxel
n=145 participants at risk
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
COHORT C Ipatasertib + Atezolizumab + Paclitaxel
n=102 participants at risk
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.8%
3/166 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.4%
2/145 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.4%
2/145 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Cardiac disorders
Myocarditis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Cardiac disorders
Sinus tachycardia
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Eye disorders
Epiretinal membrane
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Eye disorders
Glaucoma
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Eye disorders
Macular oedema
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Chronic gastritis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Colitis
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.6%
6/166 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.8%
4/145 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.9%
4/102 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.2%
2/166 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.2%
2/166 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Death
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Extravasation
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Fatigue
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
General physical health deterioration
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Hyperthermia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Pyrexia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.9%
4/102 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Hepatobiliary disorders
Autoimmune hepatitis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Abdominal abscess
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Abscess jaw
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
COVID-19
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
COVID-19 pneumonia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Cellulitis
|
1.1%
1/87 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Emphysematous cystitis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Erysipelas
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Gastroenteritis norovirus
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Influenza
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Peritonitis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Pneumonia
|
4.6%
4/87 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.2%
2/166 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.4%
2/145 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.9%
3/102 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Sepsis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Skin infection
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Suspected COVID-19
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.9%
3/102 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Viral infection
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Wound infection
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc compression
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm
|
1.1%
1/87 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangiosis carcinomatosa
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Schwannoma
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour fistulisation
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour necrosis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Dystonia
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Immune-mediated lung disease
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.3%
2/87 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.4%
2/145 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.8%
3/166 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.60%
1/166 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.69%
1/145 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/102 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
Other adverse events
| Measure |
COHORT A Placebo + Paclitaxel
n=87 participants at risk
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
COHORT A Ipatasertib + Paclitaxel
n=166 participants at risk
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
|
COHORT B Placebo + Paclitaxel
n=75 participants at risk
Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
COHORT B Ipatasertib + Paclitaxel
n=145 participants at risk
Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
|
COHORT C Ipatasertib + Atezolizumab + Paclitaxel
n=102 participants at risk
Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting received paclitaxel chemotherapy 80 mg/m\^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
|
|---|---|---|---|---|---|
|
Vascular disorders
Hypertension
|
3.4%
3/87 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.6%
6/166 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.5%
8/145 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.8%
8/102 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.2%
7/166 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.7%
5/75 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.1%
6/145 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Blood and lymphatic system disorders
Anaemia
|
26.4%
23/87 • Number of events 34 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
25.9%
43/166 • Number of events 58 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
20.0%
15/75 • Number of events 28 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
31.0%
45/145 • Number of events 57 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
33.3%
34/102 • Number of events 50 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Blood and lymphatic system disorders
Leukopenia
|
4.6%
4/87 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.2%
7/166 • Number of events 23 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.3%
7/75 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.5%
8/145 • Number of events 18 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.8%
11/102 • Number of events 49 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Blood and lymphatic system disorders
Neutropenia
|
23.0%
20/87 • Number of events 39 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
16.9%
28/166 • Number of events 92 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
24.0%
18/75 • Number of events 58 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
24.8%
36/145 • Number of events 95 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
24.5%
25/102 • Number of events 114 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Ear and labyrinth disorders
Vertigo
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.4%
9/166 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.7%
2/75 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.8%
4/145 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.9%
6/102 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
5.7%
5/87 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.0%
15/166 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.3%
7/75 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.6%
11/145 • Number of events 17 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
11.8%
12/102 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.2%
8/87 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.6%
16/166 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.7%
5/75 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.3%
15/145 • Number of events 21 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.9%
6/102 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Constipation
|
35.6%
31/87 • Number of events 40 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
29.5%
49/166 • Number of events 56 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
34.7%
26/75 • Number of events 33 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
29.0%
42/145 • Number of events 54 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
12.7%
13/102 • Number of events 20 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
32.2%
28/87 • Number of events 56 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
83.1%
138/166 • Number of events 477 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
38.7%
29/75 • Number of events 64 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
86.2%
125/145 • Number of events 461 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
84.3%
86/102 • Number of events 324 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Dyspepsia
|
4.6%
4/87 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.4%
14/166 • Number of events 18 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.2%
9/145 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.9%
6/102 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Flatulence
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.0%
5/166 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.8%
7/145 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.9%
3/102 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.4%
4/166 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.8%
4/145 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.9%
5/102 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Nausea
|
25.3%
22/87 • Number of events 29 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
39.8%
66/166 • Number of events 106 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
22.7%
17/75 • Number of events 28 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
41.4%
60/145 • Number of events 94 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
41.2%
42/102 • Number of events 65 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Stomatitis
|
6.9%
6/87 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.8%
18/166 • Number of events 31 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.0%
6/75 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
11.0%
16/145 • Number of events 27 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.9%
7/102 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
9.2%
8/87 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
31.9%
53/166 • Number of events 112 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.0%
6/75 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
31.0%
45/145 • Number of events 67 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
27.5%
28/102 • Number of events 43 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Asthenia
|
11.5%
10/87 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
21.1%
35/166 • Number of events 40 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
17.3%
13/75 • Number of events 17 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
18.6%
27/145 • Number of events 36 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
18.6%
19/102 • Number of events 22 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Fatigue
|
17.2%
15/87 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
18.1%
30/166 • Number of events 33 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
25.3%
19/75 • Number of events 30 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
20.0%
29/145 • Number of events 36 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
22.5%
23/102 • Number of events 35 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Mucosal inflammation
|
2.3%
2/87 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.6%
11/166 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.0%
3/75 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.5%
8/145 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
11.8%
12/102 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Oedema
|
2.3%
2/87 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.0%
5/166 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.2%
9/145 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.9%
3/102 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Oedema peripheral
|
8.0%
7/87 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.8%
18/166 • Number of events 23 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
18.7%
14/75 • Number of events 19 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
14.5%
21/145 • Number of events 28 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.9%
7/102 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
General disorders
Pyrexia
|
6.9%
6/87 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.6%
16/166 • Number of events 17 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
15.9%
23/145 • Number of events 30 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.8%
9/102 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
3.4%
3/87 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 38 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.1%
6/145 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.9%
6/102 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Immune system disorders
Hypersensitivity
|
5.7%
5/87 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.4%
4/166 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Cystitis
|
3.4%
3/87 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.8%
8/166 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.0%
6/75 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.8%
7/145 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Nasopharyngitis
|
3.4%
3/87 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.6%
11/166 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.3%
7/75 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
13.1%
19/145 • Number of events 24 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.9%
5/102 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
3.4%
3/87 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.2%
12/166 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.0%
6/75 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.7%
14/145 • Number of events 19 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.8%
8/102 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Infections and infestations
Urinary tract infection
|
2.3%
2/87 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.2%
12/166 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
11.0%
16/145 • Number of events 18 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.9%
7/102 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
3.4%
3/87 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.6%
6/166 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.3%
1/75 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.1%
6/145 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.9%
6/102 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Alanine aminotransferase increased
|
8.0%
7/87 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
13.9%
23/166 • Number of events 29 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
20.0%
15/75 • Number of events 30 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
13.1%
19/145 • Number of events 27 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
24.5%
25/102 • Number of events 59 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Aspartate aminotransferase increased
|
6.9%
6/87 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.8%
18/166 • Number of events 23 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
13.3%
10/75 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.0%
13/145 • Number of events 18 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
20.6%
21/102 • Number of events 39 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Blood alkaline phosphatase increased
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.4%
9/166 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.3%
7/75 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.1%
3/145 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
11.8%
12/102 • Number of events 20 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Blood lactate dehydrogenase increased
|
4.6%
4/87 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.2%
7/166 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.7%
8/75 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.4%
5/145 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.9%
7/102 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Neutrophil count decreased
|
11.5%
10/87 • Number of events 23 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
13.3%
22/166 • Number of events 49 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
24.0%
18/75 • Number of events 65 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
15.9%
23/145 • Number of events 94 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.8%
8/102 • Number of events 33 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Weight decreased
|
3.4%
3/87 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.2%
12/166 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.7%
2/75 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.8%
7/145 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.9%
7/102 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
Weight increased
|
1.1%
1/87 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.8%
3/166 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.0%
3/75 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/145 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.9%
6/102 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Investigations
White blood cell count decreased
|
8.0%
7/87 • Number of events 15 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.6%
11/166 • Number of events 28 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.7%
5/75 • Number of events 27 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.9%
10/145 • Number of events 44 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.9%
5/102 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.5%
10/87 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
17.5%
29/166 • Number of events 35 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.3%
7/75 • Number of events 15 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
14.5%
21/145 • Number of events 29 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
13.7%
14/102 • Number of events 15 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.3%
9/87 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
18.7%
31/166 • Number of events 49 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
13.3%
10/75 • Number of events 39 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
13.1%
19/145 • Number of events 27 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
21.6%
22/102 • Number of events 42 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
2.3%
2/87 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.4%
9/166 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.7%
5/75 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.8%
7/145 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.9%
4/102 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
3.4%
3/87 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.0%
5/166 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.7%
2/75 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.1%
6/145 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.8%
8/102 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.8%
12/87 • Number of events 18 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.6%
16/166 • Number of events 24 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
13.3%
10/75 • Number of events 16 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
17.9%
26/145 • Number of events 40 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
12.7%
13/102 • Number of events 19 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.3%
9/87 • Number of events 14 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.6%
16/166 • Number of events 21 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.3%
7/75 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
14.5%
21/145 • Number of events 25 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.8%
10/102 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.2%
7/166 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.2%
9/145 • Number of events 17 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.0%
2/102 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
1.1%
1/87 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.4%
4/166 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.7%
5/75 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.1%
3/145 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.9%
5/102 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.7%
5/87 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.6%
16/166 • Number of events 24 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
12.0%
9/75 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.3%
15/145 • Number of events 17 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.8%
10/102 • Number of events 14 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.6%
4/87 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.4%
14/166 • Number of events 18 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.0%
6/75 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.0%
13/145 • Number of events 24 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.9%
4/102 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Dizziness
|
9.2%
8/87 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.6%
6/166 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.0%
3/75 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.9%
10/145 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.8%
10/102 • Number of events 14 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Dysgeusia
|
9.2%
8/87 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.0%
10/166 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.6%
11/145 • Number of events 12 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.9%
6/102 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Headache
|
11.5%
10/87 • Number of events 19 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
16.9%
28/166 • Number of events 56 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.7%
8/75 • Number of events 19 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
16.6%
24/145 • Number of events 37 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
20.6%
21/102 • Number of events 33 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Neuropathy peripheral
|
23.0%
20/87 • Number of events 23 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
23.5%
39/166 • Number of events 49 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
16.0%
12/75 • Number of events 15 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
31.7%
46/145 • Number of events 63 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
29.4%
30/102 • Number of events 41 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Paraesthesia
|
2.3%
2/87 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.8%
8/166 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.0%
6/75 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.0%
13/145 • Number of events 14 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.9%
5/102 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
21.8%
19/87 • Number of events 19 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
19.3%
32/166 • Number of events 38 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
30.7%
23/75 • Number of events 24 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
15.9%
23/145 • Number of events 30 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.8%
8/102 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Nervous system disorders
Polyneuropathy
|
8.0%
7/87 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.0%
5/166 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.0%
6/75 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.3%
12/145 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.8%
8/102 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Psychiatric disorders
Insomnia
|
5.7%
5/87 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.0%
10/166 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.0%
6/75 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.1%
6/145 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.8%
10/102 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Reproductive system and breast disorders
Breast pain
|
3.4%
3/87 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.4%
9/166 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/75 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.1%
3/145 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.9%
4/102 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.5%
10/87 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.4%
14/166 • Number of events 15 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.0%
6/75 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
15.9%
23/145 • Number of events 32 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
15.7%
16/102 • Number of events 18 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.0%
7/87 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.2%
7/166 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.7%
2/75 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.9%
10/145 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
8.8%
9/102 • Number of events 11 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.4%
3/87 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.2%
12/166 • Number of events 14 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.3%
15/145 • Number of events 17 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.8%
8/102 • Number of events 10 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.8%
13/166 • Number of events 18 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.7%
2/75 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.6%
11/145 • Number of events 15 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.9%
6/102 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
43.7%
38/87 • Number of events 39 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
47.0%
78/166 • Number of events 80 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
58.7%
44/75 • Number of events 46 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
51.7%
75/145 • Number of events 79 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
41.2%
42/102 • Number of events 42 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.6%
4/87 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.00%
0/166 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.7%
5/75 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.4%
5/145 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.7%
5/87 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.8%
3/166 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.0%
3/75 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.4%
5/145 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.9%
3/102 • Number of events 3 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
4.6%
4/87 • Number of events 4 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.6%
6/166 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.7%
8/75 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
6.2%
9/145 • Number of events 9 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
0.98%
1/102 • Number of events 1 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.0%
7/87 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
9.0%
15/166 • Number of events 21 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.0%
3/75 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
10.3%
15/145 • Number of events 25 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
16.7%
17/102 • Number of events 24 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.6%
11/87 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
15.7%
26/166 • Number of events 37 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
12.0%
9/75 • Number of events 13 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
21.4%
31/145 • Number of events 55 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
28.4%
29/102 • Number of events 40 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/87 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
3.0%
5/166 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
5.3%
4/75 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.8%
7/145 • Number of events 7 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
4.9%
5/102 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
|
Vascular disorders
Flushing
|
1.1%
1/87 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
1.8%
3/166 • Number of events 6 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.7%
2/75 • Number of events 2 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
2.8%
4/145 • Number of events 5 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
7.8%
8/102 • Number of events 8 • Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
|
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