Trial Outcomes & Findings for A Phase 2 Study of Intravenous or Subcutaneous Dosing of Sotatercept (ACE-011) in Patients With End-Stage Kidney Disease on Hemodialysis (NCT NCT01999582)
NCT ID: NCT01999582
Last Updated: 2024-06-24
Results Overview
Area Under the plasma concentration-time curve over 14-day dosing interval (AUC14) for Sotatercept., The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
50 participants
Primary outcome timeframe
Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dose
Results posted on
2024-06-24
Participant Flow
Participant milestones
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
7
|
7
|
9
|
9
|
12
|
6
|
|
Overall Study
COMPLETED
|
4
|
4
|
3
|
6
|
10
|
3
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
6
|
3
|
2
|
3
|
Reasons for withdrawal
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
3
|
0
|
1
|
0
|
|
Overall Study
Other Reasons
|
1
|
0
|
3
|
1
|
1
|
2
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
3
|
0
|
1
|
0
|
0
|
Baseline Characteristics
A Phase 2 Study of Intravenous or Subcutaneous Dosing of Sotatercept (ACE-011) in Patients With End-Stage Kidney Disease on Hemodialysis
Baseline characteristics by cohort
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=7 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=7 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=9 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=9 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=12 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=6 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
59.1 years
STANDARD_DEVIATION 15.43 • n=99 Participants
|
62.3 years
STANDARD_DEVIATION 13.03 • n=107 Participants
|
59.4 years
STANDARD_DEVIATION 15.8 • n=206 Participants
|
61.9 years
STANDARD_DEVIATION 15.43 • n=7 Participants
|
61.4 years
STANDARD_DEVIATION 15.68 • n=31 Participants
|
53.7 years
STANDARD_DEVIATION 15.93 • n=30 Participants
|
60.0 years
STANDARD_DEVIATION 14.75 • n=3 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=31 Participants
|
3 Participants
n=30 Participants
|
22 Participants
n=3 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=31 Participants
|
3 Participants
n=30 Participants
|
28 Participants
n=3 Participants
|
|
Race
White
|
4 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
11 Participants
n=31 Participants
|
6 Participants
n=30 Participants
|
40 Participants
n=3 Participants
|
|
Race
Black or African- American
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
4 Participants
n=3 Participants
|
|
Race
Asian
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
5 Participants
n=3 Participants
|
|
Race
American Indian/Alaska Native
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
1 Participants
n=3 Participants
|
|
Ethnicity
Hispanic or Latino
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
2 Participants
n=3 Participants
|
|
Ethnicity
Not Hispanic or Latino
|
7 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
12 Participants
n=31 Participants
|
6 Participants
n=30 Participants
|
48 Participants
n=3 Participants
|
PRIMARY outcome
Timeframe: Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dosePopulation: Pharmacokinetic population-all treated participants with at least one non-missing plasma concentration data for this endpoint
Area Under the plasma concentration-time curve over 14-day dosing interval (AUC14) for Sotatercept., The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=4 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=3 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=7 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=6 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=7 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=5 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Area Under the Serum Concentration-Time Curve Over Dosing Interval (AUC14d) (14 Days)
|
15204.31 day*ng/mL
Standard Deviation 7096.55 • Interval 7096.55 to
|
11269.14 day*ng/mL
Standard Deviation 1839.92 • Interval 1839.92 to
|
28647.03 day*ng/mL
Standard Deviation 10332.19 • Interval 10332.19 to
|
10327.98 day*ng/mL
Standard Deviation 8065.12 • Interval 8065.12 to
|
15886.83 day*ng/mL
Standard Deviation 4212.12 • Interval 4212.12 to
|
21982.9 day*ng/mL
Standard Deviation 5125.4 • Interval 5125.4 to
|
PRIMARY outcome
Timeframe: Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dosePopulation: Pharmacokinetic population-all treated participants with at least one non-missing plasma concentration data for this endpoint
Area under the plasma concentration-time curve over 28-day dosing interval (AUC28d). All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=4 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=3 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=3 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=4 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=5 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=2 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Area Under the Serum Concentration- Time Curve Over From Day 1 to Day 28 (AUC28d)
|
38361.5 day*ng/mL
Standard Deviation 8589.34 • Interval 8589.34 to
|
41500.36 day*ng/mL
Standard Deviation 13647.28 • Interval 13647.28 to
|
94106.54 day*ng/mL
Standard Deviation 37204.17 • Interval 37204.17 to
|
36065.09 day*ng/mL
Standard Deviation 22817 • Interval 22817.0 to
|
33173.4 day*ng/mL
Standard Deviation 8709.16 • Interval 8709.16 to
|
60497.8 day*ng/mL
Standard Deviation 14623.13 • Interval 14623.13 to
|
PRIMARY outcome
Timeframe: Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dosePopulation: Pharmacokinetic population-all treated participants with at least one non-missing plasma concentration data for this endpoint
Maximum observed serum concentration (Cmax14d) of sotatercept, obtained directly from the observed concentration-time data. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=4 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=3 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=8 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=6 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=7 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=5 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Maximum Observed Serum Concentration Obtained From the First Dose (Cmax14d)
|
2567.6 ng/mL
Standard Deviation 1093.73 • Interval 1093.73 to
|
1024.27 ng/mL
Standard Deviation 145.8 • Interval 145.8 to
|
4623.61 ng/mL
Standard Deviation 1620.66 • Interval 1620.66 to
|
963.05 ng/mL
Standard Deviation 659.65 • Interval 659.65 to
|
3155.53 ng/mL
Standard Deviation 1861.07 • Interval 1861.07 to
|
1993.58 ng/mL
Standard Deviation 375.54 • Interval 375.54 to
|
PRIMARY outcome
Timeframe: Doses 1-2: predose and postdose at 5 min (IV only) 4 hours, 3, and 7 days after each dose; Doses 3-7: predose, and postdose at 5 min after IV injection after each dose; Final dose: predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14 days after dosePopulation: Pharmacokinetic population-all treated participants with at least one non-missing plasma concentration data for this endpoint
Maximum observed serum concentration (Cmax28d) of sotatercept, obtained directly from the observed concentration-time data combining the profiles following the first two doses. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=4 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=3 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=3 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=4 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=5 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=2 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Maximum Observed Serum Concentration (Cmax28d) Obtained From the Combined First 2 Doses
|
3557.93 ng/mL
Standard Deviation 699.19 • Interval 699.19 to
|
3868.83 ng/mL
Standard Deviation 3614.89 • Interval 3614.89 to
|
8613.67 ng/mL
Standard Deviation 3559.69 • Interval 3559.69 to
|
1967.55 ng/mL
Standard Deviation 1128.69 • Interval 1128.69 to
|
3501.54 ng/mL
Standard Deviation 2144.15 • Interval 2144.15 to
|
3161.6 ng/mL
Standard Deviation 788.14 • Interval 788.14 to
|
PRIMARY outcome
Timeframe: Doses 1-2: pre- and postdose at 5 min (IV only) 4 hrs, 3, and 7 days after each dose; Doses 3-7: pre-, and postdose at 5 min after IV injection after each dose; Final dose: pre- and postdose at 5 min (IV only), 4 hrs, 3, 7, 14, 28, 56, 84, and 112 daysPopulation: Pharmacokinetic population-all treated participants with at least one non-missing plasma concentration data for this endpoint
Time to maximum serum concentration (Tmax) of sotatercept, obtained directly from the observed concentration-time data. The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=4 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=3 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=3 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=4 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=5 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=2 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Serum Concentration (Tmax)
|
14.09 days
Full Range 14.01 • Interval 14.01 to 16.0
|
21.01 days
Full Range 16.16 • Interval 16.16 to 27.98
|
14.02 days
Full Range 13.99 • Interval 13.99 to 16.01
|
18.51 days
Full Range 15.99 • Interval 15.99 to 21.02
|
0.1688 days
Full Range 0.0035 • Interval 0.0035 to 15.99
|
21.06 days
Full Range 20.99 • Interval 20.99 to 21.13
|
PRIMARY outcome
Timeframe: Predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14, 28, 56, 84, and 112 days after the final dose.Population: Pharmacokinetic population-all treated participants with at least one non-missing plasma concentration data for this endpoint
Terminal elimination half-life (T1/2). The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analyses of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=6 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=4 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=6 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=8 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=9 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=4 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Estimate of Terminal Elimination Half-Life in Serum at Final Dose Only (t1/2)
|
17.6 days
Standard Deviation 4.631 • Interval 4.631 to
|
25.87 days
Standard Deviation 7.127 • Interval 7.127 to
|
21.76 days
Standard Deviation 3.941 • Interval 3.941 to
|
21.03 days
Standard Deviation 5.4 • Interval 5.4 to
|
22.46 days
Standard Deviation 5.342 • Interval 5.342 to
|
20.39 days
Standard Deviation 5.3 • Interval 5.3 to
|
PRIMARY outcome
Timeframe: Predose and postdose at 5 min (IV only) 4 hours, 3, 7, 14, 28, 56, 84, and 112 days after the final dosePopulation: Pharmacokinetic population-all treated participants with at least one non-missing plasma concentration data for this endpoint
Lambda, apparent terminal rate constant (final dose only). The PK population included all participants in the safety population with at least one non-missing plasma concentration data. All analysis of PK data were based on the PK population and participants were analyzed according to the treatment group to which they were randomized.
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=6 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=4 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=6 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=8 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=4 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=4 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Lambda (ʎz): Apparent Terminal Rate Constant (at Final Dose Only)
|
0.0414 1/day
Standard Deviation 0.0094 • Interval 0.0094 to
|
0.0282 1/day
Standard Deviation 0.0071 • Interval 0.0071 to
|
0.0328 1/day
Standard Deviation 0.0063 • Interval 0.0063 to
|
0.0346 1/day
Standard Deviation 0.0078 • Interval 0.0078 to
|
0.0326 1/day
Standard Deviation 0.0085 • Interval 0.0085 to
|
0.0355 1/day
Standard Deviation 0.0077 • Interval 0.0077 to
|
SECONDARY outcome
Timeframe: Visit 14 to Visit 17 (days 99 to 113)Population: All randomized participants
The percentage of participants able to maintain a mean (Visit 14 to 17) hemoglobin concentration ≥ 100 g/L to ≤ 120 g/L without the need for rescue medication at each dose level. Mean hemoglobin value is a mean of hemoglobin concentrations from Visit 14 to Visit 17 (days 99 to 113).
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=7 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=7 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=9 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=9 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=12 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=6 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Percentage of Participants With Mean Hemoglobin ≥ 100 g/L to ≤ 120 g/L Without Rescue Medication
|
42.9 Percentage of participants
|
42.9 Percentage of participants
|
11.1 Percentage of participants
|
33.3 Percentage of participants
|
25 Percentage of participants
|
50 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Visit 14 to Visit 17 (days 99 to 113)Population: All randomized participants who received at least one dose of treatment.
Change in mean hemoglobin concentration between baseline and Visit 14 to 17 at each dose level. Baseline hemoglobin value is the mean of three consecutive hemoglobin concentrations with the last hemoglobin concentration done within the 7 days prior to randomization and the value obtained on the day of randomization. Visit 14 to 17 hemoglobin value is a mean of hemoglobin concentrations from Day 99 \[Visit 14\] to Day 113 \[Visit 17\].
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=7 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=5 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=5 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=7 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=9 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=4 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Mean Hemoglobin Concentration for Visit 14 to 17 (All Participants Regardless of Rescue)
|
-6.9 g/L
Standard Deviation 11.61 • Interval 11.61 to
|
-2.7 g/L
Standard Deviation 6.47 • Interval 6.47 to
|
-2.1 g/L
Standard Deviation 12.23 • Interval 12.23 to
|
-0.8 g/L
Standard Deviation 10.03 • Interval 10.03 to
|
-9.9 g/L
Standard Deviation 9.3 • Interval 9.3 to
|
-6.4 g/L
Standard Deviation 12.6 • Interval 12.6 to
|
SECONDARY outcome
Timeframe: Baseline and Visit 14 to Visit 17 (days 99 to 113)Population: All randomized participants who received at least one dose of treatment and were not rescued prior to Day 115.
Change in mean hemoglobin concentration between baseline and Visit 14 to 17 at each dose level for participants not rescued prior to Day 115. Baseline hemoglobin value is the mean of three consecutive hemoglobin concentrations with the last hemoglobin concentration done within the 7 days prior to randomization and the value obtained on the day of randomization. Visit 14 to 17 hemoglobin value is a mean of hemoglobin concentrations from Day 99 \[Visit 14\] to Day 113 \[Visit 17\].
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=3 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=4 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=2 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=6 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=6 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=3 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Mean Hemoglobin Concentration for Visit 14 to 17 (Participants Not Rescued Prior to Day 115)
|
-7 g/L
Standard Deviation 6.24 • Interval 6.24 to
|
-3.6 g/L
Standard Deviation 7.08 • Interval 7.08 to
|
-0.3 g/L
Standard Deviation 15.2 • Interval 15.2 to
|
0.5 g/L
Standard Deviation 10.28 • Interval 10.28 to
|
-13 g/L
Standard Deviation 10.07 • Interval 10.07 to
|
-1 g/L
Standard Deviation 8.05 • Interval 8.05 to
|
SECONDARY outcome
Timeframe: From date of first dose of investigational product to 112 days after the last dose or until the last study visit, whichever period was longer. The maximum duration for any IV or SC dose was 114 days. Up to approximately 226 days.Population: All randomized participants
Treatment-emergent adverse event (TEAE) was defined as an adverse event with start date on or after date of first dose of study drug. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participants during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. A serious adverse event is defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. Severity and intensity was assessed using the following grading scale: Mild, Moderate and Severe (could be non-serious or serious).
Outcome measures
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=7 Participants
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=7 Participants
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=9 Participants
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=9 Participants
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=12 Participants
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=6 Participants
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Any TEAE
|
7 Participants
|
3 Participants
|
9 Participants
|
6 Participants
|
10 Participants
|
6 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any Treatment-Related TEAE
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any Serious TEAE
|
3 Participants
|
0 Participants
|
3 Participants
|
1 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any Treatment-Related Serious TEAE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any TEAE leading to study drug discontinuation
|
0 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any Severe TEAE
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any TEAE Leading to Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
Adverse Events
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Group 2: Sotatercept 0.2 mg/kg IV Injection
Serious events: 3 serious events
Other events: 9 other events
Deaths: 0 deaths
Group 2: Sotatercept 0.26 mg/kg SC Injection
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
Serious events: 3 serious events
Other events: 9 other events
Deaths: 0 deaths
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
Serious events: 3 serious events
Other events: 6 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=7 participants at risk
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=7 participants at risk
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=9 participants at risk
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=9 participants at risk
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=12 participants at risk
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=6 participants at risk
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Cardiac disorders
Mitral valve incompetence
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Chronic gastritis
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Gastrointestinal angiodysplasia haemorrhagic
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Conjunctivitis
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Device related infection
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Paronychia
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Arteriovenous graft site stenosis
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Shunt thrombosis
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Vascular access malfunction
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Reproductive system and breast disorders
Balanoposthitis
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Vascular disorders
Aortic aneurysm
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
Other adverse events
| Measure |
Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection
n=7 participants at risk
Participants received sotatercept at 0.1 mg/kg administered IV every 14 days for up to 8 doses to evaluate the Pharmacokinetic (PK) and safety of IV versus subcutaneous (SQ) dosing of sotatercept.
|
Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection
n=7 participants at risk
Participants received sotatercept at 0.13 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.2 mg/kg IV Injection
n=9 participants at risk
Participants received sotatercept at 0.2 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 2: Sotatercept 0.26 mg/kg SC Injection
n=9 participants at risk
Participants received sotatercept at 0.26 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.1 - 0.4 mg/kg IV Injection
n=12 participants at risk
Participants received sotatercept at a starting dose of 0.1 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.4 mg/kg administered IV every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
Group 3: Sotatercept 0.4 - 0.5 mg/kg SC Injection
n=6 participants at risk
Participants received sotatercept at 0.4 mg/kg. Intra subject dose escalation will be implemented in response to subjects' individual hemoglobin levels and can be increased in 0.1 mg/kg increments up to 0.5 mg/kg administered SC every 14 days for up to 8 doses to evaluate the PK and safety of IV versus SC dosing of sotatercept.
|
|---|---|---|---|---|---|---|
|
General disorders
Pyrexia
|
14.3%
1/7 • Number of events 4 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Cardiac disorders
Angina pectoris
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Cardiac disorders
Atrial fibrillation
|
14.3%
1/7 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Endocrine disorders
Hyperparathyroidism
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Endocrine disorders
Hyperparathyroidism secondary
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Eye disorders
Amaurosis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Eye disorders
Amaurosis fugax
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Eye disorders
Choroidal effusion
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Chronic gastritis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
14.3%
1/7 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Intra-abdominal haematoma
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
33.3%
2/6 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
33.3%
2/6 • Number of events 5 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
General disorders
Catheter site pain
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
General disorders
Face oedema
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
General disorders
Fatigue
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
General disorders
Malaise
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
General disorders
Oedema peripheral
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Influenza
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
33.3%
2/6 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Localised infection
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Nasopharyngitis
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Infections and infestations
Urinary tract infection
|
28.6%
2/7 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site complication
|
28.6%
2/7 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
28.6%
2/7 • Number of events 3 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 3 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site haematoma
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site haemorrhage
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Foreign body
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Haemodialysis-induced symptom
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Procedural hypotension
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Injury, poisoning and procedural complications
Wound secretion
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Investigations
Cardioactive drug level increased
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Metabolism and nutrition disorders
Calciphylaxis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Metabolism and nutrition disorders
Folate deficiency
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Metabolism and nutrition disorders
Vitamin B12 deficiency
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
33.3%
3/9 • Number of events 3 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
33.3%
2/6 • Number of events 6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Juvenile melanoma benign
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Nervous system disorders
Diabetic neuropathy
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Nervous system disorders
Headache
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
50.0%
3/6 • Number of events 3 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Psychiatric disorders
Depression
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Renal and urinary disorders
Haematuria
|
28.6%
2/7 • Number of events 4 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Renal and urinary disorders
Renal cyst
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Reproductive system and breast disorders
Postmenopausal haemorrhage
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
14.3%
1/7 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
22.2%
2/9 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal obstruction
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
8.3%
1/12 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory acidosis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
1/6 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Vascular disorders
Extravasation blood
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Vascular disorders
Extremity necrosis
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Vascular disorders
Haematoma
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Vascular disorders
Hypertension
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
22.2%
2/9 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
22.2%
2/9 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
16.7%
2/12 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
33.3%
2/6 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Vascular disorders
Hypotension
|
14.3%
1/7 • Number of events 2 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
14.3%
1/7 • Number of events 3 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 3 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
11.1%
1/9 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
|
Vascular disorders
Pallor
|
14.3%
1/7 • Number of events 1 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/7 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/9 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/12 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
0.00%
0/6 • All-cause mortality was assessed from date of first dose to study completion (up to approximately 33 months). Serious Adverse events and other adverse events were assessed from date of first dose to 112 days after the last dose or until the last study visit, whichever period was longer, up to approximately 226 days.
|
Additional Information
Bristol-Myers Squibb Study Director
Bristol-Myers Squibb
Phone: Please email
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER