Trial Outcomes & Findings for Study to Investigate the Effect of Balovaptan on the QTC Interval in Healthy Subjects (NCT NCT03808298)
NCT ID: NCT03808298
Last Updated: 2020-07-24
Results Overview
Change-from-baseline QTcF (ΔΔQTcF) at dose level B of balovaptan measured on 12-lead ECGs extracted from continuous recordings at the specified time points on Day 14.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
57 participants
Primary outcome timeframe
Baseline (Predose Day 1), Day 14. (Each treatment period is 15 days.)
Results posted on
2020-07-24
Participant Flow
Participant milestones
| Measure |
Treatment Sequence A and B and Either C or D
All participants received Treatment A and Treatment B and either Treatment C or Treatment D.
|
|---|---|
|
Overall Study
STARTED
|
57
|
|
Overall Study
COMPLETED
|
49
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
Treatment Sequence A and B and Either C or D
All participants received Treatment A and Treatment B and either Treatment C or Treatment D.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Positive Urine Drug Screen at Check-in
|
3
|
Baseline Characteristics
Study to Investigate the Effect of Balovaptan on the QTC Interval in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Treatment Sequence A and B and Either C or D
n=57 Participants
All participants received Treatment A and Treatment B and either Treatment C or Treatment D.
|
|---|---|
|
Age, Continuous
|
36 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
52 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Predose Day 1), Day 14. (Each treatment period is 15 days.)Population: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Change-from-baseline QTcF (ΔΔQTcF) at dose level B of balovaptan measured on 12-lead ECGs extracted from continuous recordings at the specified time points on Day 14.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=52 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.75 hours Pre-dose
|
-0.1 ms
Interval -1.89 to 1.64
|
-0.6 ms
Interval -2.35 to 1.18
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Pre-dose
|
-0.1 ms
Interval -1.92 to 1.67
|
0.1 ms
Interval -1.68 to 1.92
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.25 hours Pre-dose
|
0.2 ms
Interval -1.64 to 2.01
|
-0.1 ms
Interval -1.91 to 1.74
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Post-dose
|
-3.3 ms
Interval -5.15 to -1.52
|
-3.9 ms
Interval -5.73 to -2.09
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 1 hours Post-dose
|
-2.5 ms
Interval -4.27 to -0.67
|
-2.3 ms
Interval -4.13 to -0.53
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 2.5 hours Post-dose
|
-1.9 ms
Interval -3.71 to -0.1
|
-3.5 ms
Interval -5.33 to -1.71
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 4 hours Post-dose
|
-1.0 ms
Interval -2.96 to 0.98
|
-2.1 ms
Interval -4.08 to -0.12
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 8 hours Post-dose
|
-9.8 ms
Interval -11.9 to -7.65
|
-9.6 ms
Interval -11.73 to -7.48
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 12 hours Post-dose
|
-6.6 ms
Interval -9.11 to -4.05
|
-7.5 ms
Interval -10.05 to -4.99
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 24 hours Post-dose
|
-2.4 ms
Interval -4.19 to -0.57
|
-2.9 ms
Interval -4.67 to -1.04
|
—
|
SECONDARY outcome
Timeframe: Baseline (Predose Day 1), Day 1. (Each treatment period is 15 days.)Population: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Change-from-baseline QTcF (ΔΔQTcF) at dose level B of balovaptan measured on 12-lead ECGs extracted from continuous recordings at the specified time points on Day 1.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=52 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 0.5 hours Post-dose
|
-2.3 ms
Interval -3.36 to -1.22
|
-3.5 ms
Interval -4.59 to -2.44
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 1 hours Post-dose
|
-1.8 ms
Interval -2.78 to -0.89
|
-2.9 ms
Interval -3.89 to -1.99
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 2.5 hours Post-dose
|
-0.2 ms
Interval -1.39 to 1.04
|
-2.2 ms
Interval -3.43 to -0.99
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 4 hours Post-dose
|
1.1 ms
Interval -0.32 to 2.52
|
-1.4 ms
Interval -2.88 to -0.02
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 8 hours Post-dose
|
-8.4 ms
Interval -10.2 to -6.69
|
-11.0 ms
Interval -12.72 to -9.2
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 12 hours Post-dose
|
-5.5 ms
Interval -7.7 to -3.32
|
-6.9 ms
Interval -9.12 to -4.75
|
—
|
|
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 24 hours Post-dose
|
-1.3 ms
Interval -2.61 to -0.04
|
-3.0 ms
Interval -4.26 to -1.67
|
—
|
SECONDARY outcome
Timeframe: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)Population: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Change-from-baseline QTcF (ΔΔQTcF) at dose level A of balovaptan measured on 12-lead ECGs extracted from continuous recordings at the specified time points on Days 1 and 14.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 0.5 hours Post-dose
|
-2.7 ms
Interval -3.75 to -1.68
|
-3.5 ms
Interval -4.59 to -2.44
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 1 hours Post-dose
|
-1.6 ms
Interval -2.51 to -0.68
|
-2.9 ms
Interval -3.89 to -1.99
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 2.5 hours Post-dose
|
-0.6 ms
Interval -1.74 to 0.62
|
-2.2 ms
Interval -3.43 to -0.99
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 4 hours Post-dose
|
-0.2 ms
Interval -1.55 to 1.22
|
-1.4 ms
Interval -2.88 to -0.02
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 8 hours Post-dose
|
-8.7 ms
Interval -10.4 to -6.97
|
-11.0 ms
Interval -12.72 to -9.2
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 12 hours Post-dose
|
-6.2 ms
Interval -8.37 to -4.12
|
-6.9 ms
Interval -9.12 to -4.75
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 24 hours Post-dose
|
-2.6 ms
Interval -3.85 to -1.33
|
-3.0 ms
Interval -4.26 to -1.67
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.75 hours Pre-dose
|
-1.1 ms
Interval -2.84 to 0.62
|
-0.6 ms
Interval -2.35 to 1.18
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Pre-dose
|
-0.6 ms
Interval -2.37 to 1.14
|
0.1 ms
Interval -1.68 to 1.92
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.25 hours Pre-dose
|
0.2 ms
Interval -1.63 to 1.94
|
-0.1 ms
Interval -1.91 to 1.74
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Post-dose
|
-3.4 ms
Interval -5.22 to -1.66
|
-3.9 ms
Interval -5.73 to -2.09
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 1 hours Post-dose
|
-2.3 ms
Interval -4.01 to -0.49
|
-2.3 ms
Interval -4.13 to -0.53
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 2.5 hours Post-dose
|
-1.7 ms
Interval -3.48 to 0.05
|
-3.5 ms
Interval -5.33 to -1.71
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 4 hours Post-dose
|
-1.5 ms
Interval -3.43 to 0.43
|
-2.1 ms
Interval -4.08 to -0.12
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 8 hours Post-dose
|
-9.1 ms
Interval -11.13 to -6.99
|
-9.6 ms
Interval -11.73 to -7.48
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 12 hours Post-dose
|
-6.9 ms
Interval -9.34 to -4.41
|
-7.5 ms
Interval -10.05 to -4.99
|
—
|
|
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 24 hours Post-dose
|
-2.7 ms
Interval -4.51 to -0.96
|
-2.9 ms
Interval -4.67 to -1.04
|
—
|
SECONDARY outcome
Timeframe: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)Population: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Change-from-baseline heart rate at dose level A and dose level B of balovaptan measured on 12-Lead ECGs extracted from continuous recordings on Days 1 and 14.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
n=52 Participants
Participants received placebo.
|
|---|---|---|---|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 12 hours Post-dose
|
8.7 bpm
Interval 7.31 to 10.01
|
9.2 bpm
Interval 7.83 to 10.59
|
9.8 bpm
Interval 8.41 to 11.17
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 0.5 hours Post-dose
|
0.2 bpm
Interval -0.54 to 0.91
|
0.5 bpm
Interval -0.24 to 1.25
|
0.4 bpm
Interval -0.34 to 1.17
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 1 hours Post-dose
|
0.1 bpm
Interval -0.64 to 0.87
|
0.0 bpm
Interval -0.78 to 0.78
|
0.2 bpm
Interval -0.61 to 0.97
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 2.5 hours Post-dose
|
-0.4 bpm
Interval -1.29 to 0.54
|
-0.3 bpm
Interval -1.28 to 0.6
|
0.1 bpm
Interval -0.85 to 1.04
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 4 hours Post-dose
|
-0.4 bpm
Interval -1.35 to 0.47
|
0.3 bpm
Interval -0.64 to 1.24
|
0.1 bpm
Interval -0.83 to 1.05
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 8 hours Post-dose
|
4.8 bpm
Interval 3.52 to 6.0
|
4.7 bpm
Interval 3.43 to 5.97
|
5.4 bpm
Interval 4.17 to 6.72
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 12 hours Post-dose
|
7.4 bpm
Interval 6.02 to 8.8
|
7.9 bpm
Interval 6.45 to 9.31
|
8.1 bpm
Interval 6.69 to 9.54
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 24 hours Post-dose
|
2.2 bpm
Interval 1.24 to 3.24
|
0.5 bpm
Interval -0.49 to 1.55
|
2.8 bpm
Interval 1.75 to 3.8
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.75 hours Pre-dose
|
-0.6 bpm
Interval -1.81 to 0.64
|
0.9 bpm
Interval -0.34 to 2.16
|
1.6 bpm
Interval 0.35 to 2.86
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Pre-dose
|
-0.1 bpm
Interval -1.36 to 1.09
|
0.3 bpm
Interval -0.91 to 1.59
|
1.6 bpm
Interval 0.32 to 2.82
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.25 hours Pre-dose
|
0.3 bpm
Interval -0.94 to 1.62
|
1.0 bpm
Interval -0.32 to 2.3
|
1.8 bpm
Interval 0.46 to 3.07
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Post-dose
|
0.4 bpm
Interval -0.74 to 1.6
|
1.4 bpm
Interval 0.16 to 2.55
|
2.0 bpm
Interval 0.85 to 3.25
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 1 hours Post-dose
|
0.4 bpm
Interval -0.84 to 1.57
|
1.1 bpm
Interval -0.14 to 2.32
|
2.0 bpm
Interval 0.82 to 3.28
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 2.5 hours Post-dose
|
0.6 bpm
Interval -0.7 to 1.88
|
1.2 bpm
Interval -0.07 to 2.56
|
2.5 bpm
Interval 1.22 to 3.85
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 4 hours Post-dose
|
1.5 bpm
Interval 0.27 to 2.67
|
1.8 bpm
Interval 0.59 to 3.05
|
2.9 bpm
Interval 1.63 to 4.09
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 8 hours Post-dose
|
5.2 bpm
Interval 3.79 to 6.7
|
5.6 bpm
Interval 4.08 to 7.07
|
6.3 bpm
Interval 4.79 to 7.77
|
|
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 24 hours Post-dose
|
2.3 bpm
Interval 0.93 to 3.6
|
1.6 bpm
Interval 0.21 to 2.94
|
3.3 bpm
Interval 1.9 to 4.63
|
SECONDARY outcome
Timeframe: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)Population: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Change-from-baseline PR interval at dose level A and dose level B of balovaptan measured on 12-Lead ECGs extracted from continuous recordings on Day 1 and 14.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
n=52 Participants
Participants received placebo.
|
|---|---|---|---|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 4 hours Post-dose
|
-0.9 ms
Interval -2.95 to 1.05
|
0.9 ms
Interval -1.1 to 2.99
|
-0.2 ms
Interval -2.29 to 1.81
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 8 hours Post-dose
|
-5.1 ms
Interval -6.9 to -3.22
|
-3.7 ms
Interval -5.55 to -1.79
|
-4.3 ms
Interval -6.23 to -2.46
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 12 hours Post-dose
|
-2.8 ms
Interval -4.65 to -0.89
|
-0.9 ms
Interval -2.86 to 0.99
|
-4.2 ms
Interval -6.14 to -2.29
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 24 hours Post-dose
|
0.9 ms
Interval -0.99 to 2.84
|
3.1 ms
Interval 1.18 to 5.08
|
1.1 ms
Interval -0.82 to 3.08
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 0.5 hours Post-dose
|
-1.4 ms
Interval -2.43 to -0.43
|
-0.9 ms
Interval -1.88 to 0.18
|
-0.2 ms
Interval -1.28 to 0.8
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 1 hours Post-dose
|
-0.3 ms
Interval -1.45 to 0.84
|
-0.4 ms
Interval -1.55 to 0.8
|
-0.3 ms
Interval -1.46 to 0.92
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 2.5 hours Post-dose
|
-1.6 ms
Interval -2.79 to -0.4
|
-2.0 ms
Interval -3.22 to -0.74
|
-2.0 ms
Interval -3.26 to -0.79
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 4 hours Post-dose
|
-1.5 ms
Interval -2.76 to -0.33
|
-1.9 ms
Interval -3.12 to -0.62
|
-1.2 ms
Interval -2.44 to 0.07
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 8 hours Post-dose
|
-6.3 ms
Interval -7.8 to -4.72
|
-6.5 ms
Interval -8.08 to -4.91
|
-7.4 ms
Interval -9.02 to -5.84
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 12 hours Post-dose
|
-3.9 ms
Interval -5.75 to -2.09
|
-5.5 ms
Interval -7.39 to -3.6
|
-4.2 ms
Interval -6.1 to -2.32
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 24 hours Post-dose
|
-1.4 ms
Interval -2.76 to -0.01
|
-0.3 ms
Interval -1.73 to 1.07
|
-0.3 ms
Interval -1.7 to 1.11
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.75 hours Pre-dose
|
3.8 ms
Interval 1.84 to 5.69
|
4.5 ms
Interval 2.56 to 6.49
|
3.1 ms
Interval 1.17 to 5.1
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Pre-dose
|
4.1 ms
Interval 2.11 to 6.08
|
5.0 ms
Interval 2.97 to 7.02
|
3.8 ms
Interval 1.75 to 5.81
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.25 hours Pre-dose
|
3.2 ms
Interval 1.24 to 5.21
|
4.5 ms
Interval 2.46 to 6.52
|
3.0 ms
Interval 0.94 to 5.0
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Post-dose
|
2.9 ms
Interval 0.67 to 5.11
|
2.7 ms
Interval 0.44 to 4.98
|
2.9 ms
Interval 0.64 to 5.18
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 1 hours Post-dose
|
3.1 ms
Interval 0.99 to 5.12
|
2.1 ms
Interval -0.04 to 4.19
|
2.6 ms
Interval 0.49 to 4.72
|
|
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 2.5 hours Post-dose
|
0.2 ms
Interval -1.85 to 2.23
|
1.8 ms
Interval -0.25 to 3.92
|
0.7 ms
Interval -1.36 to 2.82
|
SECONDARY outcome
Timeframe: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)Population: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Change-from-baseline QRS interval at dose level A and dose level B of balovapton measured on 12-Lead ECGs extracted from continuous recordings on Days 1 and 14.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
n=52 Participants
Participants received placebo.
|
|---|---|---|---|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 0.5 hours Post-dose
|
-0.1 ms
Interval -0.25 to 0.01
|
-0.1 ms
Interval -0.22 to 0.05
|
0.0 ms
Interval -0.15 to 0.12
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 1 hours Post-dose
|
0.1 ms
Interval -0.06 to 0.2
|
0.1 ms
Interval -0.05 to 0.22
|
-0.1 ms
Interval -0.22 to 0.05
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 2.5 hours Post-dose
|
0.00 ms
Interval -0.13 to 0.17
|
0.00 ms
Interval -0.17 to 0.14
|
0.1 ms
Interval -0.05 to 0.26
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 4 hours Post-dose
|
0.0 ms
Interval -0.17 to 0.14
|
0.1 ms
Interval -0.02 to 0.31
|
0.0 ms
Interval -0.14 to 0.19
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 8 hours Post-dose
|
-0.5 ms
Interval -0.83 to -0.16
|
-0.3 ms
Interval -0.66 to 0.03
|
-0.4 ms
Interval -0.74 to -0.05
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 12 hours Post-dose
|
-0.2 ms
Interval -0.58 to 0.26
|
0.2 ms
Interval -0.25 to 0.63
|
-0.1 ms
Interval -0.55 to 0.32
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 1 24 hours Post-dose
|
0.0 ms
Interval -0.22 to 0.15
|
0.1 ms
Interval -0.04 to 0.33
|
-0.2 ms
Interval -0.37 to 0.01
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.75 hours Pre-dose
|
0.4 ms
Interval 0.03 to 0.79
|
0.6 ms
Interval 0.18 to 0.95
|
0.2 ms
Interval -0.18 to 0.6
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Pre-dose
|
0.4 ms
Interval 0.03 to 0.79
|
0.5 ms
Interval 0.08 to 0.86
|
0.0 ms
Interval -0.35 to 0.42
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.25 hours Pre-dose
|
0.5 ms
Interval 0.15 to 0.92
|
0.5 ms
Interval 0.12 to 0.91
|
0.00 ms
Interval -0.37 to 0.42
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 0.5 hours Post-dose
|
0.5 ms
Interval 0.1 to 0.87
|
0.5 ms
Interval 0.09 to 0.86
|
0.2 ms
Interval -0.19 to 0.59
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 1 hours Post-dose
|
0.6 ms
Interval 0.18 to 0.94
|
0.6 ms
Interval 0.21 to 0.98
|
0.2 ms
Interval -0.19 to 0.58
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 2.5 hours Post-dose
|
0.5 ms
Interval 0.12 to 0.89
|
0.4 ms
Interval -0.04 to 0.75
|
0.0 ms
Interval -0.35 to 0.43
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 4 hours Post-dose
|
0.4 ms
Interval 0.0 to 0.79
|
0.7 ms
Interval 0.25 to 1.06
|
0.0 ms
Interval -0.39 to 0.42
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 8 hours Post-dose
|
0.1 ms
Interval -0.38 to 0.62
|
0.4 ms
Interval -0.14 to 0.88
|
-0.3 ms
Interval -0.77 to 0.25
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 12 hours Post-dose
|
0.6 ms
Interval 0.06 to 1.15
|
0.6 ms
Interval 0.06 to 1.17
|
0.3 ms
Interval -0.23 to 0.89
|
|
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
Day 14 24 hours Post-dose
|
0.6 ms
Interval 0.15 to 0.98
|
0.5 ms
Interval 0.07 to 0.91
|
0.00 ms
Interval -0.38 to 0.46
|
SECONDARY outcome
Timeframe: Up to approximately 20 weeksPopulation: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
The number (percentage) of categorical outliers were participants who had increases in absolute QTcF values \> 450 and ≤ 480 ms, \> 480 and ≤ 500 ms, or \> 500 ms.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
n=52 Participants
Participants received placebo.
|
|---|---|---|---|
|
Number of Categorical Outliers for QTcF
QTcF>450 and <=480 ms
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Categorical Outliers for QTcF
QTcF>480 and <=500 ms
|
0 Participants
|
0 Participants
|
00 Participants
|
|
Number of Categorical Outliers for QTcF
QTcF>500 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 20 weeksPopulation: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Number (percentage) of categorical outliers were participants with a decrease in HR from pre-dose baseline \> 25% to a HR \< 50 bpm; and increase in HR from pre-dose baseline \> 25% to a HR \> 100 bpm.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=52 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=55 Participants
Participants received placebo.
|
Placebo
n=52 Participants
Participants received placebo.
|
|---|---|---|---|
|
Number of Categorical Outliers for HR
HR < 50 (bpm) with a decrease in ΔHR > 25%
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Categorical Outliers for HR
HR > 100 (bpm) with an increase in ΔHR > 25%
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 20 weeksPopulation: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
PR outliers criteria is as an increase of PR from baseline \>25% resulting in PR \>200 ms.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
n=52 Participants
Participants received placebo.
|
|---|---|---|---|
|
Number of Categorical Outliers for PR
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 20 weeksPopulation: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
QRS outlier criteria is an increase of QRS from baseline \>25% resulting in QRS \>120 ms.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
n=52 Participants
Participants received placebo.
|
|---|---|---|---|
|
Number of Categorical Outliers for QRS
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 20 weeksPopulation: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Number (%) of participants falling into each of the T-wave categories: Normal (+), Flat, Notched (+), Biphasic, Normal (-), Notched (-).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
n=52 Participants
Participants received placebo.
|
|---|---|---|---|
|
Number of Treatment Emergent Changes of T-Wave Morphology
Flat T-wave
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Treatment Emergent Changes of T-Wave Morphology
Notched T-wave (+)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Treatment Emergent Changes of T-Wave Morphology
Biphasic T-wave
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Treatment Emergent Changes of T-Wave Morphology
Normal T-wave (-)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Treatment Emergent Changes of T-Wave Morphology
Notched T-wave (-)
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 20 weeksPopulation: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Number (percentage) of participants with treatment emergent changes of U-wave presence.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
n=52 Participants
Participants received placebo.
|
|---|---|---|---|
|
Number of Treatment Emergent Changes of U-Wave Presence
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 14. (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Tmax of Balovaptan
Day 1
|
2.50 h
Interval 1.0 to 8.0
|
1.00 h
Interval 0.5 to 4.0
|
—
|
|
Tmax of Balovaptan
Day 14
|
1.00 h
Interval 1.0 to 8.0
|
1.00 h
Interval 0.5 to 2.5
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 14. (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Tmax of M2 Metabolite
Day 1
|
23.92 h
Interval 12.0 to 23.95
|
23.92 h
Interval 12.0 to 23.95
|
—
|
|
Tmax of M2 Metabolite
Day 14
|
6.00 h
Interval 0.5 to 23.83
|
6.00 h
Interval 0.5 to 12.0
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 14. (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Tmax M3 Metabolite
Day 1
|
23.92 h
Interval 6.0 to 23.95
|
8.00 h
Interval 1.0 to 23.95
|
—
|
|
Tmax M3 Metabolite
Day 14
|
4.00 h
Interval 0.5 to 8.0
|
4.01 h
Interval 0.5 to 8.1
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 14. (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Cmax of Balovaptan
Day 1
|
32.5 ng/mL
Standard Deviation 11.84
|
362.7 ng/mL
Standard Deviation 122.47
|
—
|
|
Cmax of Balovaptan
Day 14
|
89.8 ng/mL
Standard Deviation 28.98
|
613.4 ng/mL
Standard Deviation 191.95
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 14. (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Cmax of M2 Metabolite
Day 1
|
5.69 ng/mL
Standard Deviation 1.828
|
42.75 ng/mL
Standard Deviation 11.965
|
—
|
|
Cmax of M2 Metabolite
Day 14
|
24.77 ng/mL
Standard Deviation 6.057
|
152.83 ng/mL
Standard Deviation 40.855
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 14. (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Cmax of M3 Metabolite
Day 1
|
6.83 ng/mL
Standard Deviation 1.697
|
71.12 ng/mL
Standard Deviation 17.615
|
—
|
|
Cmax of M3 Metabolite
Day 14
|
1005.2 ng/mL
Standard Deviation 233.87
|
5456.9 ng/mL
Standard Deviation 1253.40
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 14 (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
AUC0-24 of Balovaptan
Day 1
|
440.7 h*ng/mL
Standard Deviation 121.92
|
3524.8 h*ng/mL
Standard Deviation 956.14
|
—
|
|
AUC0-24 of Balovaptan
Day 14
|
1127.6 h*ng/mL
Standard Deviation 372.72
|
6377.9 h*ng/mL
Standard Deviation 2149.62
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 14 (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=54 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
AUC0-24 of M2 Metabolite
Day 1
|
90.8 h*ng/mL
Standard Deviation 30.55
|
766.6 h*ng/mL
Standard Deviation 222.20
|
—
|
|
AUC0-24 of M2 Metabolite
Day 14
|
527.5 h*ng/mL
Standard Deviation 123.23
|
3127.0 h*ng/mL
Standard Deviation 807.15
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 14 (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
AUC0-24 of M3 Metabolite
Day 1
|
131.2 h*ng/mL
Standard Deviation 37.49
|
1404.2 h*ng/mL
Standard Deviation 344.31
|
—
|
|
AUC0-24 of M3 Metabolite
Day 14
|
1005.2 h*ng/mL
Standard Deviation 233.87
|
5456.9 h*ng/mL
Standard Deviation 1253.40
|
—
|
SECONDARY outcome
Timeframe: Days 2 (Treatment C) or 15 (Treatment D). (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=26 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=26 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Tmax of Moxifloxacin
|
2.50 h
Interval 0.5 to 4.02
|
1.78 h
Interval 0.5 to 4.02
|
—
|
SECONDARY outcome
Timeframe: Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=26 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=26 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Cmax of Moxifloxacin
|
2056.9 ng/mL
Standard Deviation 437.64
|
2058.8 ng/mL
Standard Deviation 525.99
|
—
|
SECONDARY outcome
Timeframe: Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.)Population: PK population included all participants who received at least 1 dose of investigational product and had at least 1 evaluable pharmacokinetic (PK) plasma concentration for any of balovaptan, M2 and M3 (and moxifloxacin, when applicable).
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=26 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=26 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
AUC0-24 of Moxifloxacin
|
22503.9 h*ng/mL
Standard Deviation 4103.73
|
24103.1 h*ng/mL
Standard Deviation 5169.94
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 14. (Each treatment period is 15 days.)Population: PK/QTc population included all participants who were in both the QT/QTc and PK populations with at least 1 pair of post-dose PK and QTcF data from the same time point.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of Balovaptan From Concentration-QTc Analysis
|
1.06 ms
Interval -0.2 to 2.31
|
0.70 ms
Interval -1.49 to 2.88
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 14. (Each treatment period is 15 days.)Population: PK/QTc population included all participants who were in both the QT/QTc and PK populations with at least 1 pair of post-dose PK and QTcF data from the same time point.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of M2 From Concentration-QTc Analysis
|
1.01 ms
Interval -0.3 to 2.31
|
0.27 ms
Interval -2.47 to 3.02
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 14. (Each treatment period is 15 days.)Population: PK/QTc population included all participants who were in both the QT/QTc and PK populations with at least 1 pair of post-dose PK and QTcF data from the same time point.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=55 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentration for M3 From Concentration-QTc Analysis
|
1.05 ms
Interval -0.17 to 2.27
|
0.23 ms
Interval -2.38 to 2.83
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 15. (Each treatment period is 15 days.)Population: QT/QTc population included all participants in the Safety population with ECG measurements at baseline as well as on treatment with at least 1 post-dose time point with a valid ΔQTcF value.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=52 Participants
Participants received dose level of B balovaptan.
|
Placebo
n=52 Participants
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
0.5 hours Post-dose
|
-2.0 ms
Interval -4.01 to 0.02
|
-3.2 ms
Interval -5.21 to -1.18
|
—
|
|
Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
1 hours Post-dose
|
3.4 ms
Interval 1.14 to 5.69
|
-2.0 ms
Interval -4.29 to 0.27
|
—
|
|
Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
2.5 hours Post-dose
|
6.2 ms
Interval 4.28 to 8.16
|
-2.3 ms
Interval -4.27 to -0.38
|
—
|
|
Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
4 hours Post-dose
|
7.5 ms
Interval 5.54 to 9.44
|
-1.1 ms
Interval -3.06 to 0.84
|
—
|
|
Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
8 hours Post-dose
|
-1.3 ms
Interval -3.53 to 0.86
|
-9.9 ms
Interval -12.05 to -7.66
|
—
|
|
Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
12 hours Post-dose
|
0.1 ms
Interval -2.16 to 2.27
|
-6.8 ms
Interval -9.05 to -4.61
|
—
|
|
Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
24 hours Post-dose
|
3.9 ms
Interval 2.14 to 5.75
|
-2.2 ms
Interval -3.97 to -0.37
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 20 weeks.Population: Groups C\&D together are positive control to balovaptan. Moxifloxacin is given in a nested cross-over way using a joint placebo/positive control period, half subjects dosed with moxifloxacin on Day 2 and other half dosed on Day 15.
Outcome measures
| Measure |
Dose Level B of Balovaptan
n=57 Participants
Participants received dose level of B balovaptan.
|
Placebo
Participants received placebo.
|
Placebo
Participants received placebo.
|
|---|---|---|---|
|
Percentage of Participants With Treatment Emergent Adverse Events
|
42.1 Percentage of Participants
|
—
|
—
|
Adverse Events
Treatment A Dose Level A
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Treatment B Dose Level B
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Treatment C Placebo + Moxifloxacin 400 mg Day 2
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Treatment D Placebo + Moxifloxacin 400 mg Day 15
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
All Participants
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A Dose Level A
n=55 participants at risk
Participants in treatment A received balovaptan at dose level A.
|
Treatment B Dose Level B
n=52 participants at risk
Participants in treatment B received balovaptan at dose level B.
|
Treatment C Placebo + Moxifloxacin 400 mg Day 2
n=26 participants at risk
Participants in treatment C received placebo plus 400 mg of moxifloxacin on Day 2.
|
Treatment D Placebo + Moxifloxacin 400 mg Day 15
n=26 participants at risk
Participants in treatment D received placebo plus 400 mg moxifloxacin on Day 15.
|
All Participants
n=57 participants at risk
All participants received Treatment A and Treatment B and either Treatment C or Treatment D.
|
|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
16.4%
9/55 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
5.8%
3/52 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
19.2%
5/26 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
15.4%
4/26 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
26.3%
15/57 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
|
Gastrointestinal disorders
Constipation
|
5.5%
3/55 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
0.00%
0/52 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
3.8%
1/26 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
11.5%
3/26 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
8.8%
5/57 • From the first study drug to the data cutoff date: 13 July 2019 (up to 20 weeks)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER