Healthy Volunteers
Conditions
Brief summary
This was a single-center, multiple-dose, randomized, double-blind, placebo-controlled, positive-controlled, twelve sequence, 3-period cross-over study to investigate the effect of balovaptan on the QTc interval in healthy subjects.
Interventions
DRUGBalovaptan therapeutic dose Treatment A
Days 1-14: A single once daily dose at dose level A of balovaptan for 14 days
DRUGBalovaptan supra-therapeutic dose Treatment B
Days 1-14: A single once daily oral dose at dose level B of balovaptan for 14 days.
DRUGActive control [moxifloxacin] on Day 2 Treatment C
Day 2: A single oral dose of 400 mg moxifloxacin capsule.
DRUGActive control [Moxifloxacin] on Day 15 Treatment D
Day 15: A single oral dose of 400 mg moxifloxacin capsule.
DRUGPlacebo for Balovaptan Treatment C
Days 1-14: Matching placebo for balovaptan for 14 days.
DRUGPlacebo for Balovaptan Treatment D
Days 1-14: Matching placebo for balovaptan for 14 days.
DRUGPlacebo for Moxifloxacin Treatment A
Day 2 and 15: A single oral dose of a matching placebo capsule for moxifloxacin.
DRUGPlacebo for Moxifloxacin Treatment B
Days 2 and 15: Single oral dose of a matching placebo capsule of moxifloxacin.
DRUGMoxifloxacin Treatment C
Day 2: A single oral dose of 400 mg moxifloxacin capsule.
DRUGPlacebo for Moxifloxacin Treatment C
Day 15: A single oral dose of a matching placebo capsule for moxifloxacin.
DRUGPlacebo for Moxifloxacin Treatment D
Day 2: A single oral dose of a matching placebo capsule for moxifloxacin.
DRUGMoxifloxacin Treatment D
Day 15: A single oral dose of 400 mg moxifloxacin capsule.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female subjects. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, urinalysis, and serology. * Body Mass Index of 18 to 30 kg/m2, inclusive. * For women of childbearing potential: agreement to use at least 1 acceptable form of contraception during the entire study and for 90 days following last dose of study drug. * For men: vasectomized, agreement to remain abstinent or use of a condom during intercourse. Must also agree to refrain from donating sperm. * Fluent in English.
Exclusion criteria
* If female, a positive pregnancy test at screening or prior to Day 1 of any Treatment Period. * Lactating women. * Any condition or disease detected during the medical interview / physical examination that would render the subject unsuitable for the study, place the subject at undue risk or interfere with the ability of the subject to complete the study in the opinion of the Investigator or designee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Baseline (Predose Day 1), Day 14. (Each treatment period is 15 days.) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings | Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.) | 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. |
| Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.) | 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. |
| Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.) | 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. |
| Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.) | 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. |
| Number of Categorical Outliers for QTcF | Up to approximately 20 weeks | 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. |
| Number of Categorical Outliers for HR | Up to approximately 20 weeks | 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. |
| Number of Categorical Outliers for PR | Up to approximately 20 weeks | PR outliers criteria is as an increase of PR from baseline \>25% resulting in PR \>200 ms. |
| Number of Categorical Outliers for QRS | Up to approximately 20 weeks | QRS outlier criteria is an increase of QRS from baseline \>25% resulting in QRS \>120 ms. |
| Number of Treatment Emergent Changes of T-Wave Morphology | Up to approximately 20 weeks | Number (%) of participants falling into each of the T-wave categories: Normal (+), Flat, Notched (+), Biphasic, Normal (-), Notched (-). |
| Number of Treatment Emergent Changes of U-Wave Presence | Up to approximately 20 weeks | Number (percentage) of participants with treatment emergent changes of U-wave presence. |
| Tmax of Balovaptan | Day 1 and Day 14. (Each treatment period is 15 days.) | — |
| Tmax of M2 Metabolite | Day 1 and Day 14. (Each treatment period is 15 days.) | — |
| Tmax M3 Metabolite | Day 1 and Day 14. (Each treatment period is 15 days.) | — |
| Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Baseline (Predose Day 1), Day 1. (Each treatment period is 15 days.) | 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. |
| Cmax of M2 Metabolite | Day 1 and Day 14. (Each treatment period is 15 days.) | — |
| Cmax of M3 Metabolite | Day 1 and Day 14. (Each treatment period is 15 days.) | — |
| AUC0-24 of Balovaptan | Day 1 and Day 14 (Each treatment period is 15 days.) | — |
| AUC0-24 of M2 Metabolite | Day 1 and Day 14 (Each treatment period is 15 days.) | — |
| AUC0-24 of M3 Metabolite | Day 1 and Day 14 (Each treatment period is 15 days.) | — |
| Tmax of Moxifloxacin | Days 2 (Treatment C) or 15 (Treatment D). (Each treatment period is 15 days.) | — |
| Cmax of Moxifloxacin | Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.) | — |
| AUC0-24 of Moxifloxacin | Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.) | — |
| Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of Balovaptan From Concentration-QTc Analysis | Baseline, Day 14. (Each treatment period is 15 days.) | — |
| Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of M2 From Concentration-QTc Analysis | Baseline, Day 14. (Each treatment period is 15 days.) | — |
| Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentration for M3 From Concentration-QTc Analysis | Baseline, Day 14. (Each treatment period is 15 days.) | — |
| Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | Baseline, Day 15. (Each treatment period is 15 days.) | — |
| Percentage of Participants With Treatment Emergent Adverse Events | Up to approximately 20 weeks. | — |
| Cmax of Balovaptan | Day 1 and Day 14. (Each treatment period is 15 days.) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Positive Urine Drug Screen at Check-in | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment Sequence A and B and Either C or D |
|---|---|
| Age, Continuous | 36.9 Years STANDARD_DEVIATION 10.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 52 | 0 / 26 | 0 / 26 | 0 / 57 |
| other Total, other adverse events | 11 / 55 | 3 / 52 | 6 / 26 | 5 / 26 | 18 / 57 |
| serious Total, serious adverse events | 0 / 55 | 0 / 52 | 0 / 26 | 0 / 26 | 0 / 57 |
Outcome results
Primary
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | -9.6 ms |
| 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 | -0.6 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | -3.5 ms |
| Placebo | 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 |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | -2.9 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | -0.1 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | -2.1 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | -3.9 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | -7.5 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | -2.3 ms |
90% CI: [-1.99, 2.9]
90% CI: [-2.73, 2.24]
90% CI: [-2.25, 2.79]
90% CI: [-1.94, 3.09]
90% CI: [-2.62, 2.35]
90% CI: [-0.88, 4.11]
90% CI: [-1.63, 3.85]
90% CI: [-3.13, 2.79]
90% CI: [-2.6, 4.47]
90% CI: [-2.03, 2.98]
Secondary
AUC0-24 of Balovaptan
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level B of Balovaptan | AUC0-24 of Balovaptan | Day 14 | 1127.6 h*ng/mL | Standard Deviation 372.72 |
| Dose Level B of Balovaptan | AUC0-24 of Balovaptan | Day 1 | 440.7 h*ng/mL | Standard Deviation 121.92 |
| Placebo | AUC0-24 of Balovaptan | Day 1 | 3524.8 h*ng/mL | Standard Deviation 956.14 |
| Placebo | AUC0-24 of Balovaptan | Day 14 | 6377.9 h*ng/mL | Standard Deviation 2149.62 |
Secondary
AUC0-24 of M2 Metabolite
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level B of Balovaptan | AUC0-24 of M2 Metabolite | Day 1 | 90.8 h*ng/mL | Standard Deviation 30.55 |
| Dose Level B of Balovaptan | AUC0-24 of M2 Metabolite | Day 14 | 527.5 h*ng/mL | Standard Deviation 123.23 |
| Placebo | AUC0-24 of M2 Metabolite | Day 1 | 766.6 h*ng/mL | Standard Deviation 222.2 |
| Placebo | AUC0-24 of M2 Metabolite | Day 14 | 3127.0 h*ng/mL | Standard Deviation 807.15 |
Secondary
AUC0-24 of M3 Metabolite
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level B of Balovaptan | AUC0-24 of M3 Metabolite | Day 1 | 131.2 h*ng/mL | Standard Deviation 37.49 |
| Dose Level B of Balovaptan | AUC0-24 of M3 Metabolite | Day 14 | 1005.2 h*ng/mL | Standard Deviation 233.87 |
| Placebo | AUC0-24 of M3 Metabolite | Day 1 | 1404.2 h*ng/mL | Standard Deviation 344.31 |
| Placebo | AUC0-24 of M3 Metabolite | Day 14 | 5456.9 h*ng/mL | Standard Deviation 1253.4 |
Secondary
AUC0-24 of Moxifloxacin
Time frame: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Level B of Balovaptan | AUC0-24 of Moxifloxacin | 22503.9 h*ng/mL | Standard Deviation 4103.73 |
| Placebo | AUC0-24 of Moxifloxacin | 24103.1 h*ng/mL | Standard Deviation 5169.94 |
Secondary
Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | 0.4 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | 2.2 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | 0.1 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 0.5 hours Post-dose | 0.2 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.75 hours Pre-dose | -0.6 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | 5.2 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | 0.4 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Pre-dose | -0.1 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | -0.4 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | 0.3 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | 2.3 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | 1.5 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | 4.8 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | 8.7 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | 0.6 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | 7.4 bpm |
| Dose Level B of Balovaptan | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | -0.4 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | 1.4 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 0.5 hours Post-dose | 0.5 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | 0.0 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | -0.3 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | 0.3 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | 4.7 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | 7.9 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | 0.5 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.75 hours Pre-dose | 0.9 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Pre-dose | 0.3 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | 1.0 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | 1.1 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | 1.2 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | 1.8 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | 5.6 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | 9.2 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | 1.6 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | 0.2 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | 2.0 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | 5.4 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | 3.3 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | 2.5 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | 0.1 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | 9.8 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | 2.9 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | 0.1 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 0.5 hours Post-dose | 0.4 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Pre-dose | 1.6 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | 6.3 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | 1.8 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.75 hours Pre-dose | 1.6 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | 2.8 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | 2.0 bpm |
| Placebo | Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | 8.1 bpm |
90% CI: [-1.2, 0.73]
90% CI: [-1.08, 0.96]
90% CI: [-1.73, 0.78]
90% CI: [-1.8, 0.7]
90% CI: [-2.42, 1.05]
90% CI: [-2.66, 1.24]
90% CI: [-1.91, 0.85]
90% CI: [-3.9, -0.48]
90% CI: [-3.41, 0]
90% CI: [-3.21, 0.36]
90% CI: [-3.25, 0.01]
90% CI: [-3.36, -0.01]
90% CI: [-3.75, -0.14]
90% CI: [-2.42, 1.03]
90% CI: [-3.06, 0.29]
90% CI: [-3.08, 1.01]
90% CI: [-3.03, 0.76]
90% CI: [-2.96, 0.49]
90% CI: [-2.58, 1.02]
90% CI: [-2.87, 0.87]
90% CI: [-0.89, 1.07]
90% CI: [-1.21, 0.86]
90% CI: [-1.71, 0.83]
90% CI: [-1.07, 1.46]
90% CI: [-2.5, 1]
90% CI: [-2.22, 1.74]
90% CI: [-3.63, -0.85]
90% CI: [-2.34, 0.95]
90% CI: [-2.65, 0.73]
90% CI: [-3.11, 0.53]
90% CI: [-2.73, 0.66]
90% CI: [-2.77, 1.37]
90% CI: [-2.5, 1.33]
90% CI: [-3.57, 0.2]
Secondary
Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | 3.1 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | -1.4 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | -0.3 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 0.5 hours Post-dose | -1.4 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.75 hours Pre-dose | 3.8 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | -5.1 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | 2.9 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Pre-dose | 4.1 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | -1.5 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | 3.2 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | 0.9 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | -0.9 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | -6.3 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | -2.8 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | 0.2 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | -3.9 ms |
| Dose Level B of Balovaptan | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | -1.6 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | 2.7 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 0.5 hours Post-dose | -0.9 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | -0.4 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | -2.0 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | -1.9 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | -6.5 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | -5.5 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | -0.3 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.75 hours Pre-dose | 4.5 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Pre-dose | 5.0 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | 4.5 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | 2.1 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | 1.8 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | 0.9 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | -3.7 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | -0.9 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | 3.1 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | -0.3 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | 2.6 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | -7.4 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | 1.1 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | 0.7 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | -1.2 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | -4.2 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | -0.2 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | -2.0 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 0.5 hours Post-dose | -0.2 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Pre-dose | 3.8 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | -4.3 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | 3.0 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.75 hours Pre-dose | 3.1 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | -0.3 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | 2.9 ms |
| Placebo | Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | -4.2 ms |
90% CI: [-2.56, 0.17]
90% CI: [-1.62, 1.55]
90% CI: [-1.22, 2.09]
90% CI: [-2.04, 1.33]
90% CI: [-1, 3.33]
90% CI: [-2.3, 2.88]
90% CI: [-3, 0.81]
90% CI: [-2.08, 3.35]
90% CI: [-2.48, 3.12]
90% CI: [-2.55, 3.06]
90% CI: [-3.17, 3.12]
90% CI: [-2.47, 3.37]
90% CI: [-3.42, 2.34]
90% CI: [-3.54, 2.12]
90% CI: [-3.31, 1.88]
90% CI: [-1.21, 4.09]
90% CI: [-2.9, 2.49]
90% CI: [-2, 0.77]
90% CI: [-1.71, 1.5]
90% CI: [-1.64, 1.73]
90% CI: [-2.39, 1.02]
90% CI: [-1.26, 3.13]
90% CI: [-3.92, 1.35]
90% CI: [-1.96, 1.89]
90% CI: [-1.34, 4.13]
90% CI: [-1.61, 4.05]
90% CI: [-1.32, 4.35]
90% CI: [-3.38, 2.97]
90% CI: [-3.48, 2.42]
90% CI: [-1.81, 4.02]
90% CI: [-1.67, 4.04]
90% CI: [-1.95, 3.29]
90% CI: [0.6, 5.96]
90% CI: [-0.72, 4.72]
Secondary
Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | 0.6 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | 0.0 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 0.5 hours Post-dose | -0.1 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | 0.1 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.75 hours Pre-dose | 0.4 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | 0.1 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | 0.5 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Pre-dose | 0.4 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | 0.0 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | 0.5 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | 0.6 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | 0.4 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | -0.5 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | 0.6 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | 0.5 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | -0.2 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | 0.00 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | 0.5 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | 0.1 ms |
| 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 |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | 0.00 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | 0.1 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | -0.3 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | 0.2 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | 0.1 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.75 hours Pre-dose | 0.6 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Pre-dose | 0.5 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | 0.5 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | 0.6 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | 0.4 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | 0.7 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | 0.4 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | 0.6 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | 0.5 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | -0.1 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 1 hours Post-dose | 0.2 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | -0.4 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 24 hours Post-dose | 0.00 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 2.5 hours Post-dose | 0.0 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | 0.0 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 12 hours Post-dose | 0.3 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 4 hours Post-dose | 0.0 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | 0.1 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 0.5 hours Post-dose | 0.0 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Pre-dose | 0.0 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 8 hours Post-dose | -0.3 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.25 hours Pre-dose | 0.00 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.75 hours Pre-dose | 0.2 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | -0.2 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 14 0.5 hours Post-dose | 0.2 ms |
| Placebo | Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | -0.1 ms |
90% CI: [-0.29, 0.07]
90% CI: [-0.02, 0.34]
90% CI: [-0.3, 0.12]
90% CI: [-0.26, 0.18]
90% CI: [-0.57, 0.38]
90% CI: [-0.65, 0.56]
90% CI: [-0.11, 0.4]
90% CI: [-0.34, 0.74]
90% CI: [-0.17, 0.91]
90% CI: [-0.04, 1.05]
90% CI: [-0.26, 0.82]
90% CI: [-0.18, 0.9]
Comparison: Placebo-corrected change-from-baseline QRS (ms) at Day 14 2.5 Hours Post-dose90% CI: [-0.08, 1]
90% CI: [-0.19, 0.94]
90% CI: [-0.33, 1.1]
90% CI: [-0.5, 1.06]
90% CI: [-0.06, 1.11]
90% CI: [-0.25, 0.11]
90% CI: [0, 0.36]
90% CI: [-0.34, 0.09]
90% CI: [-0.1, 0.34]
90% CI: [-0.4, 0.57]
90% CI: [-0.31, 0.93]
90% CI: [0.07, 0.58]
90% CI: [-0.19, 0.9]
90% CI: [-0.11, 0.98]
90% CI: [-0.06, 1.05]
90% CI: [-0.27, 0.82]
90% CI: [-0.14, 0.94]
90% CI: [-0.24, 0.86]
90% CI: [0.07, 1.2]
90% CI: [-0.1, 1.35]
90% CI: [-0.5, 1.07]
90% CI: [-0.14, 1.04]
Secondary
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 24 hours Post-dose | -3.0 ms |
| 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 | -3.5 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 1 hours Post-dose | -2.9 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 2.5 hours Post-dose | -2.2 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 4 hours Post-dose | -1.4 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 8 hours Post-dose | -11.0 ms |
| Placebo | Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings | Day 1 12 hours Post-dose | -6.9 ms |
90% CI: [-0.19, 2.64]
90% CI: [-0.12, 2.33]
90% CI: [0.4, 3.67]
90% CI: [0.6, 4.49]
90% CI: [0.09, 4.94]
90% CI: [-1.62, 4.47]
90% CI: [-0.1, 3.39]
Secondary
Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 2.5 hours Post-dose | 6.2 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 8 hours Post-dose | -1.3 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 1 hours Post-dose | 3.4 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 12 hours Post-dose | 0.1 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 4 hours Post-dose | 7.5 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 24 hours Post-dose | 3.9 ms |
| Dose Level B of Balovaptan | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 0.5 hours Post-dose | -2.0 ms |
| Placebo | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 24 hours Post-dose | -2.2 ms |
| Placebo | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 0.5 hours Post-dose | -3.2 ms |
| Placebo | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 1 hours Post-dose | -2.0 ms |
| Placebo | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 2.5 hours Post-dose | -2.3 ms |
| Placebo | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 4 hours Post-dose | -1.1 ms |
| Placebo | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 8 hours Post-dose | -9.9 ms |
| Placebo | Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records | 12 hours Post-dose | -6.8 ms |
90% CI: [-1.64, 4.04]
90% CI: [2.22, 8.63]
90% CI: [5.81, 11.28]
90% CI: [5.86, 11.34]
90% CI: [5.43, 11.61]
90% CI: [3.76, 10]
90% CI: [3.58, 8.62]
Secondary
Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Dose Level B of Balovaptan | 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 |
| Placebo | 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 | -2.9 ms |
| 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 | -3.5 ms |
| Placebo | 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 | -2.9 ms |
| Placebo | 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 | -2.2 ms |
| Placebo | 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 | -1.4 ms |
| Placebo | 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 | -11.0 ms |
| Placebo | 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 | -6.9 ms |
| Placebo | 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 | -3.0 ms |
| Placebo | 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 | -0.6 ms |
| Placebo | 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 | 0.1 ms |
| Placebo | 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 | -0.1 ms |
| Placebo | 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 | -3.9 ms |
| Placebo | 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 |
| Placebo | 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 | -3.5 ms |
| Placebo | 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 | -2.1 ms |
| Placebo | 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 | -9.6 ms |
| Placebo | 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 | -7.5 ms |
90% CI: [-0.6, 2.2]
90% CI: [0.13, 2.55]
90% CI: [0.04, 3.27]
90% CI: [-0.64, 3.2]
90% CI: [-0.13, 4.67]
90% CI: [-2.31, 3.7]
90% CI: [-1.35, 2.1]
90% CI: [-2.94, 1.89]
90% CI: [-3.19, 1.72]
90% CI: [-2.26, 2.74]
90% CI: [-2.02, 2.96]
90% CI: [-2.39, 2.54]
90% CI: [-0.67, 4.28]
90% CI: [-2.11, 3.31]
90% CI: [-2.38, 3.47]
90% CI: [-2.85, 4.14]
90% CI: [-2.36, 2.6]
Secondary
Cmax of Balovaptan
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level B of Balovaptan | Cmax of Balovaptan | Day 1 | 32.5 ng/mL | Standard Deviation 11.84 |
| Dose Level B of Balovaptan | Cmax of Balovaptan | Day 14 | 89.8 ng/mL | Standard Deviation 28.98 |
| Placebo | Cmax of Balovaptan | Day 1 | 362.7 ng/mL | Standard Deviation 122.47 |
| Placebo | Cmax of Balovaptan | Day 14 | 613.4 ng/mL | Standard Deviation 191.95 |
Secondary
Cmax of M2 Metabolite
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level B of Balovaptan | Cmax of M2 Metabolite | Day 1 | 5.69 ng/mL | Standard Deviation 1.828 |
| Dose Level B of Balovaptan | Cmax of M2 Metabolite | Day 14 | 24.77 ng/mL | Standard Deviation 6.057 |
| Placebo | Cmax of M2 Metabolite | Day 1 | 42.75 ng/mL | Standard Deviation 11.965 |
| Placebo | Cmax of M2 Metabolite | Day 14 | 152.83 ng/mL | Standard Deviation 40.855 |
Secondary
Cmax of M3 Metabolite
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level B of Balovaptan | Cmax of M3 Metabolite | Day 1 | 6.83 ng/mL | Standard Deviation 1.697 |
| Dose Level B of Balovaptan | Cmax of M3 Metabolite | Day 14 | 1005.2 ng/mL | Standard Deviation 233.87 |
| Placebo | Cmax of M3 Metabolite | Day 1 | 71.12 ng/mL | Standard Deviation 17.615 |
| Placebo | Cmax of M3 Metabolite | Day 14 | 5456.9 ng/mL | Standard Deviation 1253.4 |
Secondary
Cmax of Moxifloxacin
Time frame: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Level B of Balovaptan | Cmax of Moxifloxacin | 2056.9 ng/mL | Standard Deviation 437.64 |
| Placebo | Cmax of Moxifloxacin | 2058.8 ng/mL | Standard Deviation 525.99 |
Secondary
Number of Categorical Outliers for HR
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.
Time frame: Up to approximately 20 weeks
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level B of Balovaptan | Number of Categorical Outliers for HR | HR < 50 (bpm) with a decrease in ΔHR > 25% | 0 Participants |
| Dose Level B of Balovaptan | Number of Categorical Outliers for HR | HR > 100 (bpm) with an increase in ΔHR > 25% | 0 Participants |
| Placebo | Number of Categorical Outliers for HR | HR < 50 (bpm) with a decrease in ΔHR > 25% | 0 Participants |
| Placebo | Number of Categorical Outliers for HR | HR > 100 (bpm) with an increase in ΔHR > 25% | 0 Participants |
| Placebo | Number of Categorical Outliers for HR | HR < 50 (bpm) with a decrease in ΔHR > 25% | 0 Participants |
| Placebo | Number of Categorical Outliers for HR | HR > 100 (bpm) with an increase in ΔHR > 25% | 0 Participants |
Secondary
Number of Categorical Outliers for PR
PR outliers criteria is as an increase of PR from baseline \>25% resulting in PR \>200 ms.
Time frame: Up to approximately 20 weeks
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level B of Balovaptan | Number of Categorical Outliers for PR | 0 Participants |
| Placebo | Number of Categorical Outliers for PR | 0 Participants |
| Placebo | Number of Categorical Outliers for PR | 0 Participants |
Secondary
Number of Categorical Outliers for QRS
QRS outlier criteria is an increase of QRS from baseline \>25% resulting in QRS \>120 ms.
Time frame: Up to approximately 20 weeks
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level B of Balovaptan | Number of Categorical Outliers for QRS | 0 Participants |
| Placebo | Number of Categorical Outliers for QRS | 0 Participants |
| Placebo | Number of Categorical Outliers for QRS | 0 Participants |
Secondary
Number of Categorical Outliers for QTcF
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.
Time frame: Up to approximately 20 weeks
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level B of Balovaptan | Number of Categorical Outliers for QTcF | QTcF>480 and <=500 ms | 0 Participants |
| Dose Level B of Balovaptan | Number of Categorical Outliers for QTcF | QTcF>450 and <=480 ms | 0 Participants |
| Dose Level B of Balovaptan | Number of Categorical Outliers for QTcF | QTcF>500 ms | 0 Participants |
| Placebo | Number of Categorical Outliers for QTcF | QTcF>480 and <=500 ms | 0 Participants |
| Placebo | Number of Categorical Outliers for QTcF | QTcF>450 and <=480 ms | 1 Participants |
| Placebo | Number of Categorical Outliers for QTcF | QTcF>500 ms | 0 Participants |
| Placebo | Number of Categorical Outliers for QTcF | QTcF>450 and <=480 ms | 0 Participants |
| Placebo | Number of Categorical Outliers for QTcF | QTcF>500 ms | 0 Participants |
| Placebo | Number of Categorical Outliers for QTcF | QTcF>480 and <=500 ms | 00 Participants |
Secondary
Number of Treatment Emergent Changes of T-Wave Morphology
Number (%) of participants falling into each of the T-wave categories: Normal (+), Flat, Notched (+), Biphasic, Normal (-), Notched (-).
Time frame: Up to approximately 20 weeks
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level B of Balovaptan | Number of Treatment Emergent Changes of T-Wave Morphology | Normal T-wave (-) | 0 Participants |
| Dose Level B of Balovaptan | Number of Treatment Emergent Changes of T-Wave Morphology | Biphasic T-wave | 0 Participants |
| Dose Level B of Balovaptan | Number of Treatment Emergent Changes of T-Wave Morphology | Flat T-wave | 0 Participants |
| Dose Level B of Balovaptan | Number of Treatment Emergent Changes of T-Wave Morphology | Notched T-wave (+) | 0 Participants |
| Dose Level B of Balovaptan | Number of Treatment Emergent Changes of T-Wave Morphology | Notched T-wave (-) | 0 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Biphasic T-wave | 1 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Flat T-wave | 1 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Notched T-wave (+) | 0 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Normal T-wave (-) | 0 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Notched T-wave (-) | 0 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Notched T-wave (-) | 0 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Normal T-wave (-) | 0 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Flat T-wave | 1 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Biphasic T-wave | 0 Participants |
| Placebo | Number of Treatment Emergent Changes of T-Wave Morphology | Notched T-wave (+) | 0 Participants |
Secondary
Number of Treatment Emergent Changes of U-Wave Presence
Number (percentage) of participants with treatment emergent changes of U-wave presence.
Time frame: Up to approximately 20 weeks
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level B of Balovaptan | Number of Treatment Emergent Changes of U-Wave Presence | 0 Participants |
| Placebo | Number of Treatment Emergent Changes of U-Wave Presence | 0 Participants |
| Placebo | Number of Treatment Emergent Changes of U-Wave Presence | 0 Participants |
Secondary
Percentage of Participants With Treatment Emergent Adverse Events
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level B of Balovaptan | Percentage of Participants With Treatment Emergent Adverse Events | 42.1 Percentage of Participants |
Secondary
Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentration for M3 From Concentration-QTc Analysis
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dose Level B of Balovaptan | Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentration for M3 From Concentration-QTc Analysis | 1.05 ms |
| Placebo | Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentration for M3 From Concentration-QTc Analysis | 0.23 ms |
Secondary
Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of Balovaptan From Concentration-QTc Analysis
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dose Level B of Balovaptan | Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of Balovaptan From Concentration-QTc Analysis | 1.06 ms |
| Placebo | Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of Balovaptan From Concentration-QTc Analysis | 0.70 ms |
Secondary
Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of M2 From Concentration-QTc Analysis
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dose Level B of Balovaptan | Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of M2 From Concentration-QTc Analysis | 1.01 ms |
| Placebo | Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of M2 From Concentration-QTc Analysis | 0.27 ms |
Secondary
Tmax M3 Metabolite
Time frame: 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).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | Tmax M3 Metabolite | Day 14 | 4.00 h |
| Dose Level B of Balovaptan | Tmax M3 Metabolite | Day 1 | 23.92 h |
| Placebo | Tmax M3 Metabolite | Day 14 | 4.01 h |
| Placebo | Tmax M3 Metabolite | Day 1 | 8.00 h |
Secondary
Tmax of Balovaptan
Time frame: 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).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | Tmax of Balovaptan | Day 1 | 2.50 h |
| Dose Level B of Balovaptan | Tmax of Balovaptan | Day 14 | 1.00 h |
| Placebo | Tmax of Balovaptan | Day 1 | 1.00 h |
| Placebo | Tmax of Balovaptan | Day 14 | 1.00 h |
Secondary
Tmax of M2 Metabolite
Time frame: 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).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Level B of Balovaptan | Tmax of M2 Metabolite | Day 1 | 23.92 h |
| Dose Level B of Balovaptan | Tmax of M2 Metabolite | Day 14 | 6.00 h |
| Placebo | Tmax of M2 Metabolite | Day 1 | 23.92 h |
| Placebo | Tmax of M2 Metabolite | Day 14 | 6.00 h |
Secondary
Tmax of Moxifloxacin
Time frame: 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).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Level B of Balovaptan | Tmax of Moxifloxacin | 2.50 h |
| Placebo | Tmax of Moxifloxacin | 1.78 h |