A Single-Center, Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study to Investigate the Effect of Balovaptan on the QTC Interval in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 57
- Locations
- 1
- Primary Endpoint
- Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts 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.
Arms & Interventions
Treatment Sequence 3: B, A, C
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 3: B, A, C
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 3: B, A, C
Intervention: Placebo for Balovaptan Treatment C (Drug)
Treatment Sequence 1: A, B, C
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 1: A, B, C
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 1: A, B, C
Intervention: Active control [moxifloxacin] on Day 2 Treatment C (Drug)
Treatment Sequence 1: A, B, C
Intervention: Placebo for Balovaptan Treatment C (Drug)
Treatment Sequence 1: A, B, C
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 1: A, B, C
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 1: A, B, C
Intervention: Moxifloxacin Treatment C (Drug)
Treatment Sequence 1: A, B, C
Intervention: Placebo for Moxifloxacin Treatment C (Drug)
Treatment Sequence 2: A, C, B
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 2: A, C, B
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 2: A, C, B
Intervention: Active control [moxifloxacin] on Day 2 Treatment C (Drug)
Treatment Sequence 2: A, C, B
Intervention: Placebo for Balovaptan Treatment C (Drug)
Treatment Sequence 2: A, C, B
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 2: A, C, B
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 2: A, C, B
Intervention: Moxifloxacin Treatment C (Drug)
Treatment Sequence 2: A, C, B
Intervention: Placebo for Moxifloxacin Treatment C (Drug)
Treatment Sequence 3: B, A, C
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 3: B, A, C
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 3: B, A, C
Intervention: Active control [moxifloxacin] on Day 2 Treatment C (Drug)
Treatment Sequence 3: B, A, C
Intervention: Moxifloxacin Treatment C (Drug)
Treatment Sequence 3: B, A, C
Intervention: Placebo for Moxifloxacin Treatment C (Drug)
Treatment Sequence 4: B, C, A
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 4: B, C, A
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 4: B, C, A
Intervention: Active control [moxifloxacin] on Day 2 Treatment C (Drug)
Treatment Sequence 4: B, C, A
Intervention: Placebo for Balovaptan Treatment C (Drug)
Treatment Sequence 4: B, C, A
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 4: B, C, A
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 4: B, C, A
Intervention: Moxifloxacin Treatment C (Drug)
Treatment Sequence 4: B, C, A
Intervention: Placebo for Moxifloxacin Treatment C (Drug)
Treatment Sequence 5: C, A, B
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 5: C, A, B
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 5: C, A, B
Intervention: Active control [moxifloxacin] on Day 2 Treatment C (Drug)
Treatment Sequence 5: C, A, B
Intervention: Placebo for Balovaptan Treatment C (Drug)
Treatment Sequence 5: C, A, B
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 5: C, A, B
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 5: C, A, B
Intervention: Moxifloxacin Treatment C (Drug)
Treatment Sequence 5: C, A, B
Intervention: Placebo for Moxifloxacin Treatment C (Drug)
Treatment Sequence 6: C, B, A
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 6: C, B, A
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 6: C, B, A
Intervention: Active control [moxifloxacin] on Day 2 Treatment C (Drug)
Treatment Sequence 6: C, B, A
Intervention: Placebo for Balovaptan Treatment C (Drug)
Treatment Sequence 6: C, B, A
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 6: C, B, A
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 6: C, B, A
Intervention: Moxifloxacin Treatment C (Drug)
Treatment Sequence 6: C, B, A
Intervention: Placebo for Moxifloxacin Treatment C (Drug)
Treatment Sequence 7: A, B, D
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 7: A, B, D
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 7: A, B, D
Intervention: Active control [Moxifloxacin] on Day 15 Treatment D (Drug)
Treatment Sequence 7: A, B, D
Intervention: Placebo for Balovaptan Treatment D (Drug)
Treatment Sequence 7: A, B, D
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 7: A, B, D
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 7: A, B, D
Intervention: Placebo for Moxifloxacin Treatment D (Drug)
Treatment Sequence 7: A, B, D
Intervention: Moxifloxacin Treatment D (Drug)
Treatment Sequence 8: A, D, B
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 8: A, D, B
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 8: A, D, B
Intervention: Active control [Moxifloxacin] on Day 15 Treatment D (Drug)
Treatment Sequence 8: A, D, B
Intervention: Placebo for Balovaptan Treatment D (Drug)
Treatment Sequence 8: A, D, B
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 8: A, D, B
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 8: A, D, B
Intervention: Placebo for Moxifloxacin Treatment D (Drug)
Treatment Sequence 8: A, D, B
Intervention: Moxifloxacin Treatment D (Drug)
Treatment Sequence 9: B, A, D
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 9: B, A, D
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 9: B, A, D
Intervention: Active control [Moxifloxacin] on Day 15 Treatment D (Drug)
Treatment Sequence 9: B, A, D
Intervention: Placebo for Balovaptan Treatment D (Drug)
Treatment Sequence 9: B, A, D
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 9: B, A, D
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 9: B, A, D
Intervention: Placebo for Moxifloxacin Treatment D (Drug)
Treatment Sequence 9: B, A, D
Intervention: Moxifloxacin Treatment D (Drug)
Treatment Sequence 10: B, D, A
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 10: B, D, A
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 10: B, D, A
Intervention: Active control [Moxifloxacin] on Day 15 Treatment D (Drug)
Treatment Sequence 10: B, D, A
Intervention: Placebo for Balovaptan Treatment D (Drug)
Treatment Sequence 10: B, D, A
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 10: B, D, A
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 10: B, D, A
Intervention: Placebo for Moxifloxacin Treatment D (Drug)
Treatment Sequence 10: B, D, A
Intervention: Moxifloxacin Treatment D (Drug)
Treatment Sequence 11: D, A, B
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 11: D, A, B
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 11: D, A, B
Intervention: Active control [Moxifloxacin] on Day 15 Treatment D (Drug)
Treatment Sequence 11: D, A, B
Intervention: Placebo for Balovaptan Treatment D (Drug)
Treatment Sequence 11: D, A, B
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 11: D, A, B
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 11: D, A, B
Intervention: Placebo for Moxifloxacin Treatment D (Drug)
Treatment Sequence 11: D, A, B
Intervention: Moxifloxacin Treatment D (Drug)
Treatment Sequence 12: D, B, A
Intervention: Balovaptan therapeutic dose Treatment A (Drug)
Treatment Sequence 12: D, B, A
Intervention: Balovaptan supra-therapeutic dose Treatment B (Drug)
Treatment Sequence 12: D, B, A
Intervention: Active control [Moxifloxacin] on Day 15 Treatment D (Drug)
Treatment Sequence 12: D, B, A
Intervention: Placebo for Balovaptan Treatment D (Drug)
Treatment Sequence 12: D, B, A
Intervention: Placebo for Moxifloxacin Treatment A (Drug)
Treatment Sequence 12: D, B, A
Intervention: Placebo for Moxifloxacin Treatment B (Drug)
Treatment Sequence 12: D, B, A
Intervention: Placebo for Moxifloxacin Treatment D (Drug)
Treatment Sequence 12: D, B, A
Intervention: Moxifloxacin Treatment D (Drug)
Outcomes
Primary Outcomes
Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
Time Frame: 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 Outcomes
- AUC0-24 of M3 Metabolite(Day 1 and Day 14 (Each treatment period is 15 days.))
- Cmax of Balovaptan(Day 1 and Day 14. (Each treatment period is 15 days.))
- 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.))
- Number of Categorical Outliers for QTcF(Up to approximately 20 weeks)
- Number of Treatment Emergent Changes of T-Wave Morphology(Up to approximately 20 weeks)
- Cmax of M2 Metabolite(Day 1 and Day 14. (Each treatment period is 15 days.))
- 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.))
- Number of Categorical Outliers for HR(Up to approximately 20 weeks)
- 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.))
- Number of Treatment Emergent Changes of U-Wave Presence(Up to approximately 20 weeks)
- 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.))
- 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.))
- Percentage of Participants With Treatment Emergent Adverse Events(Up to approximately 20 weeks.)
- 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.))
- Number of Categorical Outliers for PR(Up to approximately 20 weeks)
- Tmax M3 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.))
- 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 Concentration for M3 From Concentration-QTc Analysis(Baseline, Day 14. (Each treatment period is 15 days.))
- 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.))
- Number of Categorical Outliers for QRS(Up to approximately 20 weeks)
- AUC0-24 of M2 Metabolite(Day 1 and 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.))