Study to Investigate the Effect of Balovaptan on the QTC Interval in Healthy Subjects
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Drug: Active control [moxifloxacin] on Day 2 Treatment CDrug: Active control [Moxifloxacin] on Day 15 Treatment DDrug: Placebo for Moxifloxacin Treatment ADrug: Placebo for Moxifloxacin Treatment BDrug: Placebo for Moxifloxacin Treatment DDrug: Placebo for Moxifloxacin Treatment C
- Registration Number
- NCT03808298
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 57
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence 6: C, B, A Balovaptan therapeutic dose Treatment A - Treatment Sequence 2: A, C, B Balovaptan therapeutic dose Treatment A - Treatment Sequence 4: B, C, A Balovaptan therapeutic dose Treatment A - Treatment Sequence 5: C, A, B Balovaptan therapeutic dose Treatment A - Treatment Sequence 8: A, D, B Balovaptan therapeutic dose Treatment A - Treatment Sequence 9: B, A, D Balovaptan therapeutic dose Treatment A - Treatment Sequence 11: D, A, B Balovaptan therapeutic dose Treatment A - Treatment Sequence 12: D, B, A Balovaptan therapeutic dose Treatment A - Treatment Sequence 5: C, A, B Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 2: A, C, B Moxifloxacin Treatment C - Treatment Sequence 1: A, B, C Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 8: A, D, B Moxifloxacin Treatment D - Treatment Sequence 4: B, C, A Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 6: C, B, A Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 7: A, B, D Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 8: A, D, B Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 9: B, A, D Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 10: B, D, A Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 5: C, A, B Moxifloxacin Treatment C - Treatment Sequence 12: D, B, A Moxifloxacin Treatment D - Treatment Sequence 1: A, B, C Moxifloxacin Treatment C - Treatment Sequence 6: C, B, A Moxifloxacin Treatment C - Treatment Sequence 1: A, B, C Balovaptan therapeutic dose Treatment A - Treatment Sequence 1: A, B, C Placebo for Moxifloxacin Treatment C - Treatment Sequence 2: A, C, B Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 2: A, C, B Placebo for Balovaptan Treatment C - Treatment Sequence 3: B, A, C Placebo for Moxifloxacin Treatment A - Treatment Sequence 3: B, A, C Moxifloxacin Treatment C - Treatment Sequence 4: B, C, A Placebo for Balovaptan Treatment C - Treatment Sequence 4: B, C, A Placebo for Moxifloxacin Treatment B - Treatment Sequence 4: B, C, A Placebo for Moxifloxacin Treatment C - Treatment Sequence 6: C, B, A Placebo for Moxifloxacin Treatment B - Treatment Sequence 1: A, B, C Placebo for Balovaptan Treatment C - Treatment Sequence 1: A, B, C Placebo for Moxifloxacin Treatment A - Treatment Sequence 1: A, B, C Placebo for Moxifloxacin Treatment B - Treatment Sequence 2: A, C, B Placebo for Moxifloxacin Treatment C - Treatment Sequence 3: B, A, C Balovaptan therapeutic dose Treatment A - Treatment Sequence 3: B, A, C Active control [moxifloxacin] on Day 2 Treatment C - Treatment Sequence 3: B, A, C Placebo for Moxifloxacin Treatment C - Treatment Sequence 4: B, C, A Active control [moxifloxacin] on Day 2 Treatment C - Treatment Sequence 11: D, A, B Placebo for Moxifloxacin Treatment A - Treatment Sequence 1: A, B, C Active control [moxifloxacin] on Day 2 Treatment C - Treatment Sequence 2: A, C, B Active control [moxifloxacin] on Day 2 Treatment C - Treatment Sequence 3: B, A, C Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 4: B, C, A Placebo for Moxifloxacin Treatment A - Treatment Sequence 5: C, A, B Placebo for Moxifloxacin Treatment A - Treatment Sequence 6: C, B, A Placebo for Moxifloxacin Treatment A - Treatment Sequence 6: C, B, A Placebo for Moxifloxacin Treatment C - Treatment Sequence 7: A, B, D Active control [Moxifloxacin] on Day 15 Treatment D - Treatment Sequence 7: A, B, D Placebo for Moxifloxacin Treatment A - Treatment Sequence 8: A, D, B Placebo for Moxifloxacin Treatment A - Treatment Sequence 9: B, A, D Active control [Moxifloxacin] on Day 15 Treatment D - Treatment Sequence 10: B, D, A Placebo for Moxifloxacin Treatment B - Treatment Sequence 11: D, A, B Active control [Moxifloxacin] on Day 15 Treatment D - Treatment Sequence 11: D, A, B Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 11: D, A, B Moxifloxacin Treatment D - Treatment Sequence 2: A, C, B Placebo for Moxifloxacin Treatment B - Treatment Sequence 4: B, C, A Moxifloxacin Treatment C - Treatment Sequence 5: C, A, B Placebo for Balovaptan Treatment C - Treatment Sequence 5: C, A, B Placebo for Moxifloxacin Treatment C - Treatment Sequence 6: C, B, A Placebo for Balovaptan Treatment C - Treatment Sequence 7: A, B, D Placebo for Balovaptan Treatment D - Treatment Sequence 10: B, D, A Active control [Moxifloxacin] on Day 15 Treatment D - Treatment Sequence 12: D, B, A Balovaptan supra-therapeutic dose Treatment B - Treatment Sequence 2: A, C, B Placebo for Moxifloxacin Treatment A - Treatment Sequence 3: B, A, C Placebo for Balovaptan Treatment C - Treatment Sequence 3: B, A, C Placebo for Moxifloxacin Treatment B - Treatment Sequence 6: C, B, A Active control [moxifloxacin] on Day 2 Treatment C - Treatment Sequence 7: A, B, D Placebo for Moxifloxacin Treatment B - Treatment Sequence 9: B, A, D Placebo for Moxifloxacin Treatment B - Treatment Sequence 9: B, A, D Placebo for Moxifloxacin Treatment D - Treatment Sequence 10: B, D, A Placebo for Moxifloxacin Treatment A - Treatment Sequence 10: B, D, A Placebo for Moxifloxacin Treatment D - Treatment Sequence 10: B, D, A Moxifloxacin Treatment D - Treatment Sequence 11: D, A, B Placebo for Balovaptan Treatment D - Treatment Sequence 11: D, A, B Placebo for Moxifloxacin Treatment D - Treatment Sequence 12: D, B, A Placebo for Balovaptan Treatment D - Treatment Sequence 5: C, A, B Active control [moxifloxacin] on Day 2 Treatment C - Treatment Sequence 5: C, A, B Placebo for Moxifloxacin Treatment B - Treatment Sequence 7: A, B, D Placebo for Moxifloxacin Treatment D - Treatment Sequence 7: A, B, D Moxifloxacin Treatment D - Treatment Sequence 8: A, D, B Active control [Moxifloxacin] on Day 15 Treatment D - Treatment Sequence 8: A, D, B Placebo for Moxifloxacin Treatment B - Treatment Sequence 9: B, A, D Placebo for Balovaptan Treatment D - Treatment Sequence 10: B, D, A Balovaptan therapeutic dose Treatment A - Treatment Sequence 12: D, B, A Placebo for Moxifloxacin Treatment D - Treatment Sequence 7: A, B, D Balovaptan therapeutic dose Treatment A - Treatment Sequence 8: A, D, B Placebo for Balovaptan Treatment D - Treatment Sequence 8: A, D, B Placebo for Moxifloxacin Treatment D - Treatment Sequence 9: B, A, D Placebo for Moxifloxacin Treatment A - Treatment Sequence 9: B, A, D Moxifloxacin Treatment D - Treatment Sequence 10: B, D, A Placebo for Balovaptan Treatment D - Treatment Sequence 11: D, A, B Placebo for Moxifloxacin Treatment B - Treatment Sequence 12: D, B, A Placebo for Moxifloxacin Treatment A - Treatment Sequence 12: D, B, A Placebo for Moxifloxacin Treatment B - Treatment Sequence 12: D, B, A Active control [Moxifloxacin] on Day 15 Treatment D -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Cmax 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.) 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.) 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 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 (-).
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.
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.
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.) 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.
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.
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.) 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.
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.
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.) 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.
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.
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.)
Trial Locations
- Locations (1)
PRA International Clinical Pharmacology Center (EDS US Clinic)
🇺🇸Lenexa, Kansas, United States