Clinical trial NCT03808298: Study to Investigate the Effect of Balovaptan on the QTC Interval in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-01-17
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
timeFrame: Baseline (Predose Day 1), Day 14. (Each treatment period is 15 days.)
Secondary outcomes:
measure: Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings
timeFrame: Baseline (Predose Day 1), Day 1. (Each treatment period is 15 days.)
measure: Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings
timeFrame: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
measure: Change-From-Baseline Heart Rate Measured on 12-Lead ECGs Extracted From Continuous Recordings
timeFrame: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
measure: Change-From-Baseline PR Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
timeFrame: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
measure: Change-From-Baseline QRS Interval Measured on 12-Lead ECGs Extracted From Continuous Recordings
timeFrame: Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
measure: Number of Categorical Outliers for QTcF
timeFrame: Up to approximately 20 weeks
measure: Number of Categorical Outliers for HR
timeFrame: Up to approximately 20 weeks
measure: Number of Categorical Outliers for PR
timeFrame: Up to approximately 20 weeks
measure: Number of Categorical Outliers for QRS
timeFrame: Up to approximately 20 weeks
measure: Number of Treatment Emergent Changes of T-Wave Morphology
timeFrame: Up to approximately 20 weeks
measure: Number of Treatment Emergent Changes of U-Wave Presence
timeFrame: Up to approximately 20 weeks
measure: Tmax of Balovaptan
timeFrame: Day 1 and Day 14. (Each treatment period is 15 days.)
measure: Tmax of M2 Metabolite
timeFrame: Day 1 and Day 14. (Each treatment period is 15 days.)
measure: Tmax M3 Metabolite
timeFrame: Day 1 and Day 14. (Each treatment period is 15 days.)
measure: Cmax of Balovaptan
timeFrame: Day 1 and Day 14. (Each treatment period is 15 days.)
measure: Cmax of M2 Metabolite
timeFrame: Day 1 and Day 14. (Each treatment period is 15 days.)
measure: Cmax of M3 Metabolite
timeFrame: Day 1 and Day 14. (Each treatment period is 15 days.)
measure: AUC0-24 of Balovaptan
timeFrame: Day 1 and Day 14 (Each treatment period is 15 days.)
measure: AUC0-24 of M2 Metabolite
timeFrame: Day 1 and Day 14 (Each treatment period is 15 days.)
measure: AUC0-24 of M3 Metabolite
timeFrame: Day 1 and Day 14 (Each treatment period is 15 days.)
measure: Tmax of Moxifloxacin
timeFrame: Days 2 (Treatment C) or 15 (Treatment D). (Each treatment period is 15 days.)
measure: Cmax of Moxifloxacin
timeFrame: Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.)
measure: AUC0-24 of Moxifloxacin
timeFrame: Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.)
measure: Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of Balovaptan From Concentration-QTc Analysis
timeFrame: Baseline, Day 14. (Each treatment period is 15 days.)
measure: Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentrations at Tmax of M2 From Concentration-QTc Analysis
timeFrame: Baseline, Day 14. (Each treatment period is 15 days.)
measure: Predicted ΔΔQTcF Interval at Geometric Mean Peak Concentration for M3 From Concentration-QTc Analysis
timeFrame: Baseline, Day 14. (Each treatment period is 15 days.)
measure: Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records
timeFrame: Baseline, Day 15. (Each treatment period is 15 days.)
measure: Percentage of Participants With Treatment Emergent Adverse Events
timeFrame: Up to approximately 20 weeks.
Other outcomes:
Locations:
city: Lenexa
country: United States
facility: PRA International Clinical Pharmacology Center (EDS US Clinic)
state: Kansas
Study officials:
References: