Study to Investigate the Effect of Balovaptan on the QTC Interval in Healthy Subjects

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03808298
• Other study ID #: WP40734
• Status: Completed
• Phase: Phase 1
• Start date: February 7, 2019
• Est. completion date: July 13, 2019

Study information

• Verified date: July 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: July 13, 2019
• Est. primary completion date: June 14, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Balovaptan therapeutic dose Treatment A
Days 1-14: A single once daily dose at dose level A of balovaptan for 14 days
• Balovaptan supra-therapeutic dose Treatment B
Days 1-14: A single once daily oral dose at dose level B of balovaptan for 14 days.
• Active control [moxifloxacin] on Day 2 Treatment C
Day 2: A single oral dose of 400 mg moxifloxacin capsule.
• Active control [Moxifloxacin] on Day 15 Treatment D
Day 15: A single oral dose of 400 mg moxifloxacin capsule.
• Placebo for Balovaptan Treatment C
Days 1-14: Matching placebo for balovaptan for 14 days.
• Placebo for Balovaptan Treatment D
Days 1-14: Matching placebo for balovaptan for 14 days.
• Placebo for Moxifloxacin Treatment A
Day 2 and 15: A single oral dose of a matching placebo capsule for moxifloxacin.
• Placebo for Moxifloxacin Treatment B
Days 2 and 15: Single oral dose of a matching placebo capsule of moxifloxacin.
• Moxifloxacin Treatment C
Day 2: A single oral dose of 400 mg moxifloxacin capsule.
• Placebo for Moxifloxacin Treatment C
Day 15: A single oral dose of a matching placebo capsule for moxifloxacin.
• Placebo for Moxifloxacin Treatment D
Day 2: A single oral dose of a matching placebo capsule for moxifloxacin.
• Moxifloxacin Treatment D
Day 15: A single oral dose of 400 mg moxifloxacin capsule.

Locations

Country	Name	City	State
United States	PRA International Clinical Pharmacology Center (EDS US Clinic)	Lenexa	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings	Change-from-baseline QTcF (??QTcF) at dose level B of balovaptan measured on 12-lead ECGs extracted from continuous recordings at the specified time points on Day 14.	Baseline (Predose Day 1), Day 14. (Each treatment period is 15 days.)
Secondary	Change-From-Baseline QTcF at Dose Level B Measured on 12-Lead ECGs Extracted From Continuous Recordings	Change-from-baseline QTcF (??QTcF) at dose level B of balovaptan measured on 12-lead ECGs extracted from continuous recordings at the specified time points on Day 1.	Baseline (Predose Day 1), Day 1. (Each treatment period is 15 days.)
Secondary	Change-From-Baseline QTcF of Balovaptan at Dose Level A Measurred on 12-Lead ECGs Extracted From Continuous Recordings	Change-from-baseline QTcF (??QTcF) 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.	Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
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.	Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
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.	Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
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.	Baseline (Predose Day 1), Day 1 and Day 14. (Each treatment period is 15 days.)
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.	Up to approximately 20 weeks
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.	Up to approximately 20 weeks
Secondary	Number of Categorical Outliers for PR	PR outliers criteria is as an increase of PR from baseline >25% resulting in PR >200 ms.	Up to approximately 20 weeks
Secondary	Number of Categorical Outliers for QRS	QRS outlier criteria is an increase of QRS from baseline >25% resulting in QRS >120 ms.	Up to approximately 20 weeks
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 (-).	Up to approximately 20 weeks
Secondary	Number of Treatment Emergent Changes of U-Wave Presence	Number (percentage) of participants with treatment emergent changes of U-wave presence.	Up to approximately 20 weeks
Secondary	Tmax of Balovaptan		Day 1 and Day 14. (Each treatment period is 15 days.)
Secondary	Tmax of M2 Metabolite		Day 1 and Day 14. (Each treatment period is 15 days.)
Secondary	Tmax M3 Metabolite		Day 1 and Day 14. (Each treatment period is 15 days.)
Secondary	Cmax of Balovaptan		Day 1 and Day 14. (Each treatment period is 15 days.)
Secondary	Cmax of M2 Metabolite		Day 1 and Day 14. (Each treatment period is 15 days.)
Secondary	Cmax of M3 Metabolite		Day 1 and Day 14. (Each treatment period is 15 days.)
Secondary	AUC0-24 of Balovaptan		Day 1 and Day 14 (Each treatment period is 15 days.)
Secondary	AUC0-24 of M2 Metabolite		Day 1 and Day 14 (Each treatment period is 15 days.)
Secondary	AUC0-24 of M3 Metabolite		Day 1 and Day 14 (Each treatment period is 15 days.)
Secondary	Tmax of Moxifloxacin		Days 2 (Treatment C) or 15 (Treatment D). (Each treatment period is 15 days.)
Secondary	Cmax of Moxifloxacin		Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.)
Secondary	AUC0-24 of Moxifloxacin		Days 2 (Treatment C) or 15 (Treatment D) (Each treatment period is 15 days.)
Secondary	Predicted ??QTcF Interval at Geometric Mean Peak Concentrations at Tmax of Balovaptan From Concentration-QTc Analysis		Baseline, Day 14. (Each treatment period is 15 days.)
Secondary	Predicted ??QTcF Interval at Geometric Mean Peak Concentrations at Tmax of M2 From Concentration-QTc Analysis		Baseline, Day 14. (Each treatment period is 15 days.)
Secondary	Predicted ??QTcF Interval at Geometric Mean Peak Concentration for M3 From Concentration-QTc Analysis		Baseline, Day 14. (Each treatment period is 15 days.)
Secondary	Change-From-Baseline QTcF Measured on 12 Lead ECGs Extracted From Continuous Records		Baseline, Day 15. (Each treatment period is 15 days.)
Secondary	Percentage of Participants With Treatment Emergent Adverse Events		Up to approximately 20 weeks.