A Study Investigating the Absolute Oral Bioavailability of Balovaptan After Single and Multiple Daily Oral Doses of Balovaptan in Healthy Volunteers

Healthy Volunteers Clinical Trial

Official title:

A Single-Center, Non-Randomized, Open-Label, Parallel Group, Two-Treatment Study Investigating the Absolute Oral Bioavailability of Balovaptan After Single and Multiple Daily Oral Doses of Balovaptan in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03764449
• Other study ID #: WP40607
• Status: Completed
• Phase: Phase 1
• Start date: January 10, 2019
• Est. completion date: March 15, 2019

Study information

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

Clinical Trial Summary

This study was a non-randomized, open-label, parallel group, two-treatment study in healthy volunteers to investigate the absolute oral bioavailability of balovaptan. The study was conducted at 1 site in the Netherlands.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 15, 2019
• Est. primary completion date: March 4, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 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 2 acceptable contraceptive methods during the treatment period and for 90 days after the last dose of study drug.

• For men: agreement to use contraceptive measures, and agreement to refrain from donating sperm until 90 days after the last dose of study drug.

Exclusion Criteria:

• Female subjects who are pregnant or lactating.

• 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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Oral Balovaptan
In Period 1, balovaptan was administered as a single oral dose. In Period 2, balovaptan was administered as an oral dose once daily on Day 1 to Day 14.
• IV Balovaptan
In Period 1, IV infusion of balovaptan was administered after the balovaptan oral dose. In Period 2, IV infusion of balovaptan was administered after the final oral dose of balovaptan.

Locations

Country	Name	City	State
Netherlands	Pra International Group B.V	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Bioavailability of Oral Balovaptan at Dose Level A (Cohort 1)	Absolute oral bioavailability of a single dose A of balovaptan.	Day 1 of Period 1 (Period 1 is 14 days).
Secondary	Absolute Bioavailability of Oral Balovaptan at Dose Level B (Cohort 2)	Absolute oral bioavailability of a single dose B balovaptan.	Day 1 of Period 1 (Period 1 is 14 days).
Secondary	Absolute Bioavailability of Oral Balovaptan at Dose A and Dose B	Absolute oral bioavailability of balovaptan after once daily doses of Dose A and Dose B for 14 days.	Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Maximum Plasma Concentration (Cmax) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Cmax of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Cmax of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Cmax of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Tmax of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Tmax of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Tmax of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Apparent Terminal Half-Life (t1/2) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	T1/2 of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	T1/2 of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	T1/2 of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Plasma Concentration Time Point (AUC0-last) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days)
Secondary	AUC0-last of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days)
Secondary	AUC0-last of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days)
Secondary	AUC0-last of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days)
Secondary	Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	AUC0-inf of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days).
Secondary	AUC0-inf of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days).
Secondary	AUC0-inf of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days).
Secondary	Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-24) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	AUC0-24 of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	AUC0-24 of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	AUC0-24 of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Last Measurable Plasma Concentration (Clast) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Clast of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Clast of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Clast of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Time of Last Measurable Plasma Concentration (Tlast) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Tlast of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Tlast of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Tlast of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Terminal Elimination Rate Constant (?z) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	?z of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	?z of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	?z of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Total Body Clearance (CL) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Volume of Distribution (Vss) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Secondary	Percentage of Participants With Treatment-Emergent Adverse Events		Up to 35 days from screening (sceening is up to 28 days prior to admission to the clinical research unit).