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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Oral Balovaptan; Drug: IV Balovaptan

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • Pra International Group B.V

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants received the study drug at dose level A in 2 periods. There was a minimum of a 14-day wash out period between Day 1 of Period 1 and Day 1 of Period 2.	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.; Drug: 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.
Experimental: Cohort 2; Participants received the study drug at dose level B in 2 periods. There was a minimum of a 14-day wash out period between Day 1 of Period 1 and Day 1 of Period 2.	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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).
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).
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).
Cmax of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Cmax of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Cmax of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
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).
Tmax of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Tmax of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Tmax of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
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).
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).
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).
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).
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)
AUC0-last of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days)
AUC0-last of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days)
AUC0-last of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days)
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).
AUC0-inf of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days).
AUC0-inf of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days).
AUC0-inf of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days).
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).
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).
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).
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).
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).
Clast of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Clast of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Clast of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
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).
Tlast of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Tlast of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Tlast of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
Terminal Elimination Rate Constant (λz) of IV Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
λz of Oral Balovaptan		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
λz of M2 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
λz of M3 Metabolites		Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
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).
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).
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).

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Derks M, Lennon-Chrimes S, Guenther A, Squassante L, Wandel C, Szczesny P, Paehler A, Kletzl H. Bioavailability and pharmacokinetic profile of balovaptan, a selective, brain-penetrant vasopressin 1a receptor antagonist, in healthy volunteers. Expert Opin Investig Drugs. 2021 Aug;30(8):893-901. doi: 10.1080/13543784.2021.1948009. Epub 2021 Jul 16.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2019
• Primary Completion (Actual): March 4, 2019
• Study Completion (Actual): March 15, 2019

Study Registration Dates

• First Submitted: November 30, 2018
• First Submitted That Met QC Criteria: December 3, 2018
• First Posted (Actual): December 5, 2018

Study Record Updates

• Last Update Posted (Actual): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: WP40607

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No