Clinical trial NCT03764449: A Study Investigating the Absolute Oral Bioavailability of Balovaptan After Single and Multiple Daily Oral Doses of Balovaptan in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-12-05
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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 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.

Primary outcomes:
measure: Absolute Bioavailability of Oral Balovaptan at Dose Level A (Cohort 1)
timeFrame: Day 1 of Period 1 (Period 1 is 14 days).
Secondary outcomes:
measure: Absolute Bioavailability of Oral Balovaptan at Dose Level B (Cohort 2)
timeFrame: Day 1 of Period 1 (Period 1 is 14 days).
measure: Absolute Bioavailability of Oral Balovaptan at Dose A and Dose B
timeFrame: Day 14 of Period 2 (Period 2 is 19 days).
measure: Maximum Plasma Concentration (Cmax) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Cmax of Oral Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Cmax of M2 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Cmax of M3 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Time to Maximum Observed Plasma Concentration (Tmax) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Tmax of Oral Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Tmax of M2 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Tmax of M3 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Apparent Terminal Half-Life (t1/2) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: T1/2 of Oral Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: T1/2 of M2 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: T1/2 of M3 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Plasma Concentration Time Point (AUC0-last) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days)
measure: AUC0-last of Oral Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days)
measure: AUC0-last of M2 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days)
measure: AUC0-last of M3 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: AUC0-inf of Oral Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days).
measure: AUC0-inf of M2 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days).
measure: AUC0-inf of M3 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days).
measure: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUC0-24) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: AUC0-24 of Oral Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: AUC0-24 of M2 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: AUC0-24 of M3 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Last Measurable Plasma Concentration (Clast) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Clast of Oral Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Clast of M2 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Clast of M3 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Time of Last Measurable Plasma Concentration (Tlast) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Tlast of Oral Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Tlast of M2 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Tlast of M3 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Terminal Elimination Rate Constant (λz) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: λz of Oral Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: λz of M2 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: λz of M3 Metabolites
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Total Body Clearance (CL) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Volume of Distribution (Vss) of IV Balovaptan
timeFrame: Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days).
measure: Percentage of Participants With Treatment-Emergent Adverse Events
timeFrame: Up to 35 days from screening (sceening is up to 28 days prior to admission to the clinical research unit).
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Pra International Group B.V
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.