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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Oral Balovaptan
* Drug: IV Balovaptan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>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<br>* 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.<br>Drug: IV Balovaptan<br>* 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.<br>|
| Experimental: Cohort 2<br>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<br>* 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.<br>Drug: IV Balovaptan<br>* 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.<br>|

What is the study measuring?
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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). |