A Study to Investigate the Effect of Rifampicin on the PK of Multiple Doses of Balovaptin In Healthy Volunteers

Study Overview
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Brief Summary
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This study was a single-center, non-randomized, open-label, one-sequence, two-period, within-subject study to investigate the effects of multiple doses of rifampicin on the PK and safety of multiple doses of balovaptan in healthy subjects. The study was conducted at 1 site in the Netherlands.

Official Title
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A Single-Center, Non-Randomized, Open-Label, One-Sequence, Two-Period Within-Subject Study to Investigate the Effect of Rifampicin on the Pharmacokinetics of Multiple Doses of Balovaptin In Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Balovaptan
* Drug: Rifampicin


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. Rifampicin-related Exclusion Criteria: Subjects diagnosed, or suspected of having porphyria, and subjects with first-degree relatives diagnosed, or suspected of having porphyria. Known hypersensitivity to rifampicin

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: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Balovaptan + Rifampicin<br>Participants received the study drugs in 2 periods. There was a minimum of a 14-day to a maximum of a 21-day washout between the last dose in Period 1 and the first dose in Period 2. | Drug: Balovaptan<br>* In Period 1, balovaptan was administered alone as a once daily (qd) dose on Days 1 to 10. In Period 2, balovaptan was administered as a qd dose on Days 7 to 16.<br>Drug: Rifampicin<br>* In Period 2, 600 mg of rifampicin will be administered alone as a qd dose from Day 1 to Day 6, and as a qd dose on Days 7 to 16.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) for Balovaptan | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | Day 10 of Period 1 and Day 16 of Period 2 | 
| Maximum Plasma Concentration (Cmax) for M2 Metabolite | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | Day 10 of Period 1 and Day 16 of Period 2 | 
| Maximum Plasma Concentration (Cmax) for M3 Metabolite | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | Day 10 of Period 1 and Day 16 of Period 2 | 
| Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC0-24) for Balovaptan | AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose. | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 | 
| Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M2 Metabolite | AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose. | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 | 
| Area Under the Plasma Concentration Curve From Time 0 to 24 Hours for M3 Metabolite | AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post dose. | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events |  | Up to 21 days postdose | 
| Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan | Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. | Day 10 of Period 1 and Day 16 of Period 2 | 
| Time to Maximum Observed Plasma Concentration for M2 Metabolite | Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. | Day 10 of Period 1 and Day 16 of Period 2 | 
| Time to Maximum Observed Plasma Concentration for M3 Metabolite | Tmax is the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. | Day 10 of Period 1 and Day 16 of Period 2 | 
| Metabolite to Parent Ratio for M2 Metabolite Based on AUC0-24 |  | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 | 
| Metabolite to Parent Ratio for M2 Metabolite Based on Cmax |  | Day 10 of Period 1 and Day 16 of Period 2 | 
| Metabolite to Parent Ratio for M3 Metabolite Based on AUC0-24 |  | Day 10 and 11 of Period 1; Day 16 and 17 of Period 2 | 
| Metabolite to Parent Ratio for M3 Metabolite Based on Cmax |  | Day 10 of Period 1 and Day 16 of Period 2 |