A Study to Investigate the Effect of Itraconazole on the PK of Multiple 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, one-sequence, two-period within-subject study to investigate the effect of CYP3A inhibition on the PK of balovaptan in healthy male and female volunteers using itraconazole as a CYP3A inhibitor. 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 Itraconazole on the Pharmacokinetics of Multiple Doses of Balovaptan in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Balovaptan
* Drug: Itraconazole


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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Balovaptan + Itraconzole<br>Dosing in Period 1 was separated by at least a 7 day washout period before dosing starts in Period 2. Participants received the study drugs in 2 periods over a total of 37 days. | Drug: Balovaptan<br>* In Period 1, balovaptan was administered orally once daily (qd) on Days 1 to 10. In Period 2, balovaptan was administered qd on Days 6 to 20.<br>Drug: Itraconazole<br>* In Period 2, 200 mg itraconzole was administered bid for 4 days and qd on Days 5-20, approximately 12 hours apart. On Days 6-20, 200 mg itraconazole was administered qd.<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, Day 10 and Day 15 of Period 2 | 
| Maximum Plasma Concentration (Cmax) for M2 Metabolite (as Applicable) | Cmax is the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. | Day 10 of Period 1, Day 10 and Day 15 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, Day 10 and Day 15 of Period 2 | 
| Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for Balovaptan |  | Day 10 of Period 1, Day 10 and Day 15 of Period 2 | 
| Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M2 Metabolite (as Applicable) |  | Day 10 of Period 1, Day 10 and Day 15 of Period 2 | 
| Area Under the Concentration Vs Time Curve Over the Dosing Interval (AUC0-tau) for M3 Metabolite |  | Day 10 of Period 1, Day 10 and Day 15 of Period 2 | 
| Time to Maximum Observed Plasma Concentration (Tmax) for Balovaptan |  | Day 10 of Period 1; Day 10 and Day 15 of Period 2 | 
| Time to Maximum Observed Plasma Concentration (Tmax) for M2 Metabolite (as Applicable) |  | Day 10 of Period 1; Day 10 and Day 15 of Period 2 | 
| Time to Maximum Observed Plasma Concentration (Tmax) for M3 Metabolite |  | Day 10 of Period 1; Day 10 and Day 15 of Period 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Plasma Concentration (Ctrough) for Balovaptan |  | Day 10 of Period 1; Day 10 and Day 15 of Period 2 | 
| Trough Plasma Concentration (Ctrough) for M2 Metabolite (as Applicable) |  | Day 10 of Period 1; Day 10 and Day 15 of Period 2 | 
| Trough Plasma Concentration (Ctrough) for M3 Metabolite |  | Day 10 of Period 1; Day 10 and Day 15 of Period 2 | 
| Time to Steady State for Balovaptan |  | Days 1, 3, 5, 8, 9, 10 in Period 1 and Days 1, 3, 5, 8, 9, 10, 13, 14, 15 in Period 2 | 
| Percentage of Participants With Adverse Events |  | Up to 21 days postdose |