A Study Investigating the Absolute Oral Bioavailability of Balovaptan After Single and Multiple Daily Oral Doses of Balovaptan in Healthy Volunteers
- Registration Number
- NCT03764449
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 IV Balovaptan 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. Cohort 2 IV Balovaptan 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. Cohort 1 Oral Balovaptan 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. Cohort 2 Oral Balovaptan 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.
- Primary Outcome Measures
Name Time Method Absolute Bioavailability of Oral Balovaptan at Dose Level A (Cohort 1) Day 1 of Period 1 (Period 1 is 14 days). Absolute oral bioavailability of a single dose A of balovaptan.
- Secondary Outcome Measures
Name Time Method Tmax of M3 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) 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). 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). AUC0-last of M2 Metabolites 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). 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 M3 Metabolites 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 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 M3 Metabolites 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). 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). 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 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). Absolute Bioavailability of Oral Balovaptan at Dose Level B (Cohort 2) Day 1 of Period 1 (Period 1 is 14 days). Absolute oral bioavailability of a single dose B balovaptan.
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 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 M2 Metabolites Day 1 of Period 1 (Period 1 is 14 days); Day 14 of Period 2 (Period 2 is 19 days). AUC0-last of Oral Balovaptan Day 1 of Period 1 (Period 1 is 14 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). 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). Absolute Bioavailability of Oral Balovaptan at Dose A and Dose B Day 14 of Period 2 (Period 2 is 19 days). Absolute oral bioavailability of balovaptan after once daily doses of Dose A and Dose B for 14 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). Tmax of Oral Balovaptan 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). Tlast of M2 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). 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). Tlast of Oral 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).
Trial Locations
- Locations (1)
Pra International Group B.V
🇳🇱Groningen, Netherlands