The Effect of Hepatic Impairment on the Pharmacokinetics of Balovaptan
- Registration Number
- NCT03912350
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a multi-center, non-randomized, open-label, parallel group, multiple-dose study to assess the pharmacokinetic, safety, and tolerability of balovaptan in male and female subjects with moderate hepatic impairment compared to healthy subjects with normal hepatic function matched by age (±10 years), sex, and body mass index (BMI; ±20%).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Reference group Balovaptan Healthy pariticipants with normal hepatic function. Test group Balovaptan Participants with moderate hepatic impairment.
- Primary Outcome Measures
Name Time Method AUC during the dosing interval on Day 1 of balovaptan Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1 AUC during the dosing interval on Day 1 of M2 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1 Metabolite:Parent ratio of maximum observed plasma (MRcmax) of M3 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Plasma concentration of balovaptan Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16 hours post-dose on Day 1; pre-dose on Day 2 to Day 13; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Plasma concentration of M2 metabolite, as applicable Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16 hours post-dose on Day 1; pre-dose on Day 2 to Day 13; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Plasma concentration of M3 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16 hours post-dose on Day 1; pre-dose on Day 2 to Day 13; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 AUC during the dosing interval at steady state on Day 14 of M3 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 AUC during the dosing interval on Day 1 of M3 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1 AUC during the dosing interval at steady state on Day 14 of balovaptan Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 AUC during the dosing interval at steady state on Day 14 of M2 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Maximum observed plasma concentration (Cmax) of balovaptan 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Maximum observed plasma concentration (Cmax) of M2 metabolite 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Metabolite:Parent ratio of maximum observed plasma (MRcmax) of M2 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent volume of distribution (V/F) of balovaptan Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent volume of distribution (V/F) of M2 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent volume of distribution (V/F) of M3 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Maximum observed plasma concentration (Cmax) of M3 metabolite 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Time of maximum observed plasma concentration (Tmax) of balovaptan 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Time of maximum observed plasma concentration (Tmax) of M2 metabolite 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Time of maximum observed plasma concentration (Tmax) of M3 metabolite 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Metabolite:Parent ratio of area under the plasma (MRauc) of M2 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Metabolite:Parent ratio of area under the plasma (MRauc) of M3 metabolite Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Terminal phase rate constant (λZ) of balovaptan, when possible Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Terminal phase rate constant (λZ) of M2 metabolite, when possible Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Terminal phase rate constant (λZ) of M3 metabolite, when possible Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent terminal elimination half-life (t½) of balovaptan, when possible Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent terminal elimination half-life (t½) of M2 metabolite, when possible Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent terminal elimination half-life (t½) of M3 metabolite, when possible Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent plasma clearance after oral administration (CLss/F) of balovaptan, when possible Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent plasma clearance after oral administration (CLss/F) of M2 metabolite, when possible Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent volume of distribution based on the terminal phase after oral administration (Vz/F) of M2 metabolite, when possible 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent plasma clearance after oral administration (CLss/F) of M3 metabolite, when possible Pre-dose, and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent volume of distribution based on the terminal phase after oral administration (Vz/F) of balovaptan, when possible 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14 Apparent volume of distribution based on the terminal phase after oral administration (Vz/F) of M3 metabolite, when possible 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 1; pre-dose and 1, 2, 3, 4, 5, 6, 9, 12, 16, and 24 hours post-dose on Day 14
- Secondary Outcome Measures
Name Time Method Percentage of participants with adverse events Up to approximately 18 weeks from screening (screening is up to 28 days prior to admission to the clinical research unit).