The Effect of Hepatic Impairment on the Pharmacokinetics of Balovaptan: A Phase I, Multiple-Center, Open-Label Study Following Multiple Daily Oral Doses of Balovaptan in Subjects With Moderate Hepatic Impairment and Healthy Subjects With Normal Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Plasma concentration of M3 metabolite
研究概览
简要总结
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%).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Reference group
Healthy pariticipants with normal hepatic function.
干预措施: Balovaptan (Drug)
Test group
Participants with moderate hepatic impairment.
干预措施: Balovaptan (Drug)
结局指标
主要结局
Plasma concentration of M3 metabolite
时间窗: 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 balovaptan
时间窗: 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
时间窗: 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 on Day 1 of balovaptan
时间窗: 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
时间窗: 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 M3 metabolite
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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 maximum observed plasma (MRcmax) of M3 metabolite
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- 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).)