A Phase 1, Open-label, Single-dose, Parallel-group Study to Evaluate the Pharmacokinetics of CIN-107 in Subjects With Varying Degrees of Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 20
- 试验地点
- 5
- 主要终点
- Maximum Plasma Concentration [Cmax] of baxdrostat and the CIN-107-M metabolite following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
研究概览
简要总结
The goal of this Phase 1, open-label, single-dose, parallel-group study is to evaluate the pharmacokinetics (PK) of a single 10-mg oral dose of baxdrostat in subjects with varying degrees of hepatic function. The main objectives are to:
- To assess the safety and tolerability of baxdrostat following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function; and
- To characterize the PK of baxdrostat following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
Participants were administered a single 10-mg oral dose of baxdrostat in the fasted state the morning of Day 1. Plasma samples were drawn at various timepoints. Safety assessments included adverse events, vital signs, 12-lead electrocardiograms (ECGs), clinical laboratory evaluations, and physical examinations.
Twenty subjects in 2 groups based on the Child-Pugh classification in the protocol at screening: up to 10 subjects in the normal hepatic function group and up to 10 subjects in the moderate hepatic impairment group. Twenty subjects entered and completed the study.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Is between the ages of 18 and 80 years, inclusive, and in stable health condition. (For hepatically impaired subjects, their hepatic function category must be stable for a minimum of 3 months prior to screening.)
- •Is a non-nicotine user or smokes =<10 cigarettes/day;
- •Has a BMI between 18 and 42 kg/m2, inclusive;
- •Is able to understand and willing to comply with study procedures and restrictions and provide written informed consent;
- •if a male subject with a female partner of childbearing potential must agree to use 2 medically accepted, highly effective methods of birth control for 90 days.
- •if male, must agree to abstain from sperm donation for 90 days; and
- •if female with a male partner, must be surgically sterile, postmenopausal, or agree to use 2 medically accepted, highly effective methods of birth control from Day -14 until 60 days after study drug dosing
排除标准
- •Personal or family history of long QT syndrome, torsades de pointes, or other complex ventricular arrhythmias, or family history of sudden death;
- •History of, or current, clinically significant arrhythmias;
- •Prolonged QTcF (>460 msec) based on the average of triplicate ECGs;
- •Estimated glomerular filtration rate (or creatinine clearance) <50 mL/min/1.73 m2;
- •Evidence of any of the following: Encephalopathy grade 2 or worse, Seated systolic BP >160 mmHg and/or diastolic BP >100 mmHg, or systolic BP <90 mmHg and/or diastolic BP <50 mmHg, resting heart rate >100 beats per minute (bpm) or <50 bpm, Oral temperature >37.6°C (>99.68°F), Respiration rate <12 or >20 breaths per minute, symptomatic postural tachycardia or orthostatic hypotension, abnormal serum potassium >upper limit of normal range, abnormal serum sodium <130 mEq/L, positive test for HIV antibody, hepatitis C , hepatitis B , or SARS-CoV-2 RNA
- •Current treatment with weight loss medication or prior weight loss surgery;
- •Use of a moderate or strong inhibitor of CYP3A4 within 14 days prior to the dose of study drug OR use of a moderate or strong inducer of CYP3A4 within 28 days prior to the dose of study drug;
- •Corticosteroid use (systemic or extensive topical use) within 3 months prior to study drug dosing
- •Pregnant, breastfeeding, or planning to become pregnant during the study
研究组 & 干预措施
Normal hepatic function group
Subjects with normal hepatic function
干预措施: baxdrostat (Drug)
Moderate hepatic impairment group
Subjects with a Child-Pugh score of 7 to 9 (Category B) at screening
干预措施: baxdrostat (Drug)
结局指标
主要结局
Maximum Plasma Concentration [Cmax] of baxdrostat and the CIN-107-M metabolite following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
时间窗: up to 72 hours post-dose
Cmax will be determined for baxdrostat and the CIN-107M metabolite
Area under the curve (AUC) for baxdrostat and the CIN-107-M metabolite following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function
时间窗: up to 72 hours post-dose
Measurement of plasma concentrations of baxdrostat and its major metabolite CIN-107-M. AUC \[0 to 24 hours, 0 to last quantifiable concentration, and 0 to infinity of baxdrostat\] will be determined for baxdrostat and the CIN-107M metabolite.
Time to Maximum Plasma Concentration [Tmax] of baxdrostat and the CIN-107-M metabolite following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
时间窗: up to 72 hours post-dose
Tmax will be determined for baxdrostat and the CIN-107M metabolite
Incidence of treatment emergent adverse events following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
时间窗: up to 72 hours post-dose
The safety and tolerability of baxdrostat was assessed throughout the study based on incidence of treatment emergent adverse events (AEs), following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
Terminal elimination half-life of baxdrostat and the CIN-107-M metabolite following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
时间窗: up to 72 hours post-dose
Terminal elimination half-life will be determined for baxdrostat and the CIN-107M metabolite
次要结局
未报告次要终点