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临床试验/NCT05961397
NCT05961397
已完成
1 期

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

AstraZeneca5 个研究点 分布在 1 个国家目标入组 20 人2021年8月10日
适应症Hypertension
干预措施baxdrostat
相关药物baxdrostat

概览

阶段
1 期
干预措施
baxdrostat
疾病 / 适应症
Hypertension
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.
状态
已完成
最后更新
2年前

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.

注册库
clinicaltrials.gov
开始日期
2021年8月10日
结束日期
2022年4月15日
最后更新
2年前
研究类型
Interventional
研究设计
Parallel
性别
All

研究者

发起方
AstraZeneca
责任方
Sponsor

入排标准

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

Moderate hepatic impairment group

Subjects with a Child-Pugh score of 7 to 9 (Category B) at screening

干预措施: baxdrostat

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

研究点 (5)

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