A Randomized, Double-Blind Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CIN-107 Following Multiple Oral Doses in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Fraction of the dose excreted renally (fe)
研究概览
简要总结
This is a randomized, double-blind, study to assess the safety, tolerability, PK, and PD of multiple oral doses of CIN-107 when administered to healthy adult subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects between the ages of 18 and 55 years, inclusive, in good health based on medical and psychiatric history, physical examination, ECG, orthostatic vital signs, and routine laboratory tests (blood chemistry, hematology, coagulation, and urinalysis).
- •Body mass index (BMI) between 18 and 30 kg/m2, inclusive.
- •Nonsmokers who have not used nicotine-containing products for at least 6 months prior to the Screening Visit.
排除标准
- •Actively participating in an experimental therapy study; received experimental therapy with a small molecule within 30 days of Day 1, or 5 half-lives, whichever is longer; or received experimental therapy with a large molecule within 90 days of Day 1, or 5 half-lives, whichever is longer.
- •A 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 as judged by the Investigator, including ventricular tachycardia, ventricular fibrillation, or atrial fibrillation.
- •Prolonged QTcF (>450 msec) based on the average of triplicate ECGs.
- •Seated blood pressure higher than 150/90 mmHg or lower than 90/50 mmHg.
- •Resting heart rate higher than 100 bpm or lower than 50 bpm , sinus node dysfunction, or clinically significant heart block.
- •Temperature (T) greater than 37.6o C (99.68o F, measured orally), and respiration rate less than 12 and greater than 20 breaths/minute.
- •Postural tachycardia (ie >30 bpm upon standing) or orthostatic hypotension (ie, a fall in systolic blood pressure (SBP) of ≥20 mm Hg or DBP of ≥ 10 mm Hg when a person assumes a standing position).
- •Serum potassium > upper limit of normal of the reference range (ULN) and serum sodium < lower limit of normal of the reference range (LLN).
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values > 1.2 ULN.
- •Positive for human immunodeficiency virus (HIV) antibody, hepatitis C virus (HCV) antibody, or Hepatitis B surface antigen (HBsAg).
- •A known history of porphyria, myopathy, or an active liver disease.
- •Positive drug or alcohol test result or a history of alcoholism or drug abuse within 2 years prior to the first dose of study drug as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition: DSM-IV.
- •Typical consumption of ≥14 alcoholic drinks weekly.
- •Surgical procedures within 4 weeks of check-in or planned elective surgery during the study period.
- •Currently undergoing treatment with weight loss medication or prior weight loss surgery (eg, gastric bypass surgery).
- •Pregnant, breastfeeding, or planning to become pregnant during the study.
研究组 & 干预措施
Cohort 1: 2.5 mg matching placebo
Subjects on a low salt diet
干预措施: Matching Placebo (Drug)
Cohort 3: 1.5 mg CIN-107
Subjects on a normal salt diet
干预措施: CIN-107 (Drug)
Cohort 2: 5.0 mg CIN-107
Subjects on a low salt diet
干预措施: CIN-107 (Drug)
Cohort 1: 2.5 mg CIN-107
Subjects on a low salt diet
干预措施: CIN-107 (Drug)
Cohort 5: 0.5 mg matching placebo
Subjects on a normal salt diet
干预措施: Matching Placebo (Drug)
Cohort 2: 5.0 mg matching placebo
Subjects on a low salt diet
干预措施: Matching Placebo (Drug)
Cohort 3: 1.5 mg matching placebo
Subjects on a normal salt diet
干预措施: Matching Placebo (Drug)
Cohort 4: 2.5 mg matching placebo
Subjects on a normal salt diet
干预措施: Matching Placebo (Drug)
Cohort 4: 2.5 mg CIN-107
Subjects on a normal salt diet
干预措施: CIN-107 (Drug)
Cohort 5: 0.5 mg CIN-107
Subjects on a normal salt diet
干预措施: CIN-107 (Drug)
结局指标
主要结局
Fraction of the dose excreted renally (fe)
时间窗: up to Day 15
This PK parameter will be calculated using the urine concentrations of CIN-107
Maximum plasma concentration (Cmax)
时间窗: up to Day 15
This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first and last doses of CIN-107, as the data permit.
Time to maximum plasma concentration (Tmax)
时间窗: up to Day 15
This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first and last doses of CIN-107, as the data permit.
Area under the curve from time 0 to the time of last quantifiable plasma concentration (AUC[0-last])
时间窗: up to Day 15
This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.
Area under the curve from time 0 to infinity
时间窗: up to Day 15
This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.
Area under the curve over a dosing interval (tau)
时间窗: up to Day 15
This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.
Area under the plasma concentration-time curve (AUC) from time 0 to 24 hours
时间窗: up to Day 2
This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first dose of CIN-107, as the data permit.
Apparent plasma clearance
时间窗: up to Day 15
This PK parameter will be determined for CIN-107 using plasma concentration data.
Apparent volume of distribution
时间窗: Up to Day 15
This PK parameter will be determined for CIN-107 using plasma concentration data.
The cumulative amount of CIN-107 and CIN-107-M excreted in the urine (Ae)
时间窗: up to Day 15
This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)
Renal clearance (CLR Calculated as Ae/AUC) of CIN-107 and CIN-107-M
时间窗: up to Day 15
This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)
Number of patients experiencing adverse events (AEs)
时间窗: up to Day 15
Number of patients experiencing adverse drug reactions
时间窗: up to Day 15
Number of patients experiencing serious adverse events (SAEs)
时间窗: up to Day 15
Plasma concentration of aldosterone
时间窗: up to Day 15
Plasma renin activity
时间窗: up to Day 15
Plasma concentration of cortisol (free and total)
时间窗: up to Day 15
Plasma concentration of ACTH (Adrenocorticotropic hormone)
时间窗: up to Day 15
Percent of AUC extrapolated
时间窗: up to Day 15
This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.
Terminal phase elimination half-life
时间窗: up to Day 15
This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.
次要结局
未报告次要终点