A Randomized, Open-Label, Two-Period, Crossover Study to Evaluate the Effect of CIN-107 on the Pharmacokinetics of the MATE Substrate, Metformin, in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Percent of AUC extrapolated of metformin
研究概览
简要总结
This is a randomized, open-label, two-period, crossover Phase 1 to assess the impact of CIN-107 on the pharmacokinetics (PK) of metformin and the safety and tolerability of coadministration of CIN-107 and metformin as compared to metformin alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
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, at Screening;
- •Body mass index between 18 and 30 kg/m2, inclusive;
- •In good health based on medical/surgical and psychiatric history, physical examination, electrocardiogram (ECG), vital signs (seated and orthostatic), and routine laboratory tests (serum chemistry, hematology, and urinalysis);
- •Normal renal function, defined as estimated glomerular filtration rate ≥85 mL/min/1.73 m2 at Screening and Day -1;
- •Nonsmokers who have not used nicotine-containing products (ie, cigarettes, nicotine patch, nicotine chewing gum, or electronic cigarettes) for at least 6 months prior to Screening;
排除标准
- •Actively participating in an experimental therapy study; received experimental therapy with a small molecule other than CIN-107 within 30 days of the first dose of study drug or 5 half-lives, whichever is longer; or received experimental therapy with a large molecule within 90 days of the first dose of study drug or 5 half-lives, whichever is longer;
- •A personal or family history of long QT syndrome, Torsades de Pointes, 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, atrial fibrillation, sinus node dysfunction, or clinically significant heart block. Subjects with minor forms of ectopy (eg, premature atrial contractions) are not necessarily excluded and may be discussed with the Medical Monitor for inclusion;
- •Prolonged QT interval corrected by Fridericia's formula (>450 msec);
- •Seated systolic blood pressure (BP) >140 mmHg and/or diastolic BP >90 mmHg or systolic BP <90 mmHg and/or diastolic BP <50 mmHg;
- •Postural tachycardia (ie, >30 bpm upon standing) or orthostatic hypotension (ie, a fall in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg upon standing);
- •Serum potassium >upper limit of normal (ULN) of the reference range and serum sodium <lower limit of normal of the reference range;
- •Aspartate aminotransferase, alanine aminotransferase, or total bilirubin values >1.2 × ULN;
- •Positive for human immunodeficiency virus antibody, hepatitis C virus antibody, hepatitis B surface antigen, or severe acute respiratory syndrome coronavirus 2 RNA;
- •Evidence or history of any clinically significant immunologic, hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, musculoskeletal, hepatic, psychiatric, neurologic, or allergic (including clinically significant or multiple drug allergies) disease; surgical conditions; cancer (with the exception of basal or squamous cell carcinoma of the skin and cancer that has resolved or has been in remission for >5 years prior to Screening); or any condition that, in the Investigator's opinion, may confound study procedures or results, impact subject safety, or interfere with the absorption, distribution, metabolism, or excretion of the study drug (appendectomy allowed, cholecystectomy prohibited);
- •Typical consumption of ≥14 alcoholic drinks weekly; Note: 1 drink of alcohol is equivalent to ½ pint of beer (285 mL), 1 glass of spirits (25 mL), or 1 glass of wine (125 mL).
- •Surgical procedures within 4 weeks prior to Check-In (other than minor cosmetic surgery or minor dental procedures) or planned elective surgery during the treatment period;
研究组 & 干预措施
Treatment A: Immediate-release metformin
Treatment A: single 1000 mg dose of immediate-release metformin
Subjects will be randomly assigned to 1 of 2 sequences: AB or BA.
- Treatment A: a single 1000 mg dose of immediate-release metformin; and
- Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107.
All study medication will be administered at 8:00 AM (±2 hours). There will be a minimum 10-day washout between administration of study drug in each treatment period.
干预措施: Metformin (Drug)
Treatment B: Immediate-release metformin coadministered with a CIN-107
Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107
Subjects will be randomly assigned to 1 of 2 sequences: AB or BA.
- Treatment A: a single 1000 mg dose of immediate-release metformin; and
- Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107.
All study medication will be administered at 8:00 AM (±2 hours). For Treatment B, the dose of CIN-107 will be administered 2 hours prior to the dose of metformin.
There will be a minimum 10-day washout between administration of study drug in each treatment period.
干预措施: Metformin (Drug)
Treatment B: Immediate-release metformin coadministered with a CIN-107
Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107
Subjects will be randomly assigned to 1 of 2 sequences: AB or BA.
- Treatment A: a single 1000 mg dose of immediate-release metformin; and
- Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107.
All study medication will be administered at 8:00 AM (±2 hours). For Treatment B, the dose of CIN-107 will be administered 2 hours prior to the dose of metformin.
There will be a minimum 10-day washout between administration of study drug in each treatment period.
干预措施: CIN-107 (Drug)
结局指标
主要结局
Percent of AUC extrapolated of metformin
时间窗: Up to day 3
This plasma PK parameter will be determined for metformin.
Maximum plasma concentration (Cmax)
时间窗: Up to day 3
This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.
Terminal phase elimination half-life of metformin
时间窗: Up to day 3
This plasma PK parameter will be determined for metformin.
Time to Cmax (Tmax)
时间窗: Up to day 3
This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.
Area under the concentration-time curve (AUC) from time 0 to 72 hours
时间窗: Up to day 3
This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.
Maximum plasma concentration (Cmax) of metformin
时间窗: Up to day 3
This plasma PK parameter will be determined for metformin.
Time to Cmax (Tmax) of metformin
时间窗: Up to day 3
This plasma PK parameter will be determined for metformin.
AUC from time 0 to the time of last quantifiable plasma concentration of metformin
时间窗: Up to day 3
This plasma PK parameter will be determined for metformin.
AUC from time 0 to infinity of metformin
时间窗: Up to day 3
This plasma PK parameter will be determined for metformin.
Cumulative amount of metformin excreted in the urine (Ae) of metformin
时间窗: Up to day 3
This urine PK parameter will be determined for metformin.
Renal clearance (calculated as Ae/AUC) of metformin
时间窗: Up to day 3
This urine PK parameter will be determined for metformin.
Fraction of the dose excreted renally of metformin
时间窗: Up to day 3
This urine PK parameter will be determined for metformin.
次要结局
未报告次要终点