An Open Label Study to Investigate the Pharmacokinetics of CK-1827452 Administered Orally to Patients With Stable Heart Failure
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 3
- 主要终点
- C Max (Day 1, Dose 1)
研究概览
简要总结
This study is designed to understand the pharmacokinetics of different oral formulations of CK-1827452 being considered for future studies in patients with heart failure. This study will compare the pharmacokinetics and safety and tolerability of both modified-release (MR) and immediate-release (IR) oral formulations of CK-1827452.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient has signed an Informed Consent Form/Patient Information Sheet for this study approved by the governing Institutional Review Board (IRB) or Independent Ethics Committee (IEC)
- •The patient is at least 18 years old at the time of consent
- •Left ventricular ejection fraction (LVEF) ≤ 35% as determined by the Investigator within 3 weeks prior to enrollment
- •Treated for at least 4 weeks with a beta blocker and an ACE inhibitor (and/or an ARB) unless not tolerated. If prescribed, diuretics must have been administered according to a consistent regimen for at least 4 weeks.
- •Diagnosed with heart failure for ≥ 3 months prior to enrollment
- •Patient is considered to be an appropriate candidate for study enrollment as determined by the patient's clinical laboratory findings, vital signs and ECGs within normal range, or if outside of the normal range not deemed clinically significant in the opinion of the Investigator
- •For female patients only: The patient is post-menopausal (≥ 1 year) or sterilized, or if she is of childbearing potential, she is not breastfeeding, her pregnancy test is negative, she has no intention to become pregnant during the course of the study, and she is using contraceptive drugs or devices. For male patients only: Male patients agree for the duration of the study and 10 weeks after the end of the study to use a condom during sexual intercourse with female partners who are of reproductive potential and to have female partners use an additional effective means of contraception (eg, diaphragm plus spermicide, or oral contraceptives) or the male subject must agree to abstain from sexual intercourse for 10 weeks after the end of the study.
排除标准
- •Patient has been hospitalised for heart failure, acute coronary syndrome, myocardial infarction, coronary revascularisation, transient ischemic attack or stroke, cardiac arrhythmia, or major surgery within 6 weeks prior to enrollment
- •Poorly controlled hypertension defined as blood pressure > 150/95 mmHg, documented on at least 2 separate occasions prior to enrollment
- •The patient has a supine heart rate ≥ 100 beats per minute after 10 minutes of rest
- •Patient has a troponin I at screening that is above the upper limit of normal
- •The patient has severe aortic or mitral stenosis
- •The patient has active myocarditis; clinically significant restrictive, constrictive, or hypertrophic obstructive cardiomyopathy; clinically significant congenital heart disease; history of major organ transplantation
- •The patient has Canadian Cardiovascular Society Class IV angina
- •Patient is on chronic anti-arrhythmic therapy, with the exception of amiodarone
- •Patient has impaired renal function defined as an estimated GFR ≤ 30 ml/min/1.73 m2 calculated by the Modification of Diet in Renal Disease (MDRD) equation
- •Patient is currently taking, or has taken within 14 days prior to enrollment, a potent CYP3A4 inhibitor (medication or food). Patient is currently taking, or has taken within 28 days prior to enrollment, a potent CYP3A4 inducer (medication or food).
- •The patient has hepatic impairment defined as a total bilirubin > 3 mg/dL, or an ALT or AST > 2 times the upper limit of normal
- •Concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 1 year
- •The patient has received an investigational drug or device within 30 days or 5 half-lives, whichever is greater, of enrollment
- •Patient has, in the opinion of the Investigator, a condition that compromises the ability of the subject to give written informed consent or to comply with study procedures, including scheduled self-administration of oral CK-1827452
- •The patient has had any prior treatment with CK-1827452
研究组 & 干预措施
Cohort 1: MR 50 mg BID
Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.
干预措施: CK-1827452 (Drug)
Cohort 2: IR 37.5 mg TID
Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.
干预措施: CK-1827452 (Drug)
Cohort 3: MR 100 mg BID
Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
干预措施: CK-1827452 (Drug)
结局指标
主要结局
C Max (Day 1, Dose 1)
时间窗: 1 day
Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.
T Max (Day 1, Dose 1)
时间窗: 1 day
Time of observed maximum plasma concentration (T max) measured in hours (hr) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.
AUC (Day 1, Dose 1)
时间窗: 1 day
Area under the curve (AUC) measured in hours \* nanograms per milliliter (hr\*ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.
C Max (Day 10)
时间窗: 1 day
Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).
T Max (Day 10)
时间窗: 1 day
Time of observed maximum plasma concentration (T max) measured in hours (hr) post dose on day 10. Only one dose was administered on day 10 (final dose of study).
AUC (Day 10)
时间窗: 1 day
Area under the curve (AUC) measured in hours \* nanograms per milliliter (hr\*ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).
次要结局
- Evaluate the Safety and Tolerability of Oral Formulations of CK-1827452 When Dosed to Steady-state in Patients With Stable Heart Failure.(1 week)