A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Multi-Part, Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects.
研究概览
简要总结
The purposes of this study are to:
- Learn about the safety of CK-3773274 after a single dose and multiple doses in healthy subjects.
- Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses.
- Find out how much CK-3773274 is in the blood after a single dose and multiple doses.
- Determine the effect of doses of CK-3773274 on the pumping function of the heart.
- Evaluate the effect of cytochrome genetic variants on how the body metabolizes CK-3773274.
- Evaluate the effect of a meal on how much CK-3773274 is in the blood in healthy adult subjects.
- Evaluate whether the amount of CK-3773274 in the blood is the similar for both the tablet and granules in capsule forms of the drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, 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
- •Males and females (of non-childbearing potential) between 18 and 55 years of age, inclusive
- •Body weight > 55.0 kg and body mass index within 18.0 to 32.0 kg/m2, inclusive
- •Normal cardiac structure and function, or if abnormalities are present, they are deemed not clinically significant
- •Normal to high left ventricular ejection fraction.
- •Normal electrocardiogram (ECG) or, if abnormalities are present, they are deemed not clinically significant
- •Clinical laboratory findings within normal range
- •Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C antibody), and negative human immunodeficiency virus antibody screens
- •Willing and able to refrain from strenuous exercise (eg, activity which could be expected to cause muscle soreness)
- •For Arms 5 and 6 only: Subject is a CYP2D6 poor metabolizer
排除标准
- •History of any significant illness or disorder
- •History of stomach or intestinal surgery or resection (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
- •A clinically significant illness within 4 weeks of Check-in
- •Inability to swallow capsules or tablets
- •History of or current substance abuse (drug or alcohol), known drug or alcohol dependence within the last 2 years prior to Screening, or positive test for drugs of abuse during the screening period
- •Use of any tobacco-containing or nicotine-containing products within 3 months prior to Check-in
- •Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days prior to Check-in
- •Any blood donation within 60 days of dosing, plasma donation within 30 days of dosing, or receipt of blood products within 2 months prior to Check-in
研究组 & 干预措施
Placebo for SAD Cohorts
Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo
干预措施: Placebo - Granules in Capsule (Drug)
CK-3773274 for MAD Cohorts
Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274
干预措施: CK-3773274 - Granules in Capsule (Drug)
Placebo for MAD Cohorts
Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo
干预措施: Placebo - Granules in Capsule (Drug)
CK-3773274 for SAD Cohorts
Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274
干预措施: CK-3773274 - Granules in Capsule (Drug)
CK-3773274 for CYP2D6 Cohort
Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274
干预措施: CK-3773274 - Granules in Capsule (Drug)
Placebo for CYP2D6 Cohort
Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo
干预措施: Placebo - Granules in Capsule (Drug)
Food Effect
Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion
干预措施: CK-3773274 - Granules in Capsule (Drug)
Relative Bioavailability
Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion.
干预措施: CK-3773274 - Granules in Capsule (Drug)
Relative Bioavailability
Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion.
干预措施: CK-3773274 - Tablets (Drug)
结局指标
主要结局
Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects.
时间窗: SAD Cohorts: Day -1 - Day 10; CYP2D6 Cohort: Day -1 - Day - 24; MAD Cohorts: Day -1 - Day 27; Food Effect Cohort: Day -1 - Day 24; relative Bioavailability Cohort: Day -1 - Day 29
Subject incidence of AEs, SAEs, and reduced LVEF
次要结局
- Cmax of CK-3773274 after single and multiple ascending doses(SAD Cohorts: Day 1; CYP2D6 Cohort: Day 1; MAD Cohorts: Day 14 or Day 17; Food Effect Cohort: Day 15; Relative Bioavailability Cohort: Day 15)
- Change in absolute reduction in ejection fraction relative to baseline with doses of CK-3773274(Time Frame for SAD Cohorts: Day -1 - Day 10; Time Frame for CYP2D6 Cohort: Day -1 - Day 24; Time Frame for MAD Cohorts: Day -1 - Day 27)
- Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274(Day -1 - Day 24)
- Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects(Day -1 - Day 24)
- Relative bioavailability of CK-3773274 formulated as granules in capsule versus a tablet in healthy adult subjects(Time Frame for Bioavailability Cohort: Day -1 - Day 29)