A First-in-Man, Phase I, Double-Blind, Randomized, Four-Way Crossover, Placebo-Controlled, Dose-Escalation, Pharmacokinetic and Pharmacodynamic Study of CK-1827452 (Omecamtiv Mecarbil) in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Omecamtiv Mecarbil in Healthy Volunteers
研究概览
简要总结
This study will assess the safety, tolerability, and pharmacodynamics of omecamtiv mecarbil infusion in healthy male volunteers.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Subject is male
- •Subject is aged between 18 and 50 years inclusive.
- •Subject has given signed informed consent.
- •Subject's Body Mass Index (BMI) is between 18 and 30 kg/m2 inclusive.
- •Subject weighs less than 100 kg.
- •Subject is considered to be in good health in the opinion of the investigator, as determined by:
- •A pre-study physical examination with no clinically significant abnormalities.
- •Vital signs within normal ranges (supine after 3 minutes rest - heart rate: 40 to 80 bpm; systolic BP: 100 to 140 mmHg; diastolic BP: 50-90 mmHg; respiration rate: 8 to 18 breaths per minute; oxygen saturation: 96-100%)
- •An ECG with no clinically significant abnormalities.
- •Subject's pre-study clinical laboratory findings are within normal range or if outside of the normal range not deemed clinically significant in the opinion of the investigator.
- •Cardiac troponin I is less than the upper limit of the laboratory reference range.
- •A screening echocardiogram demonstrates normal cardiac function, an ejection fraction of between 40% and 70% with no significant valvular regurgitation (grade 1) and/or stenosis and images are deemed to be of good quality by the sonographer.
排除标准
- •Subject has had a clinically significant illness in the four weeks before screening.
- •Use of prescribed mediations in the 3 weeks prior to dosing or over-the-counter preparations (including vitamin supplements and herbal remedies) for 7 days prior to dosing, except paracetamol which will be allowed up to 48 hours prior to dosing.
- •Subject has a significant history of drug/solvent abuse or a positive drugs of abuse test at screening.
- •Subject with a history of alcohol abuse or currently drinks in excess of 28 units per week.
- •Subject smokes more than 5 cigarettes (or equivalent) per day.
- •Subject is not willing to refrain from caffeine/xanthine containing products from 48 hours prior to the screening medical and admission on Day -1 until the post study medical.
- •Subject is in the opinion of the investigator not suitable to participate in the study.
- •Subject who has participated in any clinical study with an investigational drug/device within three months prior to the first day of dosing.
- •Subject who has a positive result of HIV screen, Hepatitis B screen or Hepatitis C screen.
- •Subject has had a serious adverse reaction or significant hypersensitivity to any drug.
- •Subject has donated 500 ml or more of blood within the month prior to screening.
- •Subject has a history of cardiovascular disease or family history of premature cardiovascular disease or death.
研究组 & 干预措施
Dose-escalation Cohort 1
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
干预措施: placebo (Drug)
Dose-escalation Cohort 1
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
干预措施: omecamtiv mecarbil (Drug)
Dose-escalation Cohort 2
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
干预措施: placebo (Drug)
Dose-escalation Cohort 2
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
干预措施: omecamtiv mecarbil (Drug)
Dose-escalation Cohort 3
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
干预措施: placebo (Drug)
Dose-escalation Cohort 3
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
干预措施: omecamtiv mecarbil (Drug)
Dose-escalation Cohort 4
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
干预措施: placebo (Drug)
Dose-escalation Cohort 4
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
干预措施: omecamtiv mecarbil (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Omecamtiv Mecarbil in Healthy Volunteers
时间窗: 2 days
The highest infusion rate tolerated by at least eight subjects. A dose was intolerable if: 1) the pattern of intolerance clearly distinguished active drug from placebo, or 2) the number of subjects intolerant of the dose level in question was at least 3 more than the number of subjects intolerant of placebo.
次要结局
- Change From Baseline of Systolic Ejection Time at Various Omecamtiv Mecarbil Infusion Rates(1 day)
- Change From Baseline of Fractional Shortening at Various Omecamtiv Mecarbil Infusion Rates(1 day)