Single-center, Open-label, Randomized, Multiple-dose, Parallel-group Study to Investigate Safety and Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of ACT-334441 Combined With Calcium-channel Blocker (Diltiazem) or Beta-blocker (Atenolol) Treatment in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Hourly mean heart rate (HR) measured by 24-hour Holter ECG
研究概览
简要总结
The aim of the study is to investigate the safety of the concomitant administration of ACT-334441 with cardiovascular drugs.
详细描述
The study will consist of two parts: a pilot part (Part A) that will be completed prior to the start of the main part (Part B). The Subjects who will participate in Part A are excluded from Part B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent
- •Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
- •Women of childbearing potential must have a negative pregnancy test and they must use reliable methods of contraception
- •Healthy on the basis of physical examination,cardiovascular assessments and laboratory tests
排除标准
- •Pregnant or lactating women
- •Any contraindication to the study drugs
- •History or presence of any disease or condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study drugs
- •Any clinically significant abnormalities in laboratory tests, vital signs, ECG variables and pulmonary variables
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol
研究组 & 干预措施
Part A ACT-334441 + atenolol
4 subjects will receive 50 mg of atenolol once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6
干预措施: ACT-334441 2 mg (Drug)
Part A ACT-334441 + atenolol
4 subjects will receive 50 mg of atenolol once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6
干预措施: Atenolol (Drug)
Part A ACT-334441 + diltiazem
4 subjects will receive 240 mg of diltiazem once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6
干预措施: ACT-334441 2 mg (Drug)
Part A ACT-334441 + diltiazem
4 subjects will receive 240 mg of diltiazem once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6
干预措施: Diltiazem ER (Drug)
Part B ACT-334441 + atenolol
12 subjects will receive 50 mg of atenolol (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15
干预措施: ACT-334441 4 mg (Drug)
Part B ACT-334441 + atenolol
12 subjects will receive 50 mg of atenolol (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15
干预措施: Placebo (Drug)
Part B ACT-334441 + atenolol
12 subjects will receive 50 mg of atenolol (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15
干预措施: Atenolol (Drug)
Part B ACT-334441 + diltiazem
12 subjects will receive 240 mg of diltiazem (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15
干预措施: ACT-334441 4 mg (Drug)
Part B ACT-334441 + diltiazem
12 subjects will receive 240 mg of diltiazem (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15
干预措施: Placebo (Drug)
Part B ACT-334441 + diltiazem
12 subjects will receive 240 mg of diltiazem (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15
干预措施: Diltiazem ER (Drug)
结局指标
主要结局
Hourly mean heart rate (HR) measured by 24-hour Holter ECG
时间窗: Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B
Absolute and change from baseline in hourly mean HR on each day of measurement
PR intervals measured by 12-lead ECG (Part A + Part B)
时间窗: Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B)
Absolute PR intervals and corresponding changes from baseline at the different days of measurement
Heart rate (HR) measured by 12-lead ECG (PArt A + Part B)
时间窗: Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B)
Absolute heart rates at the different days of measurement
次要结局
- Number of subjects with adverse events as a measure of safety(From baseline to end of study [Day 20-23 (Part A), Day 556-59 (Part B)])
- Areas under the plasma concentration-time curves (AUC) for ACT-334441, diltiazem and atenolol (Part B)(Blood samples from Day 1 to Day 20 for the PK profile of diltiazem and atenolol, and from Day 8 to Day 21 for the PK profile of ACT-334441.)
- Trough plasma levels (Ctrough) of of ACT-334441, diltiazem and atenolol (Part B)(From Day 1 to Day 15 for diltiazem and atenolol; from Day 8 to Day 15 for ACT-33444)
- Time to reach the maximum plasma concentration (tmax) for ACT-334441, diltiazem and atenolol (Part B)(From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444)
- Terminal half-life [t(1/2)] of ACT-334441, diltiazem and atenolol (Part B)(From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444)
- Maximum plasma concentration (Cmax) for ACT-334441, diltiazem and atenolol (Part B)(From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444.)