A Phase 1, Randomized, Placebo and Active Controlled, Double-Blind, Parallel, Electrocardiogram Study to Evaluate the Effect of Lumacaftor in Combination With Ivacaftor on the QT/QTc Interval in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 200
- 主要终点
- (Part A) Safety and tolerability of lumacaftor as measured by standard 12-lead ECGs, adverse events (AEs), vital signs, spirometry, and clinically significant laboratory assessments
研究概览
简要总结
This study is designed to evaluate the effect of multiple doses of lumacaftor in combination with ivacaftor on cardiac repolarization, as detected by QT/QTc interval corrected for heart rate in healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Subjects must be willing and able to comply with scheduled visits, treatment plan, lifestyle guidelines, laboratory tests, contraceptive guidelines, and other study procedures.
- •Subjects must be healthy, as defined by no clinically relevant abnormalities identified by a detailed medical history, physical examination, including blood pressure and pulse rate measurement, and 12 lead ECG.
- •Subjects must weigh >50kg
排除标准
- •Abnormal renal function at Screening
- •Plasma donation within 7 days before first study drug dose or blood donation of 1 pint (500mL) within 56 days before first study drug dose
- •Positively screen for Hepatitis B, Hepatitis C, HIV
- •Known hypersensitivity or prior adverse reaction to moxifloxacin or other quinolones
- •Any condition possibly affecting drug absorption (e.g., gastrectomy, or other gastrointestinal tract surgery, except appendectomy or cholecystectomy or polypectomy) or regular use of acid-lowering therapies (H2 blockers, proton pump inhibitors, and antacids).
- •Female subjects who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last study drug dose and female subjects of childbearing potential who are unwilling or unable to follow the contraceptive guidelines from at least 14 days before the first study drug dose.
- •Male subject who has a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last study drug dose; male subjects who are unwilling or unable to follow the contraceptive guidelines
研究组 & 干预措施
Part A
Will consist of up to 4 cohorts with subjects receiving lumacaftor or placebo for 7 days.
Cohort 1: 600 mg lumacaftor once a day Cohort 2: 1000 mg lumacaftor once a day Cohort 3: 1200 mg lumacaftor once a day
干预措施: Lumacaftor (Drug)
Part A
Will consist of up to 4 cohorts with subjects receiving lumacaftor or placebo for 7 days.
Cohort 1: 600 mg lumacaftor once a day Cohort 2: 1000 mg lumacaftor once a day Cohort 3: 1200 mg lumacaftor once a day
干预措施: Lumacaftor Placebo (Drug)
Part B
Will consist of 3 cohorts. All cohorts will be dosed in parallel. Cohort A will receive 600 mg Lumacaftor once a day plus 250 mg Ivacaftor twice a day for 7 days. From day 8-14 subjects will receive a supratherapeutic dose of Lumacaftor (TBD) plus 450 mg Ivacaftor twice a day.
Cohort B will receive lumacaftor and ivacaftor matching placebo for 14 days Cohort C will receive a single dose of 400 mg moxifloxacin on day 14
干预措施: Lumacaftor (Drug)
Part B
Will consist of 3 cohorts. All cohorts will be dosed in parallel. Cohort A will receive 600 mg Lumacaftor once a day plus 250 mg Ivacaftor twice a day for 7 days. From day 8-14 subjects will receive a supratherapeutic dose of Lumacaftor (TBD) plus 450 mg Ivacaftor twice a day.
Cohort B will receive lumacaftor and ivacaftor matching placebo for 14 days Cohort C will receive a single dose of 400 mg moxifloxacin on day 14
干预措施: Lumacaftor Placebo (Drug)
Part B
Will consist of 3 cohorts. All cohorts will be dosed in parallel. Cohort A will receive 600 mg Lumacaftor once a day plus 250 mg Ivacaftor twice a day for 7 days. From day 8-14 subjects will receive a supratherapeutic dose of Lumacaftor (TBD) plus 450 mg Ivacaftor twice a day.
Cohort B will receive lumacaftor and ivacaftor matching placebo for 14 days Cohort C will receive a single dose of 400 mg moxifloxacin on day 14
干预措施: Ivacaftor (Drug)
Part B
Will consist of 3 cohorts. All cohorts will be dosed in parallel. Cohort A will receive 600 mg Lumacaftor once a day plus 250 mg Ivacaftor twice a day for 7 days. From day 8-14 subjects will receive a supratherapeutic dose of Lumacaftor (TBD) plus 450 mg Ivacaftor twice a day.
Cohort B will receive lumacaftor and ivacaftor matching placebo for 14 days Cohort C will receive a single dose of 400 mg moxifloxacin on day 14
干预措施: Ivacaftor Placebo (Drug)
Part B
Will consist of 3 cohorts. All cohorts will be dosed in parallel. Cohort A will receive 600 mg Lumacaftor once a day plus 250 mg Ivacaftor twice a day for 7 days. From day 8-14 subjects will receive a supratherapeutic dose of Lumacaftor (TBD) plus 450 mg Ivacaftor twice a day.
Cohort B will receive lumacaftor and ivacaftor matching placebo for 14 days Cohort C will receive a single dose of 400 mg moxifloxacin on day 14
干预措施: moxifloxacin hydrochloride (Drug)
结局指标
主要结局
(Part A) Safety and tolerability of lumacaftor as measured by standard 12-lead ECGs, adverse events (AEs), vital signs, spirometry, and clinically significant laboratory assessments
时间窗: 7 days
(Part B) Time matched, baseline-adjusted change in QTcF intervals obtained from a continuous ECG recording over a 24 hour interval after administration of a therapeutic and supratherapeutic dose of lumacaftor in combination with ivacaftor
时间窗: 7 days
次要结局
- (Part A) PK parameters of lumacaftor and M28-lumacaftor in plasma including Cmax and AUC(up to 11 days)
- (Part B) Time-matched, baseline-adjusted QTcF intervals obtained after a single 400-mg dose of moxifloxacin(up to 14 days)
- (Part B) Time-matched, baseline-adjusted non-QT interval parameters obtained from a continuous ECG recording over a 24-hour interval(up to 14 days)
- (Part B) PK parameters of lumacaftor, M28-lumacaftor, ivacaftor, M1-ivacaftor, and M6-ivacaftor including Cmax and AUC(up to 15 days)
- (Part B) PK/PD relationship between plasma concentration and QT/QTc interval(up to 14 days)
- (Part B) Safety and tolerability of lumacaftor in combination with ivacaftor as measured by standard 12-lead ECGs, AEs, vital signs, and clinical significant laboratory results(up to 24 days)