A Randomized, Double-Blind, Double-Dummy, Placebo- and Positive- Controlled, Crossover Study to Evaluate the Effect Of WCK 2349 on the QT/QTc Interval in Health Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Wockhardt
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change in QTc interval
研究概览
简要总结
The study designed to determine the effect induced by WCK 2349 on the QT interval.
The study will be conducted in two parts: 1) to determine the supratherapeutic dose; and 2) to assess the safety of high doses of single-dose administration of WCK 2349 on the QT interval.
详细描述
Part 1 of this study will determine the supratherapeutic dose to be used in Part 2. Part 1will enroll 8 subjects at each of 4 dose levels (up to 32 subjects). Cohorts will be staggered so that appropriate safety monitoring and follow-up can be performed for each subject at each dose level.
Safety monitoring will be based upon review of AEs, ECGs and clinical laboratory test results prior to escalation to the next dose level.
At the first dose level, 6 subjects will be randomly assigned to receive a single dose of WCK 2349 at 1800 mg and 2 subjects will be randomly assigned to placebo. If this dose is tolerated by subjects, and safety data allows, the next group will be initiated in the same fashion at a dose of 2200 mg. If this dose is tolerated by subjects, and safety data allows, the next group will be initiated in the same fashion at a dose of 2600 mg. If this dose is tolerated by subjects, and safety data allows, the next group will be initiated in the same fashion at a dose of 3000 mg. Based upon safety data, the highest safely tolerated dose in Part 1 will be utilized as the supratherapeutic dose in Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Male or female subject between 18 and 55 years of age,inclusive, with a body mass index ≥18 to ≤33 kg/m
- •Female subjects must be at least 2 years postmenopausal,surgically sterile, or practicing 2 highly effective methods of birth control (determined by the investigator or designee; one of the methods must be a barrier technique), not pregnant or lactating, and have a negative serum pregnancy test before enrolling in the study.
- •Male or female subjects must agree to practice 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from Screening until 30 days after the last dose of study drug.
- •Stable health based on no clinically significant findings on the medical history, physical examination, or clinical laboratory test results (as determined and documented by the investigator).
- •Willing to comply with all study activities and procedures and provides written informed consent prior to any study procedures.
排除标准
- •An uninterpretable or abnormal screening electrocardiogram (ECG) indicating a second- or third-degree atrioventricular block, or one or more of the following: QRS interval >110 milliseconds (msec); QT interval corrected by Fridericia's formula (QTcF) >430 msec (males) and >450 msec (females); PR interval >200 msec; heart rate (HR) <45 bpm; or any rhythm other than sinus rhythm that is interpreted by the investigator to be clinically significant.
- •History of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesemia. Subjects will also be excluded if there is a family history of long QT syndrome or Brugada syndrome.
- •A sustained supine systolic blood pressure >150 mm Hg or <90 mm Hg or a supine diastolic blood pressure >95 mm Hg or <50 mm Hg at Screening or Check-in (Day -1). Blood pressure may be retested once in the supine position. The blood pressure abnormality is considered sustained if either the systolic or the diastolic pressure values are outside the stated limits after 2 assessments, and the subject may not be randomized.
- •A resting HR of <40 beats per minute or >100 beats per minute when vital signs are measured at Screening or Check-in (Day -1).
- •Unstable cardiovascular disease, including recent myocardial infarction or cardiac arrhythmia.
- •Uncontrolled hypertension, asthma, unstable diabetes (type I or type II), thyroid disease, seizures, myasthenia gravis, or any other neuromuscular disorder.
- •Women who are pregnant (or planning to become pregnant within the next 6 months) or currently breastfeeding.
研究组 & 干预措施
Placebo
Placebo matched to WCK 2349, oral tablet(s)
Placebo matched to moxifloxacin overencapsulated tablet
干预措施: Placebo (Drug)
Moxifloxacin
Moxifloxacin 400 mg positive control (overencapsulated tablet)
干预措施: Moxifloxacin (Drug)
WCK 2349
WCK 2349 supratherapeutic dose determined in Part 1, oral tablet(s)
干预措施: WCK 2349 (Drug)
结局指标
主要结局
Change in QTc interval
时间窗: Baseline and 48 hours
次要结局
- Number of Adverse Events(Baseline and 7 days after the last dose)
- Highest dose of WCK 2349 tolerated(Baseline and 48 hours)