Clinical trial NCT02217930: Study to Evaluate the Effect Of WCK 2349 on the QT/QTc Interval in Health Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Qt Interval, Variation in
Keywords: TQT
Lead sponsor: Wockhardt
Sponsor class: INDUSTRY
First posted: 2014-08-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Male or female subject between 18 and 55 years of age,inclusive, with a body mass index ≥18 to ≤33 kg/m2.
* 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.

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. 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).
5. Unstable cardiovascular disease, including recent myocardial infarction or cardiac arrhythmia.
6. Uncontrolled hypertension, asthma, unstable diabetes (type I or type II), thyroid disease, seizures, myasthenia gravis, or any other neuromuscular disorder.
7. Women who are pregnant (or planning to become pregnant within the next 6 months) or currently breastfeeding.

Primary outcomes:
measure: Change in QTc interval
timeFrame: Baseline and 48 hours
Secondary outcomes:
measure: Highest dose of WCK 2349 tolerated
timeFrame: Baseline and 48 hours
measure: Number of Adverse Events
timeFrame: Baseline and 7 days after the last dose
Other outcomes:
Locations:
city: West Bend
country: United States
facility: Phase 1 unit : Spaulding Clinical Research, LLC
state: Wisconsin
Study officials:
affiliation: Spaulding Clinical Research Inc.
name: Carlos Sanabria, MD
role: PRINCIPAL_INVESTIGATOR
References: