Study to Evaluate the Effect Of WCK 2349 on the QT/QTc Interval in Health Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Qt Interval, Variation in
• Intervention / Treatment: Drug: Placebo; Drug: Moxifloxacin; Drug: WCK 2349

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Phase 1 unit : Spaulding Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo matched to WCK 2349, oral tablet(s) Placebo matched to moxifloxacin overencapsulated tablet	Drug: Placebo
Active Comparator: Moxifloxacin; Moxifloxacin 400 mg positive control (overencapsulated tablet)	Drug: Moxifloxacin
Experimental: WCK 2349; WCK 2349 supratherapeutic dose determined in Part 1, oral tablet(s)	Drug: WCK 2349

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in QTc interval	Baseline and 48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Highest dose of WCK 2349 tolerated	Baseline and 48 hours
Number of Adverse Events	Baseline and 7 days after the last dose

Collaborators and Investigators

• Sponsor: Wockhardt
• Investigators: Principal Investigator: Carlos Sanabria, MD, Spaulding Clinical Research Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: July 31, 2014
• First Submitted That Met QC Criteria: August 13, 2014
• First Posted (Estimate): August 15, 2014

Study Record Updates

• Last Update Posted (Estimate): October 29, 2015
• Last Update Submitted That Met QC Criteria: October 28, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: TQT
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: W-2349-101