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TMC207TBC1003 - A Study in Healthy Volunteers Investigating the Effect of Single-dose TMC207 on the QT/QTc Interval Under Fed Conditions

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ClinicalTrials.gov Identifier: NCT01291563
Recruitment Status : Completed
First Posted : February 8, 2011
Last Update Posted : November 6, 2012
Sponsor:
Information provided by (Responsible Party):
Tibotec BVBA

Brief Summary:
The purpose of this study is to evaluate the effect of an 800-mg single dose of TMC207 on the QT/QTc interval in healthy volunteers.

Condition or disease Intervention/treatment Phase
Healthy Volunteer Drug: Moxifloxacin Drug: TMC207 Drug: TMC207 placebo Drug: Moxifloxacin placebo Phase 1

Detailed Description:
TMC207 is being investigated for the treatment of M. Tuberculosis (MTB, formerly known as TBC) infection. This study is designed to establish the effect of a single dose of TMC207 on the QT/QTc interval in healthy volunteers under fed conditions. This is a Phase I, double-blind (study doctor nor participants will know which treatment will be received), randomized (study medication is assigned by chance, like tossing a coin), placebo- and active-controlled study to evaluate the effect of single-dose TMC207 on the QT/QTc interval in healthy volunteers. A single dose of 400 mg moxifloxacin will be used as a positive control to assess trial sensitivity. The trial population will consist of 88 healthy volunteers. Forty-four participants will be randomized to Group 1, and 22 participants will be randomized to each of the Groups 2 and 3. Each gender should be represented by at least 40%. Each participant will receive one of the Treatments A or B in one treatment session. Participants in Group 1 will take a single 800-mg dose of TMC207 on Day 1 and a single dose of moxifloxacin placebo on Day 2 (Treatment A). Participants in Groups 2 and 3 will take a single dose of TMC207 placebo on Day 1 and a single 400-mg dose of moxifloxacin on Day 2 (Treatment B). All intakes of TMC207, moxifloxacin, TMC207 placebo and moxifloxacin placebo will be taken with standardized meals. The duration of the study will be 3 days, screening and follow-up period not included. On Days -1, 1, and 2 of Treatment A and B, electrocardiograms (ECGs) will be recorded continuously for 24 hours per day by Holter monitoring. Safety assessments (blood and urine tests, blood pressure, pulse, electrocardiogram, and physical examination) will follow a similar schedule and will be performed during each treatment period, up to 4 weeks after the last study drug intake.The pharmacokinetic characteristics (level-profile of TMC207 and moxifloxacin over time in the blood stream) will be evaluated by multiple blood samples from Day -1 tol Day 3. Participants in Group 1 will take a single 800-mg dose of TMC207 on Day 1 and a single dose of moxifloxacin placebo on Day 2 (Treatment A). Participants in Groups 2 and 3 will take a single dose of TMC207 placebo on Day 1 and a single 400-mg dose of moxifloxacin on Day 2 (Treatment B).¿ The study duration will be 3 days without screening and follow-up period included.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo- and Active-controlled, Parallel-group Trial to Evaluate the Effect of Single-dose TMC207 on the QT/QTc Interval in Healthy Subjects
Study Start Date : February 2011
Actual Study Completion Date : April 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 001
TMC207 8 tablets of TMC207 (100 mg/tablet) on Day 1
Drug: TMC207
8 tablets of TMC207 (100 mg/tablet) on Day 1

Placebo Comparator: 002
TMC207 placebo 8 tablets of TMC207 placebo on Day 1
Drug: TMC207 placebo
8 tablets of TMC207 placebo on Day 1

Active Comparator: 003
Moxifloxacin 1 capsule of moxifloxacin (400 mg/capsule) on Day 2
Drug: Moxifloxacin
1 capsule of moxifloxacin (400 mg/capsule) on Day 2

Placebo Comparator: 004
Moxifloxacin placebo 1 capsule of moxifloxacin placebo on Day 2
Drug: Moxifloxacin placebo
1 capsule of moxifloxacin placebo on Day 2




Primary Outcome Measures :
  1. ECG evaluation as a measure of QT and QTc interval [ Time Frame: Measured Day -1 to Day 3 ]

Secondary Outcome Measures :
  1. ECG evaluation as a measure of non-QT interval electrocardiogram parameters (RR interval, HR, PR and QRS interval) [ Time Frame: Measured on Day -1 until Day 3 ]
  2. Plasma concentrations of TMC207 and its N-monodesmethyl metabolite (M2) [ Time Frame: Measured on Day -1 until Day 3 ]
  3. Evaluation of the concentration-effect relationship for QT/QTc for TMC207 and M2 [ Time Frame: Measured on Day -1 until Day 3 ]
  4. Evaluation of the number of volunteers with adverse events, blood and urine tests, blood pressure and pulse tests, and ECGs as measures of safety and tolerability [ Time Frame: Measured on Day -1 until Day 3 and Day 8-10 and 30 to 32 days after last study drug intake as safety follow up ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy on the basis of physical examination, medical history, vital signs, electrocardiogram, and clinical laboratory tests at screening
  • A Body Mass Index of 18.0 to 28.0 kg/m2, extremes included
  • Women must be postmenopausal for at least two years, be surgically sterile and must have negative serum pregnancy test at screening
  • Non-smoking for at least three months prior to selection.

Exclusion Criteria:

  • Infection with Hepatitis A, B, or C virus
  • Infection with the human immunodeficiency virus (HIV)
  • History of, or any current medical condition which could impact the safety of the participant in the study
  • Previously participated in a TMC207 trial or received an investigational drug or vaccine within 60 days before the planned start of treatment
  • A positive urine drug test at screening
  • Volunteers with a clinically significant ECG abnormality or any other cardiac history (unusual T wave morphology, history of additional risk for Torsade de Pointes, electrolyte abnormalities, blood pressure outside of the normal range, or history of a clinically relevant heart rhythm disturbance or with a family history of Long QT Syndrome)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01291563


Sponsors and Collaborators
Tibotec BVBA
Investigators
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Study Director: Tibotec-Virco Virology BVBA Clinical Trial Tibotec BVBA

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Responsible Party: Tibotec BVBA
ClinicalTrials.gov Identifier: NCT01291563     History of Changes
Other Study ID Numbers: CR017167
TMC-207-TBC1003
First Posted: February 8, 2011    Key Record Dates
Last Update Posted: November 6, 2012
Last Verified: November 2012

Keywords provided by Tibotec BVBA:
TMC207TBC1003
TMC207
M.Tuberculosis
TBC
Moxifloxacin
ECG
QT/QTc
Healthy volunteers

Additional relevant MeSH terms:
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Bedaquiline
Moxifloxacin
Diarylquinolines
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antitubercular Agents