TMC435-TiDP16-C117: The Effect of TMC435 on the Results of Electrocardiograms (Electric Recording of the Heart) in Healthy Volunteers

Tibotec Pharmaceutical

Status and phase: Completed; Phase 1

Conditions: Hepatitis C

Treatments: Drug: TMC435; Drug: Moxifloxacin; Drug: Placebo for TMC435; Drug: Placebo for moxifloxacin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01269294

TMC435-TiDP16-C117 (Other Identifier)

CR017491

Details and patient eligibility

About

The purpose of this study is to evaluate the effect of TMC435 on the results of electrocardiograms (ECGs) in healthy volunteers. An electrocardiogram is an electric recording of the heart. TMC435 is being investigated for the treatment of chronic hepatitis C virus infection.

Full description

This is a double-blind, double-dummy, randomized, 4-period cross-over, placebo- and positive-controlled, Phase I study. This means neither the study doctor nor the participants know in which treatment session you will receive which active medication or matching placebo. Every participant will receive 4 treatment sessions (Treatments A, B, C and D) in a different order. The order in which you receive the treatment sessions is determined by chance, like tossing a coin. The purpose of the study is to evaluate the effect of TMC435 on the results of electrocardiograms (electric recording of the heart). Two dose regimens of TMC435 will be tested, ie, 150 mg once daily (the dose that will be given to patients) and 350 mg once daily (a dose higher than the one that will be given to patients), administered for 7 days. A single dose of 400 mg moxifloxacin will be used as a positive control to assess trial sensitivity. The trial population will consist of 60 healthy volunteers of which approximately 18 will be females. In each treatment, dummy capsules will be added in order to have the same number of capsules in each treatment. Treatment A will consist of 150 mg TMC435 once daily for 7 days (2 capsules of TMC435 and 2 capsules placebo on days 1-7, 1 placebo tablet for moxifloxacin on Day 7). Treatment B will consist of 350 mg TMC435 once daily for 7 days (4 capsules of TMC435 on Days 1-7, 1 placebo tablet for moxifloxacin on Day 7). Treatment C will consist of 400 mg moxifloxacin on Day 7 (4 capsules of placebo for TMC435 on Days 1-7, 1 moxifloxacin tablet on Day 7). In Treatment D only placebo will be given (4 capsules of placebo for TMC435 on Days 1-7, 1 placebo tablet for moxifloxacin on Day 7). There will be a washout period of at least 10 days between subsequent treatments. A pharmacogenomic blood sample (DNA sample, blood sample from which your genetic information can be analyzed) will be collected from all volunteers and will be analyzed upon observation of irregular electrocardiogram during the study. The purpose is to see if irregularities in the electrocardiogram can be linked to genetic variants. DNA samples may also be analyzed for additional genes related to pharmacokinetics (what the body does with the drug), pharmacodynamics (what the drug does to your body) or safety and tolerability of TMC435 during the study, as necessary. Two oral doses of TMC435 (150 or 350 mg) or placebo will be given once daily for 7 consecutive days. A single dose of moxifloxacin 400 mg will be administered orally on Day 7 in one of the treatment sessions only.

Enrollment: 60 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Non-smokers for at least six months
• Have a body mass index of 18.0 to 30.0 kg per square meter
• Be healthy on the basis of physical examination, medical history, vital signs, and clinical laboratory tests performed at screening.

Exclusion criteria

• Use of disallowed therapies, including over-the-counter products and dietary supplements
• Any skin condition likely to interfere with ECG electrode placement or adhesion
• History or evidence of current use of alcohol or recreational or narcotic drug use
• Clinically relevant abnormality on ECG at screening or history of clinically relevant heart rhythm disturbances.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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60 participants in 7 patient groups, including a placebo group

001

Experimental group

Description:

TMC435 2 capsules of 75 mg once daily for 7 days in Treatment A

Treatment:

Drug: TMC435

Drug: TMC435

002

Other group

Description:

Placebo for TMC435 2 placebo capsules once daily for 7 days in Treatment A

Treatment:

Drug: Placebo for TMC435

Drug: Placebo for TMC435

Drug: Placebo for TMC435

003

Other group

Description:

Placebo for moxifloxacin 1 placebo tablet on Day 7 of Treatments A B and D

Treatment:

Drug: Placebo for moxifloxacin

004

Experimental group

Description:

TMC435 2 capsules of 75 mg and 2 capsules of 100 mg once daily for 7 days in Treatment B

Treatment:

Drug: TMC435

Drug: TMC435

005

Other group

Description:

Placebo for TMC435 4 placebo capsules once daily for 7 days in Treatment C

Treatment:

Drug: Placebo for TMC435

Drug: Placebo for TMC435

Drug: Placebo for TMC435

006

Other group

Description:

Moxifloxacin 1 tablet of 400 mg on Day 7 of Treatment C

Treatment:

Drug: Moxifloxacin

007

Placebo Comparator group

Description:

Placebo for TMC435 4 placebo capsules once daily for 7 days in Treatment D

Treatment:

Drug: Placebo for TMC435

Drug: Placebo for TMC435

Drug: Placebo for TMC435