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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT01269294
First received: December 30, 2010
Last updated: May 3, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Drug: TMC435
Drug: Placebo for TMC435
Drug: Moxifloxacin
Drug: Placebo for moxifloxacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Double-dummy, Randomized, 4-period Cross-over, Placebo- and Positive-controlled Study to Evaluate the Effect of TMC435 on the QTc Interval in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Change in QT/QTc interval for TMC435 therapeutic dose versus placebo [ Time Frame: 24-hour measurement on Day 7 of Treatment Session A and D ] [ Designated as safety issue: No ]
  • Change in QT/QTc interval for TMC435 supratherapeutic dose versus placebo [ Time Frame: 24-hour measurement on Day 7 of Treatment Session B and D ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • RR interval, HR, PR interval, QRS interval and ECG morphology [ Time Frame: 1-hour predose measurement on Day 1 of every treatment session ] [ Designated as safety issue: No ]
  • RR interval, HR, PR interval, QRS interval and ECG morphology [ Time Frame: 24-hour measurement on Day 7 of every treatment session ] [ Designated as safety issue: No ]
  • Pharmacokinetics of 150 mg TMC435 once daily for 7 days [ Time Frame: Predose on Day 1 of every treatment and on Days 5 and 6 of Treatments A and B. 24 hour profile on Day 7 of Treatment A and B ] [ Designated as safety issue: No ]
  • Pharmacokinetics of 350 mg TMC435 once daily for 7 days [ Time Frame: Predose on Day 1 of every treatment and on Days 5 and 6 of Treatments A and B. 24 hour profile on Day 7 of Treatment A and B ] [ Designated as safety issue: No ]
  • Changes from baseline for electrocardiogram (ECG) and physical examination [ Time Frame: During all treatment sessions: Daily safety ECG from Day -1 to Day 9 with on Day 1 and 7 an additional safety ECG at 5h timepoint plus at screening and follow-up visits. Physical examination at screening, on Day 8 and at the follow-up visits ] [ Designated as safety issue: No ]
  • Number of participants with adverse events and severity of adverse events [ Time Frame: From signing of informed consent onwards until last trial-related visit ] [ Designated as safety issue: No ]
  • Changes from baseline and percentage of subjects with abnormal values for laboratory parameters [ Time Frame: At screening, on Days -1, 1, 5, 8 of all treatment sessions and at the follow-up visits ] [ Designated as safety issue: No ]
  • Changes from baseline and percentage of subjects with abnormal values for pulse and blood pressure [ Time Frame: At screening, daily from Day -1 to Day 9 with a second measurement on Day 7 of all treatment sessions and at the follow-up visits ] [ Designated as safety issue: No ]
  • Difference of QTc between moxifloxacin treatment and placebo treatment as a measure for trial sensitivity [ Time Frame: On Day 7 of Treatment C and D, at the 2, 3, 4 and 5 hour timepoints ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: January 2011
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
TMC435 2 capsules of 75 mg once daily for 7 days in Treatment A
Drug: TMC435
2 capsules of 75 mg once daily for 7 days in Treatment A
002
Placebo for TMC435 2 placebo capsules once daily for 7 days in Treatment A
Drug: Placebo for TMC435
2 placebo capsules once daily for 7 days in Treatment A
003
Placebo for moxifloxacin 1 placebo tablet on Day 7 of Treatments A B and D
Drug: Placebo for moxifloxacin
1 placebo tablet on Day 7 of Treatments A, B and D
Experimental: 004
TMC435 2 capsules of 75 mg and 2 capsules of 100 mg once daily for 7 days in Treatment B
Drug: TMC435
2 capsules of 75 mg and 2 capsules of 100 mg once daily for 7 days in Treatment B
005
Placebo for TMC435 4 placebo capsules once daily for 7 days in Treatment C
Drug: Placebo for TMC435
4 placebo capsules once daily for 7 days in Treatment C
006
Moxifloxacin 1 tablet of 400 mg on Day 7 of Treatment C
Drug: Moxifloxacin
1 tablet of 400 mg on Day 7 of Treatment C
Placebo Comparator: 007
Placebo for TMC435 4 placebo capsules once daily for 7 days in Treatment D
Drug: Placebo for TMC435
4 placebo capsules once daily for 7 days in Treatment D

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01269294

Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
  More Information

No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT01269294     History of Changes
Other Study ID Numbers: CR017491, TMC435-TiDP16-C117
Study First Received: December 30, 2010
Last Updated: May 3, 2013
Health Authority: Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Hepatitis C
TMC435-TiDP16-C117
TMC435-C117
TMC435
HCV
Moxifloxacin
ECG
QT
QTc

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Digestive System Diseases
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Combined
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014