Hepatitis CPhase 1NCT01269294
TMC435-TiDP16-C117: The Effect of TMC435 on the Results of Electrocardiograms (Electric Recording of the Heart) in Healthy Volunteers
A Phase 1 study testing TMC435 and Moxifloxacin in people with Hepatitis C, run by Tibotec Pharmaceuticals, Ireland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C
- What is being tested?
- TMC435 and Moxifloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Jan 2011to Jul 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
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
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.
Read the 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.
- Conditions
- Hepatitis C
- Being tested
- TMC435, Placebo for TMC435, Moxifloxacin, Placebo for moxifloxacin
- Keywords
- Hepatitis C, TMC435-TiDP16-C117, TMC435-C117, TMC435, HCV, Moxifloxacin, ECG, QT, QTc
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC435Drug
2 capsules of 75 mg once daily for 7 days in Treatment A
Placebo for TMC435Drug
4 placebo capsules once daily for 7 days in Treatment C
TMC435Drug
2 capsules of 75 mg and 2 capsules of 100 mg once daily for 7 days in Treatment B
Placebo for TMC435Drug
2 placebo capsules once daily for 7 days in Treatment A
MoxifloxacinDrug
1 tablet of 400 mg on Day 7 of Treatment C
Placebo for moxifloxacinDrug
1 placebo tablet on Day 7 of Treatments A, B and D
Placebo for TMC435Drug
4 placebo capsules once daily for 7 days in Treatment D
| Study group | Role | What they receive |
|---|---|---|
| 001 | Experimental | TMC435 2 capsules of 75 mg once daily for 7 days in Treatment A Receives: Drug: TMC435 |
| 002 | Other | Placebo for TMC435 2 placebo capsules once daily for 7 days in Treatment A Receives: Drug: Placebo for TMC435 |
| 003 | Other | Placebo for moxifloxacin 1 placebo tablet on Day 7 of Treatments A B and D Receives: Drug: Placebo for moxifloxacin |
| 004 | Experimental | TMC435 2 capsules of 75 mg and 2 capsules of 100 mg once daily for 7 days in Treatment B Receives: Drug: TMC435 |
| 005 | Other | Placebo for TMC435 4 placebo capsules once daily for 7 days in Treatment C Receives: Drug: Placebo for TMC435 |
| 006 | Other | Moxifloxacin 1 tablet of 400 mg on Day 7 of Treatment C Receives: Drug: Moxifloxacin |
| 007 | Placebo comparator | Placebo for TMC435 4 placebo capsules once daily for 7 days in Treatment D Receives: Drug: Placebo for TMC435 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in QT/QTc interval for TMC435 therapeutic dose versus placebo
Measured: 24-hour measurement on Day 7 of Treatment Session A and D
Change in QT/QTc interval for TMC435 supratherapeutic dose versus placebo
Measured: 24-hour measurement on Day 7 of Treatment Session B and D
Secondary outcomes (9)
RR interval, HR, PR interval, QRS interval and ECG morphology
Measured: 1-hour predose measurement on Day 1 of every treatment session
RR interval, HR, PR interval, QRS interval and ECG morphology
Measured: 24-hour measurement on Day 7 of every treatment session
Pharmacokinetics of 150 mg TMC435 once daily for 7 days
Measured: 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
Pharmacokinetics of 350 mg TMC435 once daily for 7 days
Measured: 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
Changes from baseline for electrocardiogram (ECG) and physical examination
Measured: 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
Number of participants with adverse events and severity of adverse events
Measured: From signing of informed consent onwards until last trial-related visit
Changes from baseline and percentage of subjects with abnormal values for laboratory parameters
Measured: At screening, on Days -1, 1, 5, 8 of all treatment sessions and at the follow-up visits
Changes from baseline and percentage of subjects with abnormal values for pulse and blood pressure
Measured: 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
Difference of QTc between moxifloxacin treatment and placebo treatment as a measure for trial sensitivity
Measured: On Day 7 of Treatment C and D, at the 2, 3, 4 and 5 hour timepoints
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tibotec Pharmaceuticals Clinical Trial, Study director, Tibotec Pharmaceutical Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01269294
- Sponsor's protocol ID
- CR017491
- Other IDs
- TMC435-TiDP16-C117
- Status last verified
- May 2013
- First submitted
- 30 Dec 2010
- Last updated
- 6 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01269294
- Acronym / sponsor ID
- CR017491
- Conditions
- Hepatitis C
- Keywords
- Hepatitis C, TMC435-TiDP16-C117, TMC435-C117, TMC435, HCV, Moxifloxacin, ECG, QT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Jan 2011
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 4 Jan 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 001 | Experimental | Drug: TMC435TMC435 2 capsules of 75 mg once daily for 7 days in Treatment A |
| 002 | Other | Drug: Placebo for TMC435Placebo for TMC435 2 placebo capsules once daily for 7 days in Treatment A |
| 003 | Other | Drug: Placebo for moxifloxacinPlacebo for moxifloxacin 1 placebo tablet on Day 7 of Treatments A B and D |
| 004 | Experimental | Drug: TMC435TMC435 2 capsules of 75 mg and 2 capsules of 100 mg once daily for 7 days in Treatment B |
| 005 | Other | Drug: Placebo for TMC435Placebo for TMC435 4 placebo capsules once daily for 7 days in Treatment C |
| 006 | Other | Drug: MoxifloxacinMoxifloxacin 1 tablet of 400 mg on Day 7 of Treatment C |
| 007 | Placebo comparator | Drug: Placebo for TMC435Placebo for TMC435 4 placebo capsules once daily for 7 days in Treatment D |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMC4352 capsules of 75 mg once daily for 7 days in Treatment A | Drug | 001 |
| Placebo for TMC4354 placebo capsules once daily for 7 days in Treatment C | Drug | 005 |
| TMC4352 capsules of 75 mg and 2 capsules of 100 mg once daily for 7 days in Treatment B | Drug | 004 |
| Placebo for TMC4352 placebo capsules once daily for 7 days in Treatment A | Drug | 002 |
| Moxifloxacin1 tablet of 400 mg on Day 7 of Treatment C | Drug | 006 |
| Placebo for moxifloxacin1 placebo tablet on Day 7 of Treatments A, B and D | Drug | 003 |
| Placebo for TMC4354 placebo capsules once daily for 7 days in Treatment D | Drug | 007 |
Primary outcome
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
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
9 secondary outcomes
RR interval, HR, PR interval, QRS interval and ECG morphology
Time frame: 1-hour predose measurement on Day 1 of every treatment session
RR interval, HR, PR interval, QRS interval and ECG morphology
Time frame: 24-hour measurement on Day 7 of every treatment session
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
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
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
Number of participants with adverse events and severity of adverse events
Time frame: From signing of informed consent onwards until last trial-related visit
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2013.
Related trials for Hepatitis C
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Not yet recruitingObservational study
Elimination of Hepatitis C Virus Among Users of Substances
Hepatitis C in Substance Users
Not yet recruiting
Clinical Study to Evaluate the Performance of the INSTI® HCV Antibody Test for CLIA-Waived Use
HCV Infection
Not yet recruiting
Study to Evaluate the Performance of the INSTI® HCV Antibody Test for Point-of-Care Use in Individuals at Risk for HCV Infection or Presenting With Signs or Symptoms of HCV Infection
HCV Infection
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tibotec Pharmaceuticals Clinical Trial study director
Tibotec Pharmaceutical Limited
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TMC435 and Moxifloxacin in people with Hepatitis C, run by Tibotec Pharmaceuticals, Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2013.