Hepatitis CPhase 1NCT00741169
TMC435350-TiDP16-C105: Phase I, 3-way Crossover, Drug-drug Interaction Between TMC435350 and Rifampin After Multiple Dosing.
A Phase 1 study testing TMC435350, Rifampin and TMC435350+rifampin in people with Hepatitis C and HCV, run by Tibotec Pharmaceuticals, Ireland.
Trial summary
The purpose of this study is to assess the interactions seen when somebody doses with TMC435350 and Rifampin (commercial form of antibiotic). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C, HCV, Tuberculosis
- What is being tested?
- TMC435350, Rifampin and TMC435350+rifampin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- No sites listed yet
- Study dates
- Jun 2008to Dec 2008
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Volunteers must meet all of the following inclusion criteria: Non smoking for at least 3 months prior to selection, Normal weight as defined by a body mass index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 32.0 kg/m2, extremes included), Informed Consent Form (ICF) signed voluntarily before the first trial related activity, Able to comply with protocol requirements, Normal 12-lead electrocardiogram (ECG) (in triplicate) at screening including: Normal sinus rhythm (heart rate [HR] between 40 and 100 bpm), QTc interval = 450 ms, QRS interval < 120 ms, PR interval = 220 ms
- Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, vital signs, and the results of blood biochemistry, and hematology tests and a urinalysis carried out at screening.
Who cannot join
- Past history of heart arrhythmias (extrasystole, tachycardia at rest) or having baseline prolongation of QTc interval > 450 ms
- history of risk factors for Torsade de Pointes syndrome (hypokalemia, family history of long QT syndrome)
- Female, except if postmenopausal since more than 2 years, or posthysterectomy, or post tubal ligation (without reversal operation)
- History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the investigator's opinion would compromise subject's safety and/or compliance with the trial procedures
- Hepatitis A, B, or C infection (confirmed by hepatitis A antibody, hepatitis B surface antigen, or hepatitis C virus antibody, respectively) or human immunodeficiency virus - type 1 (HIV-1) or HIV-2 infection at screening
- A positive urine drug test at screening
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- Currently active or underlying gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease
- Currently significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability
- Any history of significant skin disease.
About this study
Official title: Phase I, Open-label, 3-way Crossover Trial in Healthy Volunteers to Determine the Drug-drug Interaction Between TMC435350 and Rifampin After Multiple Dosing.
The purpose of this study is to assess the interactions seen when somebody doses with TMC435350 and Rifampin (commercial form of antibiotic).
Read the detailed description
This is a Phase I, open-label, randomized, 3-way crossover trial in 18 healthy volunteers to investigate the potential drug-drug interaction between rifampin and TMC435350. TMC435350 is a protease inhibitor in development for treatment of chronic HCV infection. The goal is to assess the PK and safety data generated during 3 in-patients sessions. At each session the volunteer will receive one of 3 treatments. Rifampin is a medication commonly given to patients with Mycobacterium infections such as tuberculosis. Some patients have both chronic HCV and tuberculosis, therefore it is necessary to know how the medications will affect each other when they are taken together. Treatment A: TMC435350 200 mg q.d. for 7 days. Treatment B: rifampin 600 mg q.d. for 7 days. Treatment C: the combination of TMC435350 200 mg q.d. + rifampin 600 mg q.d. for 7 days. There will be a washout period of at least 10 days between subsequent sessions. Day 8 of a treatment session is the first day of the washout period. Full pharmacokinetic profiles of TMC435350 will be determined on Day 7 of Treatments A and C. Full pharmacokinetic profiles of rifampin and its active metabolite 25-deacetyl rifampin will be determined on Day 7 of Treatments B and C. Safety and tolerability will be monitored continuously throughout the trial. Volunteers will receive the dose regimens in Treatments A, B, C: Treatment A: TMC435350 200 mg q.d. for 7 days. Treatment B: rifampin 600 mg q.d. for 7 days, Treatment C: the combination of TMC435350 200 mg+rifampin 600 mg both q.d. for 7 days. The volunteers will enter the testing facility the night before the first dosing in each session (on Day -1 = one day before the first dosing) and stay in the testing facility until 72 hours after the last intake of medication on Day (10).
- Conditions
- Hepatitis C, HCV, Tuberculosis, Rifampin, Pharmacokinetics
- Being tested
- TMC435350, Rifampin, TMC435350+rifampin
- Keywords
- TMC435350-TiDP16-C105, TMC435350-C105, Hepatitis C, HCV, Rifampin
- Medical subject headings
- Hepatitis C, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC435350Drug
200 mg taken by mouth once daily for 7 days
RifampinDrug
600 mg taken by mouth once daily for 7 days
TMC435350+rifampinDrug
The combination of TMC435350 200 mg + rifampin 600 mg both taken by mouth once daily for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Sequence ABC | Experimental | Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence will consist of Treatment A (TMC435350 200 mg once daily for 7 days), Treatment B (rifampin 600 mg once daily for 7 days), and Treatment C (TMC435350 200 mg once daily+rifampin 600 mg once daily for 7 days). Participants will receive 1 treatment (A, B, or C) during each treatment session. There will be 3 treatment sessions, each treatment session will be separated by 10 days. Receives: Drug: TMC435350; Drug: Rifampin; Drug: TMC435350+rifampin |
| Treatment Sequence BCA | Experimental | Not described Receives: Drug: TMC435350; Drug: Rifampin; Drug: TMC435350+rifampin |
| Treatment Sequence CAB | Experimental | Not described Receives: Drug: TMC435350; Drug: Rifampin; Drug: TMC435350+rifampin |
| Treatment sequence CBA | Experimental | Not described Receives: Drug: TMC435350; Drug: Rifampin; Drug: TMC435350+rifampin |
| Treatment Sequence BAC | Experimental | Not described Receives: Drug: TMC435350; Drug: Rifampin; Drug: TMC435350+rifampin |
| Treatment Sequence ACB | Experimental | Not described Receives: Drug: TMC435350; Drug: Rifampin; Drug: TMC435350+rifampin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic (PK) profile of TMC435350
The following PK parameters will be assessed: C0h on Day 7 of Treatments A and C; and C0h, Cmin, Cmax, tmax, AUC24h, Css,av, FI, λz, t1/2term, Ratio Cmin test/ref, Ratio C0h test/ref, Ratio Cmax test/ref, and Ratio AUC24h test/ref.
Measured: On Day 1, 2, 4, 6, and 7 of Treatments A and C
Pharmacokinetic (PK) profile of rifampin and 25-deacetylrifampin
The PK parameter of C0h will be assessed on Day 1, 2, 4 and 6 of Treatments B and C, and the PK parameters of C0h, Cmin, Cmax, tmax, AUC24h, Css,av, FI, λz, t1/2term, Ratio Cmin test/ref, Ratio C0h test/ref , Ratio Cmax test/ref , Ratio AUC24h test/ref on Day 7 of Treatments B and C.
Measured: On Day 1, 2, 4, 6, and 7 of Treatments B and C
Secondary outcomes (1)
The number of participants reporting adverse events as a measure of safety and tolerability.
Measured: Up to 30 to 35 days after the last intake of study drug.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2008 (estimated)
- Study startJun 2008
- Primary completionDec 2008
- Study completionDec 2008
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
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tibotec Pharmaceuticals Limited Clinical Trial, Study director, Tibotec Pharmaceutical Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00741169
- Sponsor's protocol ID
- CR015412
- Status last verified
- Apr 2013
- First submitted
- 22 Aug 2008
- Last updated
- 18 Apr 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Open-label, 3-way Crossover Trial in Healthy Volunteers to Determine the Drug-drug Interaction Between TMC435350 and Rifampin After Multiple Dosing.
- ClinicalTrials.gov ID
- NCT00741169
- Acronym / sponsor ID
- CR015412
- Conditions
- Hepatitis C, HCV, Tuberculosis, Rifampin, Pharmacokinetics
- Keywords
- TMC435350-TiDP16-C105, TMC435350-C105, Hepatitis C, HCV, Rifampin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Jun 2008
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 26 Aug 2008 (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 assess the interactions seen when somebody doses with TMC435350 and Rifampin (commercial form of antibiotic).
Detailed description
This is a Phase I, open-label, randomized, 3-way crossover trial in 18 healthy volunteers to investigate the potential drug-drug interaction between rifampin and TMC435350. TMC435350 is a protease inhibitor in development for treatment of chronic HCV infection. The goal is to assess the PK and safety data generated during 3 in-patients sessions. At each session the volunteer will receive one of 3 treatments. Rifampin is a medication commonly given to patients with Mycobacterium infections such as tuberculosis. Some patients have both chronic HCV and tuberculosis, therefore it is necessary to know how the medications will affect each other when they are taken together. Treatment A: TMC435350 200 mg q.d. for 7 days. Treatment B: rifampin 600 mg q.d. for 7 days. Treatment C: the combination of TMC435350 200 mg q.d. + rifampin 600 mg q.d. for 7 days. There will be a washout period of at least 10 days between subsequent sessions. Day 8 of a treatment session is the first day of the washout period. Full pharmacokinetic profiles of TMC435350 will be determined on Day 7 of Treatments A and C. Full pharmacokinetic profiles of rifampin and its active metabolite 25-deacetyl rifampin will be determined on Day 7 of Treatments B and C. Safety and tolerability will be monitored continuously throughout the trial. Volunteers will receive the dose regimens in Treatments A, B, C: Treatment A: TMC435350 200 mg q.d. for 7 days. Treatment B: rifampin 600 mg q.d. for 7 days, Treatment C: the combination of TMC435350 200 mg+rifampin 600 mg both q.d. for 7 days. The volunteers will enter the testing facility the night before the first dosing in each session (on Day -1 = one day before the first dosing) and stay in the testing facility until 72 hours after the last intake of medication on Day (10).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Treatment Sequence ABC | Experimental | Drug: TMC435350, Drug: Rifampin, Drug: TMC435350+rifampinParticipants will be randomized to each of the 6 different treatment sequences. Each treatment sequence will consist of Treatment A (TMC435350 200 mg once daily for 7 days), Treatment B (rifampin 600 mg once daily for 7 days), and Treatment C (TMC435350 200 mg once daily+rifampin 600 mg once daily for 7 days). Participants will receive 1 treatment (A, B, or C) during each treatment session. There will be 3 treatment sessions, each treatment session will be separated by 10 days. |
| Treatment Sequence BCA | Experimental | Drug: TMC435350, Drug: Rifampin, Drug: TMC435350+rifampin |
| Treatment Sequence CAB | Experimental | Drug: TMC435350, Drug: Rifampin, Drug: TMC435350+rifampin |
| Treatment sequence CBA | Experimental | Drug: TMC435350, Drug: Rifampin, Drug: TMC435350+rifampin |
| Treatment Sequence BAC | Experimental | Drug: TMC435350, Drug: Rifampin, Drug: TMC435350+rifampin |
| Treatment Sequence ACB | Experimental | Drug: TMC435350, Drug: Rifampin, Drug: TMC435350+rifampin |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Volunteers must meet all of the following inclusion criteria: Non smoking for at least 3 months prior to selection, Normal weight as defined by a body mass index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 32.0 kg/m2, extremes included), Informed Consent Form (ICF) signed voluntarily before the first trial related activity, Able to comply with protocol requirements, Normal 12-lead electrocardiogram (ECG) (in triplicate) at screening including: Normal sinus rhythm (heart rate [HR] between 40 and 100 bpm), QTc interval = 450 ms, QRS interval < 120 ms, PR interval = 220 ms
- Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, vital signs, and the results of blood biochemistry, and hematology tests and a urinalysis carried out at screening.
Key exclusion criteria (9 listed)
- Past history of heart arrhythmias (extrasystole, tachycardia at rest) or having baseline prolongation of QTc interval > 450 ms
- history of risk factors for Torsade de Pointes syndrome (hypokalemia, family history of long QT syndrome)
- Female, except if postmenopausal since more than 2 years, or posthysterectomy, or post tubal ligation (without reversal operation)
- History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the investigator's opinion would compromise subject's safety and/or compliance with the trial procedures
- Hepatitis A, B, or C infection (confirmed by hepatitis A antibody, hepatitis B surface antigen, or hepatitis C virus antibody, respectively) or human immunodeficiency virus - type 1 (HIV-1) or HIV-2 infection at screening
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 |
|---|---|---|
| TMC435350200 mg taken by mouth once daily for 7 days | Drug | Treatment Sequence ABC, Treatment Sequence ACB, Treatment Sequence BAC, Treatment Sequence BCA, Treatment Sequence CAB, Treatment sequence CBA |
| Rifampin600 mg taken by mouth once daily for 7 days | Drug | Treatment Sequence ABC, Treatment Sequence ACB, Treatment Sequence BAC, Treatment Sequence BCA, Treatment Sequence CAB, Treatment sequence CBA |
| TMC435350+rifampinThe combination of TMC435350 200 mg + rifampin 600 mg both taken by mouth once daily for 7 days. | Drug | Treatment Sequence ABC, Treatment Sequence ACB, Treatment Sequence BAC, Treatment Sequence BCA, Treatment Sequence CAB, Treatment sequence CBA |
Primary outcome
Pharmacokinetic (PK) profile of TMC435350
Time frame: On Day 1, 2, 4, 6, and 7 of Treatments A and C
The following PK parameters will be assessed: C0h on Day 7 of Treatments A and C; and C0h, Cmin, Cmax, tmax, AUC24h, Css,av, FI, λz, t1/2term, Ratio Cmin test/ref, Ratio C0h test/ref, Ratio Cmax test/ref, and Ratio AUC24h test/ref.
Pharmacokinetic (PK) profile of rifampin and 25-deacetylrifampin
Time frame: On Day 1, 2, 4, 6, and 7 of Treatments B and C
The PK parameter of C0h will be assessed on Day 1, 2, 4 and 6 of Treatments B and C, and the PK parameters of C0h, Cmin, Cmax, tmax, AUC24h, Css,av, FI, λz, t1/2term, Ratio Cmin test/ref, Ratio C0h test/ref , Ratio Cmax test/ref , Ratio AUC24h test/ref on Day 7 of Treatments B and C.
1 secondary outcome
The number of participants reporting adverse events as a measure of safety and tolerability.
Time frame: Up to 30 to 35 days after the last intake of study drug.
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 18 Apr 2013.
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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 Limited Clinical Trial study director
Tibotec Pharmaceutical Limited
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TMC435350, Rifampin and TMC435350+rifampin in people with Hepatitis C and HCV, 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 2 inclusion and 9 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 18 Apr 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. 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?
Pharmacokinetic (PK) profile of TMC435350 (time frame: On Day 1, 2, 4, 6, and 7 of Treatments A and C). 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 18 Apr 2013.