TuberculosisPhase 1NCT02216331
PK Interaction Between Rifapentine or Rifampicin and a Single Dose of TMC207 in Healthy Subjects (TMC207-CL002)
A Phase 1 study testing TMC207, rifapentine and rifampicin in people with Tuberculosis, run by Global Alliance for TB Drug Development at 1 site in United States.
Trial summary
This is a open-label study, 2-treatment, 2-period, single sequence design. Period 1 will examine the pharmacokinetics of TMC207 in the absence of rifapentine or rifampicin. Subjects will receive a single 400-mg dose of TMC207 administered alone on Study Day 1. Read more about this study
- Who is it for?
- Ages 19 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- TMC207, rifapentine and rifampicin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to May 2010
- 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 19 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aged between 19 and 55 years, extremes included.
- Non tobacco/nicotine using (at least 3 months prior to screening).
- Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 32.0 kg/m2, inclusive.
- Informed Consent Form (ICF) signed voluntarily before the first trial-related activity.
- Able to comply with protocol requirements.
- Healthy on the basis of a medical evaluation or history that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, electrocardiogram (ECG), vital signs, and the results of blood biochemistry, and hematology tests and a urinalysis carried out at screening (See Section 6.1).
Who cannot join
- Female, except if postmenopausal since more than 2 years, or post-hysterectomy, or post surgical sterilization, i.e., tubal ligation (without reversal operation) or total hysterectomy.
- 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.
- Any clinically significant (as deemed by the Principle Investigator) history acute illness (resolved within 4 weeks of screening), or presence of cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal (including eating disorders), endocrine, metabolic, immunologic, dermatologic, neurologic, psychological, or psychiatric 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 such as, but not limited to, rash or eruptions, drug allergies, food allergy, dermatitis, eczema, psoriasis, or urticaria. Subjects with a history of skin disease may be enrolled into the study after consultation with the Sponsor Medical Monitor.
- Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication administered in this trial (i.e. rifapentine, rifampicin, and TMC207).
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- Subjects with QTcF [Fredericia correction] interval > 450 msec (based on the average of the triplicate ECGs) at screening (and confirmed by repeat ECG).
- Subjects with any other clinically significant ECG abnormality at screening, such as arrhythmia, ischemia, or evidence of heart failure or with a family history of Long QT Syndrome.
- Use of concomitant medication, including over-the-counter products and dietary supplements, except for ibuprofen and paracetamol up to 7 days before the first dose of trial medication and all prescribed medication must have been discontinued at least 14 days before first intake of trial medication.
- Participation in an investigational drug trial within 60 days prior to the first intake of trial medication.
- Donation of blood or significant loss of blood within 56 days or plasma donation within 7 days preceding the first intake of trial medication.
- Having received TMC207 in a previous trial.
- Positive HIV-1 or HIV-2 test at screening
- Hepatitis A, B, or C infection (confirmed by hepatitis A antibody IgM, hepatitis B surface antigen, or hepatitis C virus antibody, respectively) at screening.
- A positive urine drug test at screening. Urine will be tested to check the current use of alcohol, amphetamines, benzodiazepines, cocaine, cannabinoids, and opioids.
- Subjects with the following laboratory abnormalities at screening as defined by the NIH, NIAID, Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table and in accordance with the normal ranges of the clinical laboratory: Serum creatinine grade 1 or greater (> 1.0 x ULN); Pancreatic lipase grade 1 or greater (> 1.0 x ULN); Hemoglobin grade 1 or greater (≤ 10.5 g/dL); Platelet count grade 1 or greater (≤ 99000/mm3); Absolute neutrophil count grade 1 or greater (≤ 1500/mm3); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (> 1.0 x ULN); Total bilirubin grade 1 or greater (> 1.0 x ULN); Any other toxicity grade 2 or above, including: proteinuria (spot urine) > 1+ and gross hematuria.
Trial locations and contacts
1 site in 1 country.
United States1 site
Celerion (MDS Pharma Services)
Lincoln, Nebraska, 68502
About this study
Official title: A Phase I Open-label Trial to Investigate the Pharmacokinetic Interaction Between Rifapentine or Rifampicin and a Single Dose of TMC207 in Healthy Subjects
This is a open-label study, 2-treatment, 2-period, single sequence design. Period 1 will examine the pharmacokinetics of TMC207 in the absence of rifapentine or rifampicin. Subjects will receive a single 400-mg dose of TMC207 administered alone on Study Day 1. Period 2 will examine the effects of repeated doses of either rifapentine or rifampicin on TMC207 pharmacokinetics and will begin on Study Day 20. During Period 2, subjects will receive 22 daily doses of either 600 mg rifapentine or rifampicin from Study Day 20 through Study Day 41. A single 400-mg dose of TMC207 will be administered on Study Day 29. Subjects will be confined to the clinic from Study Day-1 to Study Day 2 in the morning of Period 1, and Study Day 19 to Study Day 30 in the morning of Period 2. The study hypothesis is to determine whether Rifapentine affects the pharmacokinetics of TMC207 as measured by effects on Cmax and AUC(0-t) to a lesser degree than rifampicin.
- Conditions
- Tuberculosis
- Being tested
- TMC207, rifapentine, rifampicin
- Keywords
- tuberculosis, PK, TMC207, bedaquiline, rifapentine, rifampicin, drug drug interaction
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC207Drug
Also called bedaquiline
This is a two group, 2 period study design with both groups in the first period receiving TMC207 alone, followed by one group in the second period receiving TMC207 in the presence of dosing with rifapentine and the other group receiving TMC207 in the presence of dosing with rifampicin. All treatments details specified under "Arms" description.
rifapentineDrug
rifampicinDrug
| Study group | Role | What they receive |
|---|---|---|
| Group 1 TMC207 alone | Experimental | A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 1. Receives: Drug: TMC207 |
| Group 1 TMC207 and rifapentine | Experimental | A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 29 and 600 mg of rifapentine administered as 4 tablets of 150 mg per tablet on each of Study Days 20-41. Receives: Drug: TMC207; Drug: rifapentine |
| Group 2 TMC207 alone | Experimental | A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 1. Receives: Drug: TMC207 |
| Group 2 TMC207 and rifampicin | Experimental | A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 29 and 600 mg of rifampicin administered as 4 capsules of 150 mg per capsule on each of Study Days 20-41. Receives: Drug: TMC207; Drug: rifampicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed TMC207 concentration in ng/mL [Cmax] between Groups 1 and 2
To evaluate the relative effect of rifapentine and rifampicin on Cmax of TMC207, the Cmax of TMC207 was compared between Group 1 (rifapentine) and Group 2 (rifampicin) using analysis of variance model (ANOVA).
Measured: through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration-time curve in ng*hr/mL [AUC0-t] between Groups 1 and 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-t of TMC207, the AUC0-t of TMC207 was compared between Group 1 (rifapentine) and Group 2 (rifampicin) using analysis of variance model (ANOVA).
Measured: through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration cuve from time zero to infinity in ng*hr/mL [AUC0-inf] between Groups 1 and 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-inf of TMC207, the AUC0-inf of TMC207 was compared between Group 1 (rifapentine) and Group 2 (rifampicin) using analysis of variance model (ANOVA).
Measured: through 336 hours post dosing in Period 1 and Period 2
Secondary outcomes (3)
Maximum observed TMC207 concentration in ng/mL [Cmax] within treatment groups between Periods 1 and 2
To evaluate the relative effect of rifapentine and rifampicin on Cmax of TMC207, the Cmax of TMC207 was compared between the TMC207 + rifapentine treatment (Group 1) or rifampicin (Group 2) and TMC207 alone using analysis of variance model (ANOVA).
Measured: through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration-time curve in ng*hr/mL [AUC0-t] within treatment groups between Periods 1 and 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-t of TMC207, the AUC0-t of TMC207 was compared between the TMC207 + rifapentine treatment (Group 1) or rifampicin (Group 2) and TMC207 alone using analysis of variance model (ANOVA).
Measured: through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration cuve from time zero to infinity in ng*hr/mL [AUC0-inf] within treatment groups between Periods 1 and 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-inf of TMC207, the AUC0-inf of TMC207 was compared between the TMC207 + rifapentine treatment (Group 1) or rifampicin (Group 2) and TMC207 alone using analysis of variance model (ANOVA).
Measured: through 336 hours post dosing in Period 1 and Period 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2014 (estimated)
- Study startMar 2010
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Scott Rasmussen, MD, Principal investigator, Celerion (MDS Pharma Services)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02216331
- Sponsor's protocol ID
- TMC207-CL002
- Status last verified
- Sep 2019
- First submitted
- 12 Aug 2014
- Last updated
- 6 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Winter H, Egizi E, Murray S, Erondu N, Ginsberg A, Rouse DJ, Severynse-Stevens D, Pauli E. Evaluation of the pharmacokinetic interaction between repeated doses of rifapentine or rifampin and a single dose of bedaquiline in healthy adult subjects. Antimicrob Agents Chemother. 2015 Feb;59(2):1219-24. doi: 10.1128/AAC.04171-14. Epub 2014 Dec 15.
PubMed 25512422
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-label Trial to Investigate the Pharmacokinetic Interaction Between Rifapentine or Rifampicin and a Single Dose of TMC207 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02216331
- Acronym / sponsor ID
- TMC207-CL002
- Conditions
- Tuberculosis
- Keywords
- tuberculosis, PK, TMC207, bedaquiline, rifapentine, rifampicin, drug drug interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Global Alliance for TB Drug DevelopmentUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 13 Aug 2014 (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.
This is a open-label study, 2-treatment, 2-period, single sequence design. Period 1 will examine the pharmacokinetics of TMC207 in the absence of rifapentine or rifampicin. Subjects will receive a single 400-mg dose of TMC207 administered alone on Study Day 1. Period 2 will examine the effects of repeated doses of either rifapentine or rifampicin on TMC207 pharmacokinetics and will begin on Study Day 20. During Period 2, subjects will receive 22 daily doses of either 600 mg rifapentine or rifampicin from Study Day 20 through Study Day 41. A single 400-mg dose of TMC207 will be administered on Study Day 29. Subjects will be confined to the clinic from Study Day-1 to Study Day 2 in the morning of Period 1, and Study Day 19 to Study Day 30 in the morning of Period 2. The study hypothesis is to determine whether Rifapentine affects the pharmacokinetics of TMC207 as measured by effects on Cmax and AUC(0-t) to a lesser degree than rifampicin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 TMC207 alone | Experimental | Drug: TMC207A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 1. |
| Group 1 TMC207 and rifapentine | Experimental | Drug: TMC207, Drug: rifapentineA single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 29 and 600 mg of rifapentine administered as 4 tablets of 150 mg per tablet on each of Study Days 20-41. |
| Group 2 TMC207 alone | Experimental | Drug: TMC207A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 1. |
| Group 2 TMC207 and rifampicin | Experimental | Drug: TMC207, Drug: rifampicinA single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 29 and 600 mg of rifampicin administered as 4 capsules of 150 mg per capsule on each of Study Days 20-41. |
Who may qualify
- Ages
- 19 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Aged between 19 and 55 years, extremes included.
- Non tobacco/nicotine using (at least 3 months prior to screening).
- Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 32.0 kg/m2, inclusive.
- Informed Consent Form (ICF) signed voluntarily before the first trial-related activity.
- Able to comply with protocol requirements.
Key exclusion criteria (16 listed)
- Female, except if postmenopausal since more than 2 years, or post-hysterectomy, or post surgical sterilization, i.e., tubal ligation (without reversal operation) or total hysterectomy.
- 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.
- Any clinically significant (as deemed by the Principle Investigator) history acute illness (resolved within 4 weeks of screening), or presence of cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal (including eating disorders), endocrine, metabolic, immunologic, dermatologic, neurologic, psychological, or psychiatric 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 such as, but not limited to, rash or eruptions, drug allergies, food allergy, dermatitis, eczema, psoriasis, or urticaria. Subjects with a history of skin disease may be enrolled into the study after consultation with the Sponsor Medical Monitor.
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 |
|---|---|---|
| TMC207Also: bedaquilineThis is a two group, 2 period study design with both groups in the first period receiving TMC207 alone, followed by one group in the second period receiving TMC207 in the presence of dosing with rifapentine and the other group receiving TMC207 in the presence of dosing with rifampicin. All treatments details specified under "Arms" description. | Drug | Group 1 TMC207 alone, Group 1 TMC207 and rifapentine, Group 2 TMC207 alone, Group 2 TMC207 and rifampicin |
| rifapentine | Drug | Group 1 TMC207 and rifapentine |
| rifampicin | Drug | Group 2 TMC207 and rifampicin |
Primary outcome
Maximum observed TMC207 concentration in ng/mL [Cmax] between Groups 1 and 2
Time frame: through 336 hours post dosing in Period 1 and Period 2
To evaluate the relative effect of rifapentine and rifampicin on Cmax of TMC207, the Cmax of TMC207 was compared between Group 1 (rifapentine) and Group 2 (rifampicin) using analysis of variance model (ANOVA).
Area under the TMC207 concentration-time curve in ng*hr/mL [AUC0-t] between Groups 1 and 2
Time frame: through 336 hours post dosing in Period 1 and Period 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-t of TMC207, the AUC0-t of TMC207 was compared between Group 1 (rifapentine) and Group 2 (rifampicin) using analysis of variance model (ANOVA).
Area under the TMC207 concentration cuve from time zero to infinity in ng*hr/mL [AUC0-inf] between Groups 1 and 2
Time frame: through 336 hours post dosing in Period 1 and Period 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-inf of TMC207, the AUC0-inf of TMC207 was compared between Group 1 (rifapentine) and Group 2 (rifampicin) using analysis of variance model (ANOVA).
3 secondary outcomes
Maximum observed TMC207 concentration in ng/mL [Cmax] within treatment groups between Periods 1 and 2
Time frame: through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration-time curve in ng*hr/mL [AUC0-t] within treatment groups between Periods 1 and 2
Time frame: through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration cuve from time zero to infinity in ng*hr/mL [AUC0-inf] within treatment groups between Periods 1 and 2
Time frame: through 336 hours post dosing in Period 1 and Period 2
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 Sep 2019.
- Derived from this study: PubMed 25512422Winter H, Egizi E, Murray S, Erondu N, Ginsberg A, Rouse DJ, Severynse-Stevens D, Pauli E. Evaluation of the pharmacokinetic interaction between repeated doses of rifapentine or rifampin and a single dose of bedaquiline in healthy adult subjects. Antimicrob Agents Chemother. 2015 Feb;59(2):1219-24. doi: 10.1128/AAC.04171-14. Epub 2014 Dec 15.
- Global Alliance for TB Drug Development websiteLink provided by the sponsor.
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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.
Scott Rasmussen, MD principal investigator
Celerion (MDS Pharma Services)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TMC207, rifapentine and rifampicin in people with Tuberculosis, run by Global Alliance for TB Drug Development at 1 site in United States.
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 6 inclusion and 16 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 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Maximum observed TMC207 concentration in ng/mL [Cmax] between Groups 1 and 2 (time frame: through 336 hours post dosing in Period 1 and Period 2). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02216331, which also lists 1 linked publication.
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 Sep 2019.