TuberculosisPhase 1NCT01341184
TMC207 +/- Rifabutin/Rifampin
A Phase 1 study testing Rifabutin, Rifampin and TMC207 in people with Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Evaluation of effect of rifampin or rifabutin on single dose PK of TMC207 in healthy volunteers Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Rifabutin, Rifampin and TMC207
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Oct 2011to 23 May 2012
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- -Aged between 18 and 45 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 <35.0 kg/m^2 -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, ophthalmologic exam, the results of blood biochemistry, and hematology tests, and a urinalysis carried out at screening (See Section 7.2). -Subjects will be enrolled in this study only if they have undergone vasectomy/complete hysterectomy, tubal ligation, or other sterilizing procedure, or the subject is a post-menopausal woman for more than two years, or if sexually active subjects agree to use two of the following forms of adequate contraception during the study and for 12 weeks after the final dose: abstinence, condoms with or without spermicide gel, diaphragm with spermicide gel, hormonal or non-hormonal intrauterine device, oral contraceptive pills, and depot progesterone injections. If a subject is usually not sexually active but becomes active, the subject and his or her partner must use two of the listed contraceptive methods.
Who cannot join
- Medical History -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 Principal Investigator) history of acute illness (resolved within 4 weeks of screening), asthma, 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., rifabutin, rifampin, and TMC207). -Subjects with QTcB [Bazett correction] interval > 450ms at screening -Subjects with any other clinically significant Electrocardiogram (ECG) abnormality at screening, such as arrhythmia, ischemia, or evidence of heart failure or with a family history of Long QT Syndrome. -History or evidence of ophthalmologic diseases except for routine corrected hyperopia, myopia, and presbyopia. -Recent history (within past 30 days) of vertigo/nausea. Specific Treatments -Current use of any azole antifungal agent -Use of concomitant medication, including over-the-counter products and dietary supplements, without approval from study staff. Subjects will be treated based on symptom presentation, with the exception of medications that affect p450 and 3a metabolic pathways (refer to the MOP for a list of acceptable medications). During outpatient time periods, subjects will be required to discuss with the study staff and receive approval before self-administering any medication. After gaining approval, subjects will also be asked to record any medication taken during outpatient time periods in a provided log. -Participation in an investigational drug trial within 60 days prior to the first intake of trial medication and during the duration of the study. -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. Based on Laboratory Abnormalities -Positive HIV-1 or HIV-2 test by Enzyme-linked immunosorbent assay (ELISA) 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 amphetamines, benzodiazepines, cocaine, cannabinoids, and opioids; along with serum alcohol level. -Subjects with the following laboratory abnormalities at screening as defined by the National Institute of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table (Appendix C) and in accordance with the normal ranges of the clinical laboratory: a.Serum creatinine grade 1 or greater [> 1.0 x Upper limit of lab normal range (ULN)], b.Pancreatic lipase grade 1 or greater (> 1.0 x ULN), c.Hemoglobin grade 1 or greater (</= 10.5 g/dL), d.Platelet count grade 1 or greater (</= 99000/mm^3), e.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (> 1.0 x ULN), f.Total bilirubin grade 1 or greater (> 1.0 x ULN), g.Creatine kinase grade 1 or greater (>1.0 x ULN), h.Troponin grade 1 or greater (1.0 x UNL), or i.Any other toxicity grade 2 or above, including: proteinuria (spot urine) > 1+ and gross hematuria. For the second dose of TMC207, any other toxicity grade 3 or above, including: proteinuria (spot urine) > 1+ and gross hematuria
Trial locations and contacts
1 site in 1 country.
United States1 site
Case Western Reserve University - Case Medical Center - Infectious Disease & HIV Medicine
Cleveland, Ohio, 44106-1716
About this study
Official title: A Phase I Open-Label Trial To Investigate the Pharmacokinetic Interaction Between Rifabutin Or Rifampin And A Single Dose Of TMC207 In Healthy Subjects
Evaluation of effect of rifampin or rifabutin on single dose PK of TMC207 in healthy volunteers
Read the detailed description
32 (16 per treatment group) healthy male or female subjects, 18 - 45 years old will be enrolled.Subjects will receive two single oral doses of 400mg TMC207, first on Study Day 1 followed by a 28-day wash-out, the second on Study Day 29. On Study Day 28, any abnormal safety labs will be reviewed by study physician and be determined not to meet the exclusion criteria before administration of the second dose of TMC207. Rifabutin 300mg (Group 1) or rifampin 600mg (Group 2) will be administered once daily during Period 2 from Study Day 20 through Study Day 41. The primary endpoint for the study (pharmacokinetics, safety and tolerability of TMC207 (and its M2 metabolite) will be determined on the final study visit, Day 57 (28 days after the last TMC207 dose in Period 2).
- Conditions
- Tuberculosis
- Being tested
- Rifabutin, Rifampin, TMC207
- Keywords
- rifabutin, rifampin, TMC207, tuberculosis
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifabutinDrug
Rifabutin 300 mg orally on days 20-41
RifampinDrug
Rifampin 600 mg orally on days 20-41
TMC207Drug
TMC207 400 mg orally on days 1 and 29
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | 16 subjects: TMC207 400mg orally on days 1 and 29, rifabutin 300mg orally, every day on day 20-41 Receives: Drug: Rifabutin; Drug: TMC207 |
| Group 2 | Experimental | 16 subjects: TMC207 400mg orally on days 1 and 29, rifampin 600mg orally, every day on day 20-41 Receives: Drug: Rifampin; Drug: TMC207 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic profiles determined for Rifabutin + desacetyl rifabutin
Measured: Day 27-Day 30, Day 35 & Day 41
Pharmacokinetic profiles determined for Rifampin + desacetyl rifampin
Measured: Day 27-Day 30, Day 35 & Day 41
Pharmacokinetic profiles for TMC207 and M2
Measured: Day 1 - Day 15
Pharmacokinetic profiles for TMC207 and M2 in combination with steady-state rifabutin (Group 1)
Measured: Day 29 - Day 41
Pharmacokinetic profiles for TMC207 and M2 in combination with steady-state rifampin (Group 2)
Measured: Day 29 - Day 41
Safety of TMC207
Measured: Over 60 days
Tolerability of TMC207
Measured: Over 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2011 (estimated)
- Study start21 Oct 2011
- Primary completion23 May 2012
- Study completion23 May 2012
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.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- 33 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01341184
- Sponsor's protocol ID
- 10-0043
- Other IDs
- HHSN272201500007I
- Status last verified
- 14 Apr 2017
- First submitted
- 7 Apr 2011
- Last updated
- 21 Apr 2017
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Healan AM, Griffiss JM, Proskin HM, O'Riordan MA, Gray WA, Salata RA, Blumer JL. Impact of Rifabutin or Rifampin on Bedaquiline Safety, Tolerability, and Pharmacokinetics Assessed in a Randomized Clinical Trial with Healthy Adult Volunteers. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e00855-17. doi: 10.1128/AAC.00855-17. Print 2018 Jan.
PubMed 29061739
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2017. 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 Rifabutin Or Rifampin And A Single Dose Of TMC207 In Healthy Subjects
- ClinicalTrials.gov ID
- NCT01341184
- Acronym / sponsor ID
- 10-0043
- Conditions
- Tuberculosis
- Keywords
- rifabutin, rifampin, TMC207, tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 21 Oct 2011 (actual)
- Primary completion
- 23 May 2012 (actual)
- Study completion
- 23 May 2012 (actual)
- First posted
- 25 Apr 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.
Evaluation of effect of rifampin or rifabutin on single dose PK of TMC207 in healthy volunteers
Detailed description
32 (16 per treatment group) healthy male or female subjects, 18 - 45 years old will be enrolled.Subjects will receive two single oral doses of 400mg TMC207, first on Study Day 1 followed by a 28-day wash-out, the second on Study Day 29. On Study Day 28, any abnormal safety labs will be reviewed by study physician and be determined not to meet the exclusion criteria before administration of the second dose of TMC207. Rifabutin 300mg (Group 1) or rifampin 600mg (Group 2) will be administered once daily during Period 2 from Study Day 20 through Study Day 41. The primary endpoint for the study (pharmacokinetics, safety and tolerability of TMC207 (and its M2 metabolite) will be determined on the final study visit, Day 57 (28 days after the last TMC207 dose in Period 2).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Rifabutin, Drug: TMC20716 subjects: TMC207 400mg orally on days 1 and 29, rifabutin 300mg orally, every day on day 20-41 |
| Group 2 | Experimental | Drug: Rifampin, Drug: TMC20716 subjects: TMC207 400mg orally on days 1 and 29, rifampin 600mg orally, every day on day 20-41 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- -Aged between 18 and 45 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 <35.0 kg/m^2 -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, ophthalmologic exam, the results of blood biochemistry, and hematology tests, and a urinalysis carried out at screening (See Section 7.2). -Subjects will be enrolled in this study only if they have undergone vasectomy/complete hysterectomy, tubal ligation, or other sterilizing procedure, or the subject is a post-menopausal woman for more than two years, or if sexually active subjects agree to use two of the following forms of adequate contraception during the study and for 12 weeks after the final dose: abstinence, condoms with or without spermicide gel, diaphragm with spermicide gel, hormonal or non-hormonal intrauterine device, oral contraceptive pills, and depot progesterone injections. If a subject is usually not sexually active but becomes active, the subject and his or her partner must use two of the listed contraceptive methods.
Key exclusion criteria (1 listed)
- Medical History -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 Principal Investigator) history of acute illness (resolved within 4 weeks of screening), asthma, 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., rifabutin, rifampin, and TMC207). -Subjects with QTcB [Bazett correction] interval > 450ms at screening -Subjects with any other clinically significant Electrocardiogram (ECG) abnormality at screening, such as arrhythmia, ischemia, or evidence of heart failure or with a family history of Long QT Syndrome. -History or evidence of ophthalmologic diseases except for routine corrected hyperopia, myopia, and presbyopia. -Recent history (within past 30 days) of vertigo/nausea. Specific Treatments -Current use of any azole antifungal agent -Use of concomitant medication, including over-the-counter products and dietary supplements, without approval from study staff. Subjects will be treated based on symptom presentation, with the exception of medications that affect p450 and 3a metabolic pathways (refer to the MOP for a list of acceptable medications). During outpatient time periods, subjects will be required to discuss with the study staff and receive approval before self-administering any medication. After gaining approval, subjects will also be asked to record any medication taken during outpatient time periods in a provided log. -Participation in an investigational drug trial within 60 days prior to the first intake of trial medication and during the duration of the study. -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. Based on Laboratory Abnormalities -Positive HIV-1 or HIV-2 test by Enzyme-linked immunosorbent assay (ELISA) 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 amphetamines, benzodiazepines, cocaine, cannabinoids, and opioids; along with serum alcohol level. -Subjects with the following laboratory abnormalities at screening as defined by the National Institute of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table (Appendix C) and in accordance with the normal ranges of the clinical laboratory: a.Serum creatinine grade 1 or greater [> 1.0 x Upper limit of lab normal range (ULN)], b.Pancreatic lipase grade 1 or greater (> 1.0 x ULN), c.Hemoglobin grade 1 or greater (</= 10.5 g/dL), d.Platelet count grade 1 or greater (</= 99000/mm^3), e.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (> 1.0 x ULN), f.Total bilirubin grade 1 or greater (> 1.0 x ULN), g.Creatine kinase grade 1 or greater (>1.0 x ULN), h.Troponin grade 1 or greater (1.0 x UNL), or i.Any other toxicity grade 2 or above, including: proteinuria (spot urine) > 1+ and gross hematuria. For the second dose of TMC207, any other toxicity grade 3 or above, including: proteinuria (spot urine) > 1+ and gross hematuria
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 |
|---|---|---|
| RifabutinRifabutin 300 mg orally on days 20-41 | Drug | Group 1 |
| RifampinRifampin 600 mg orally on days 20-41 | Drug | Group 2 |
| TMC207TMC207 400 mg orally on days 1 and 29 | Drug | Group 1, Group 2 |
Primary outcome
Pharmacokinetic profiles determined for Rifabutin + desacetyl rifabutin
Time frame: Day 27-Day 30, Day 35 & Day 41
Pharmacokinetic profiles determined for Rifampin + desacetyl rifampin
Time frame: Day 27-Day 30, Day 35 & Day 41
Pharmacokinetic profiles for TMC207 and M2
Time frame: Day 1 - Day 15
Pharmacokinetic profiles for TMC207 and M2 in combination with steady-state rifabutin (Group 1)
Time frame: Day 29 - Day 41
Pharmacokinetic profiles for TMC207 and M2 in combination with steady-state rifampin (Group 2)
Time frame: Day 29 - Day 41
Safety of TMC207
Time frame: Over 60 days
Tolerability of TMC207
Time frame: Over 60 days
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 21 Apr 2017.
- Derived from this study: PubMed 29061739Healan AM, Griffiss JM, Proskin HM, O'Riordan MA, Gray WA, Salata RA, Blumer JL. Impact of Rifabutin or Rifampin on Bedaquiline Safety, Tolerability, and Pharmacokinetics Assessed in a Randomized Clinical Trial with Healthy Adult Volunteers. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e00855-17. doi: 10.1128/AAC.00855-17. Print 2018 Jan.
Related trials for Tuberculosis
RecruitingPhase 2
Evaluating the Safety and Immunogenicity of MTBVAC
HIV I Infection, Tuberculosis
RecruitingObservational study
Training Protocol on the Natural History of Tuberculosis
Mycobacterium Infections, Tuberculosis, Multidrug-Resistant
RecruitingObservational study
Molecular Epidemiology, Strains Genotyping of Multi-drug Resistant Tuberculosis Circulating in Central Africa Region
Multidrug-resistant Tuberculosis (MDR-TB)
Active, not recruitingPhase 2
A Study to Evaluate the Efficacy, Safety and Immunogenicity of MTBVAC in Adolescents and Adults Living in a TB Endemic Region.
Tuberculosis (TB)
Active, not recruitingObservational study
Mycobacterial and Opportunistic Infections in HIV-Negative Thai and Taiwanese Patients Associated With Autoantibodies to Interferon-gamma
Nontuberculous Mycobacteria, Mycobacterium Tuberculosis
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.
The record lists no contact. Use the official record to reach the sponsor.
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 Rifabutin, Rifampin and TMC207 in people with Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 1 inclusion and 1 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 21 Apr 2017. 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?
Pharmacokinetic profiles determined for Rifabutin + desacetyl rifabutin (time frame: Day 27-Day 30, Day 35 & Day 41). The study lists 7 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 NCT01341184, 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 21 Apr 2017.