Pulmonary TuberculosisPhase 2NCT01215851
Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With(J-M-Pa-Z) (NC-001)
A Phase 2 study testing PA-824, Pyrazinamide and TMC207 in people with Pulmonary Tuberculosis, run by Global Alliance for TB Drug Development at 2 sites in South Africa.
Trial summary
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of TMC207 alone, TMC207 with pyrazinamide, TMC207 with PA-824, PA-824 with pyrazinamide and PA-824 with moxifloxacin and pyrazinamide, as determined by the rate of change of log CFU in sputum over the time period… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Pulmonary Tuberculosis
- What is being tested?
- PA-824, Pyrazinamide and TMC207
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 2 sitesSouth Africa
- Study dates
- Oct 2010to Aug 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide written, informed consent prior to all trial-related procedures including HIV testing.
- Male or female, aged between 18 and 65 years inclusive.
- Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
- Newly diagnosed, previously untreated, sputum smear-positive pulmonary TB.
- A chest X-ray picture which in the opinion of the Investigator is compatible with TB.
- Sputum positive on direct microscopy for acid-fast bacilli (at least 1+ on the IUATLD/WHO scale).
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- Ability to produce an adequate volume of sputum as estimated from a spot assessment (estimated 10 ml or more overnight production).
- Females may participate if they are: 1) of non-childbearing potential (have had a bilateral oophorectomy and/or hysterectomy or have been postmenopausal for at least 12 consecutive months), 2) if they are using effective birth control methods and are willing to continue practicing birth control methods throughout treatment or 3) be non-heterosexually active, practice sexual abstinence or have a vasectomized partner (confirmed sterile). Therefore to be eligible for this study women of childbearing potential should either: 1) use a double barrier method to prevent pregnancy (i.e. use a condom with either diaphragm or cervical cap) or 2) use hormonal based contraceptives in combination with a barrier contraceptive, or 3) use an intrauterine device in combination with a barrier contraceptive. They must also be willing to continue these contraceptive measures until 6 months after the last dose of study medication or 6 months after discontinuation from study medication in case of premature discontinuation. (Note: Hormone-based contraception alone may not be reliable when taking IMP; therefore, hormone-based contraceptives alone cannot be used by female participants to prevent pregnancy).
- Male participants who are having heterosexual intercourse with females of child-bearing potential are required to use one of the following birth control methods during their participation in the trial and for 12 weeks after their last dose of study medication to prevent pregnancy:
- a double barrier method which can include a male condom, diaphragm, cervical cap, or female condom; or
- a barrier method combined with hormone-based contraceptives or an intra-uterine device for the female partner.
- The use of the above mentioned birth control method does not apply if the male participant has been vasectomised or has had a bilateral orchidectomy minimally one month prior to screening, or is not heterosexually active, or practice sexual abstinence or if the female sexual partner has had a bilateral oophorectomy and/or hysterectomy or has been postmenopausal for at least 12 consecutive months.
Who cannot join
- Medical History
- Evidence of clinically significant (as judged by the investigator), metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
- Poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator.
- A history of previous TB.
- Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.
- History of allergy to the IMP or related substances, including a known allergy to any fluoroquinolone antibiotic, history of tendinopathy associated with quinolones or suspected hypersensitivity to any rifamycin antibiotics.
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- Isoniazid-resistant and Rifampicin-resistant bacteria detected with a sputum specimen collected within the pre-treatment period and tested at the study laboratory.
- Known or suspected, current or history of within the past 2 years, alcohol or drug abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the participant.
- HIV infected participants:
- having a CD4+ count <300 cells/µL;
- or having received antiretroviral therapy medication within the last 90 days;
- or having received oral or intravenous antifungal medication within the last 90 days;
- or with an AIDS-defining opportunistic infection or malignancies (except pulmonary TB).
- Having participated in other clinical studies with investigational agents within 8 weeks prior to trial start.
- Significant cardiac arrhythmia requiring medication.
- Participants with the following at screening:
- Marked prolongation of QT/QTc interval, e.g., confirmed demonstration of QTcF (Fridericia correction) or QTcB (Bazett correction) interval >450 ms at screening;
- History of additional risk factors for Torsade de Pointes, e.g., heart failure, hypokalemia, family history of Long QT Syndrome;
- Use of concomitant medications that prolong the QT/QTc interval (see exclusion criterion 22 as well as list of disallowed medication in Section 4.7.2);
- Pathological Q waves (defined as >40ms or depth >0.4-0.5mV);
- ECG evidence of ventricular pre-excitation;
- ECG evidence of complete or incomplete left bundle branch block or right bundle branch block;
- ECG evidence of second or third degree heart block;
- Intraventricular conduction delay with QRS duration >120ms;
- Bradycardia as defined by sinus rate <50bpm.
- Females who are pregnant, breast-feeding, or planning to conceive a child within 6 months of cessation of treatment.
- Males planning to conceive a child within twelve weeks of cessation of treatment.
- History and/or presence (or evidence) of neuropathy or epilepsy.
- Diabetes Mellitus requiring insulin.
- History of lens opacity or evidence of lens opacity on slit lamp ophthalmologic examination.
- For males, any evidence or history of a clinically significant abnormality in the reproductive system, including but not limited to the following: serum testosterone, luteinizing hormone (LH), and/or follicle-stimulating hormone (FSH) levels outside the laboratory reference range. An evaluation resulting in an isolated abnormal value (i.e., only 1 of the 3 hormones is abnormal) may be repeated using a morning (ideally, 8am) serum specimen. If the laboratory value on the repeat specimen is outside the laboratory reference range, unless the result is deemed not clinically significant by the Investigator in consultation with the Sponsor Medical Monitor, the participant should be excluded.
- Specific Treatments
- Previously received treatment with TMC207 or PA-824 as part of a clinical trial.
- Treatment received with any drug active against MTB within the 3 months prior to Visit 1 (e.g. isoniazid, ethambutol, amikacin, cycloserine, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, fluoroquinolones, thioamides, metronidazole).
- Any diseases or conditions in which the use of the standard TB drugs or any of their components is contra-indicated, including but not limited to allergy to any TB drug, their component or to the IMP.
- Any disease or conditions in which any of the medicinal products listed in the section pertaining to prohibited medications is used.
- Concomitant use of any drug known to prolong QTc interval (including amiodarone, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, procainamide, quinidine, sotalol, sparfloxacin, thioridazine). The exception is moxifloxacin which is one of the drugs being evaluated in this study, with extensive ECG monitoring to help ensure patient safety.
- Use of any drugs or substances within 30 days prior to dosing known to be strong inhibitors or inducers of cytochrome P450 enzymes (such as quinidine, tyramine, ketoconazole, testosterone, quinine, gestodene, metyrapone, phenelzine, doxorubicin, troleandomycin, cyclobenzaprine, erythromycin, cocaine, furafylline, cimetidine, dextromethorphan). Exceptions may be made for participants that have received 3 days or less of one of these drugs or substances, if there has been a wash-out period before administration of IMP equivalent to at least 5 half-lives of that drug or substance.
- Use of any therapeutic agents known to alter any major organ function (e.g., barbiturates, opiates, phenothiazines, cimetidine) within 30 days prior to dosing.
- Use of systemic glucocorticoids within one year prior to dosing.
- Based on Laboratory Abnormalities
- Participants with the following toxicities at screening as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (November 2007):
- creatinine grade 2 or greater (>1.5 times upper limit of normal [ULN]);
- lipase grade 3 or greater (>2.0 x ULN);
- hemoglobin grade 4 (<6.5 g/dL);
- platelets grade 2 or greater (under 50x109 cells/L);
- serum potassium grade 2 or greater (<3.5 mEq/L);
- aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN) to be excluded;
- alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN) to be excluded;
- alkaline phosphatase (ALP) grade 4 (>8.0 x ULN) to be excluded, grade 3 (≥3.0 x ULN) must be discussed with the sponsor Medical Monitor;
- total bilirubin grade 3 or greater (>2.0 x ULN, or >1.50 x ULN when accompanied by any increase in other liver function test) to be excluded, grade 2 (>1.50 x ULN, or >1.25 x ULN when accompanied by any increase in other liver function test) must be discussed with the sponsor Medical Monitor.
Trial locations and contacts
2 sites in 1 country.
South Africa2 sites
Centre for Tuberculosis Research Innovation, UCT Lung Institute
Cape Town, 7700
Task Applied Science, Karl Bremer Hospital
Cape Town
About this study
Official title: A Phase II Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of the Following: TMC207 Alone, TMC207 Plus Pyrazinamide,TMC207 Plus PA-824,PA-824 Plus Pyrazinamide and PA-824 Plus Pyrazinamide and Moxifloxacin, in Adult Patients With Newly Diagnosed, Smear-Positive Pulmonary Tuberculosis.
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of TMC207 alone, TMC207 with pyrazinamide, TMC207 with PA-824, PA-824 with pyrazinamide and PA-824 with moxifloxacin and pyrazinamide, as determined by the rate of change of log CFU in sputum over the time period Day 0-14 in participants with smear positive pulmonary tuberculosis (TB). A control group will receive standard treatment.
- Conditions
- Pulmonary Tuberculosis
- Being tested
- PA-824, Pyrazinamide, TMC207, Rifafour, Moxifloxacin
- Keywords
- Tuberculosis, EBA, TMC207, pretomanid, Early Bactericidal Activity, Pulmonary Tuberculosis, PA-824, bedaquiline, pyrazinamide, moxifloxacin, ethambutol, rifafour
- Medical subject headings
- Tuberculosis, Pulmonary, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PA-824Drug
200 mg tablet, once daily for 14 days
PyrazinamideDrug
Dosed by Weight
TMC207Drug
TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14
RifafourDrug
Rifafour e-275
MoxifloxacinDrug
moxifloxacin 400 mg
| Study group | Role | What they receive |
|---|---|---|
| TMC207 | Experimental | TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo administered once daily Receives: Drug: TMC207 |
| TMC207 and pyrazinamide | Experimental | TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: < or = 55kg received 2 tablets/day; >55kg to 75kg received 3 tablets/day; >75kg received 4 tablets/day Receives: Drug: Pyrazinamide; Drug: TMC207 |
| PA-824 and pyrazinamide | Experimental | PA-824 administered once daily as 200mg tablets and pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: < or = 55kg received 2 tablets/day; >55kg to 75kg received 3 tablets/day; >75kg received 4 tablets/day and moxifloxacin placebo (matched to moxifloxacin tablets) administered once daily Receives: Drug: PA-824; Drug: Pyrazinamide |
| PA-824 and moxifloxacin and pyrazinamide | Experimental | PA-824 administered once daily as 200mg tablets and pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: < or = 55kg received 2 tablets/day; >55kg to 75kg received 3 tablets/day; >75kg received 4 tablets/day and moxifloxacin administered once daily as 400mg tablets Receives: Drug: PA-824; Drug: Moxifloxacin |
| Rifafour e-275 mg | Active comparator | Rifafour e-275 administered once daily with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dose by weight as follows: 30kg-37kg received 2 tablets/day; 38kg-54kg received 3 tablets/days; 55kg-70kg received 4 tablets/day; > or = 71kg received 5 tablets/day Receives: Drug: Rifafour |
| TMC207 and PA-824 | Experimental | TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus PA-824 administered once daily as 200mg tablets Receives: Drug: PA-824; Drug: TMC207 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
Measured: 14 consecutive days of treatment
Secondary outcomes (4)
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
Measured: Day 0-2
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
Measured: Day 2-14
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 7-14).
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
Measured: Day 7-14
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)
The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (TTP versus Day).
Measured: 14 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionMay 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andreas Diacon, Principal investigator, Karl Bremer Hospital, Cape Town South africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01215851
- Sponsor's protocol ID
- NC-001-(J-M-Pa-Z)
- Status last verified
- Jan 2017
- First submitted
- 5 Oct 2010
- Last updated
- 28 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, van Niekerk C, Everitt D, Winter H, Becker P, Mendel CM, Spigelman MK. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet. 2012 Sep 15;380(9846):986-93. doi: 10.1016/S0140-6736(12)61080-0. Epub 2012 Jul 23.
PubMed 22828481
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of the Following: TMC207 Alone, TMC207 Plus Pyrazinamide,TMC207 Plus PA-824,PA-824 Plus Pyrazinamide and PA-824 Plus Pyrazinamide and Moxifloxacin, in Adult Patients With Newly Diagnosed, Smear-Positive Pulmonary Tuberculosis.
- ClinicalTrials.gov ID
- NCT01215851
- Acronym / sponsor ID
- NC-001-(J-M-Pa-Z)
- Conditions
- Pulmonary Tuberculosis
- Keywords
- Tuberculosis, EBA, TMC207, pretomanid, Early Bactericidal Activity, Pulmonary Tuberculosis, PA-824, bedaquiline
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Global Alliance for TB Drug DevelopmentUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- May 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 7 Oct 2010 (estimated)
- Results
- Posted 1 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of TMC207 alone, TMC207 with pyrazinamide, TMC207 with PA-824, PA-824 with pyrazinamide and PA-824 with moxifloxacin and pyrazinamide, as determined by the rate of change of log CFU in sputum over the time period Day 0-14 in participants with smear positive pulmonary tuberculosis (TB). A control group will receive standard treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| TMC207 | Experimental | Drug: TMC207TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo administered once daily |
| TMC207 and pyrazinamide | Experimental | Drug: Pyrazinamide, Drug: TMC207TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: < or = 55kg received 2 tablets/day; >55kg to 75kg received 3 tablets/day; >75kg received 4 tablets/day |
| PA-824 and pyrazinamide | Experimental | Drug: PA-824, Drug: PyrazinamidePA-824 administered once daily as 200mg tablets and pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: < or = 55kg received 2 tablets/day; >55kg to 75kg received 3 tablets/day; >75kg received 4 tablets/day and moxifloxacin placebo (matched to moxifloxacin tablets) administered once daily |
| PA-824 and moxifloxacin and pyrazinamide | Experimental | Drug: PA-824, Drug: MoxifloxacinPA-824 administered once daily as 200mg tablets and pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: < or = 55kg received 2 tablets/day; >55kg to 75kg received 3 tablets/day; >75kg received 4 tablets/day and moxifloxacin administered once daily as 400mg tablets |
| Rifafour e-275 mg | Active comparator | Drug: RifafourRifafour e-275 administered once daily with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dose by weight as follows: 30kg-37kg received 2 tablets/day; 38kg-54kg received 3 tablets/days; 55kg-70kg received 4 tablets/day; > or = 71kg received 5 tablets/day |
| TMC207 and PA-824 | Experimental | Drug: PA-824, Drug: TMC207TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus PA-824 administered once daily as 200mg tablets |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Provide written, informed consent prior to all trial-related procedures including HIV testing.
- Male or female, aged between 18 and 65 years inclusive.
- Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
- Newly diagnosed, previously untreated, sputum smear-positive pulmonary TB.
- A chest X-ray picture which in the opinion of the Investigator is compatible with TB.
Key exclusion criteria (51 listed)
- Medical History
- Evidence of clinically significant (as judged by the investigator), metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
- Poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator.
- A history of previous TB.
- Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.
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 |
|---|---|---|
| PA-824200 mg tablet, once daily for 14 days | Drug | PA-824 and moxifloxacin and pyrazinamide, PA-824 and pyrazinamide, TMC207 and PA-824 |
| PyrazinamideDosed by Weight | Drug | PA-824 and pyrazinamide, TMC207 and pyrazinamide |
| TMC207TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 | Drug | TMC207, TMC207 and PA-824, TMC207 and pyrazinamide |
| RifafourRifafour e-275 | Drug | Rifafour e-275 mg |
| Moxifloxacinmoxifloxacin 400 mg | Drug | PA-824 and moxifloxacin and pyrazinamide |
Primary outcome
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).
Time frame: 14 consecutive days of treatment
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
4 secondary outcomes
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).
Time frame: Day 0-2
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).
Time frame: Day 2-14
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 7-14).
Time frame: Day 7-14
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)
Time frame: 14 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22828481Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, van Niekerk C, Everitt D, Winter H, Becker P, Mendel CM, Spigelman MK. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet. 2012 Sep 15;380(9846):986-93. doi: 10.1016/S0140-6736(12)61080-0. Epub 2012 Jul 23.
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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.
Andreas Diacon principal investigator
Karl Bremer Hospital, Cape Town South africa
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PA-824, Pyrazinamide and TMC207 in people with Pulmonary Tuberculosis, run by Global Alliance for TB Drug Development at 2 sites in South Africa.
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 12 inclusion and 51 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 28 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14). (time frame: 14 consecutive days of treatment). 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 NCT01215851, 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 28 Feb 2017.