Pulmonary TuberculosisPhase 2NCT01498419
Evaluation of 8 Weeks of Treatment With the Combination of Moxifloxacin, PA-824 and Pyrazinamide in Patients With Drug Sensitive and Multi Drug-Resistant Pulmonary Tuberculosis (TB) (NC-002)
A Phase 2 study testing Moxifloxacin (M), Pretomid (Pa) and Pyrazinamide (Z) in people with Pulmonary Tuberculosis, run by Global Alliance for TB Drug Development at 8 sites in 2 countries.
Trial summary
The purpose of this study is to assess the mycobactericidal activity of the moxifloxacin plus PA-824 plus pyrazinamide regimen after 8 weeks of treatment. 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?
- Moxifloxacin (M), Pretomid (Pa) and Pyrazinamide (Z)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 207 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Mar 2012to Jul 2013
- 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 (if an HIV test was performed within 1 month prior to trial start, it should not be repeated as long as documentation can be provided [ELISA and/or Western Blot]).
- Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
- Sputum smear-positive pulmonary TB (at trial appointed laboratory). For Drug Sensitive TB treatment arms, subjects should be newly diagnosed and previously untreated. Exception: Participants can be included in the trial if they were diagnosed and treated for TB greater than 5 years prior to screening and can provide documentation of cure for that episode. Additionally, participants who have previously received H prophylactically can be included as long as that treatment is/was discontinued at least 7 days prior to randomization into this trial. Drug sensitive status to be confirmed with fluoroquinolone, rifampicin and isoniazid susceptibility testing at screening using Hain Plus rapid sputum test.
- For the MDR-TB treatment arm only: Subjects with smear-positive MDR infection, defined as confirmed resistance to at least both R and H confirmed at screening for entry into this trial. Resistance to R and H will be determined using the rapid screen test (Hain Plus). If the first spot sputum shows an indeterminate result, the test must be repeated on freshly collected spot sputum or overnight sputum and that result may be used.
- Subjects with newly diagnosed MDR-TB are defined as a) subjects with MDR-TB who have never been treated for TB before, or b) subjects with MDR-TB who have previously been treated with only one course of first-line TB drugs (H, R, E, Z and/or S) and that treatment is/was discontinued at least 7 days prior to randomization into this trial. Additionally, MDR-TB participants who have previously received H prophylactically can be included as long as that treatment is/was discontinued at least 7 days prior to randomization into this trial.
- A chest X-ray picture which in the opinion of the Investigator is compatible with TB.
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- Sputum positive (at site laboratory) on direct microscopy for acid-fast bacilli (at least 1+ on the IUATLD/WHO scale).
- 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, tubal ligation 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 one week after the last dose of study medication or one week 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 three months prior to screening, or is not heterosexually active, or practices sexual abstinence or if the female sexual partner has had a bilateral oophorectomy, tubal ligation and/or hysterectomy or has been postmenopausal for at least 12 consecutive months.
Who cannot join
- 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) including myasthenia gravis and malaria.
- End stage liver failure (class Child Pugh C).
- Poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator.
- Clinically significant evidence of extrathoracic TB (e.g. miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.
- History of allergy or hypersensitivity to any of the study 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.
- Resistance to fluoroquinolones (Hain plus rapid test) and/or pyrazinamide. Participants may be included in the study prior to receipt of the susceptibility test results for fluoroquinolones or pyrazinamide, however once these are received after a participant has entered into the study and if the results show the participant is resistant to fluoroquinolones and/or pyrazinamide, such a participant should be removed from the trial. DS participants will not be replaced, but MDR-TB participants taking part in the EBA Sub-Study could be replaced after consultation and written approval with the sponsor.
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- Known (positive urine drug screen) 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.
- For HIV infected participants:
- having a CD4+ count <200 cells/µL;
- or having received 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 study/ies with investigational agent/s within 8 weeks prior to trial start.
- Significant cardiac arrhythmia requiring medication.
- Participants with the following at screening (per measurements and reading done by Central ECG):
- 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 are known to prolong the QT/QTc interval (see exclusion criterion 21 as well as list of disallowed medication in the study protocol);
- Any clinically significant, in the opinion of the Investigator, ECG abnormality.
- Females who are pregnant, breast-feeding, or planning to conceive a child within one week 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.
- Previously received treatment with PA-824 as part of a clinical trial.
- For the DS-TB treatment arms: treatment with any drug active against MTB within the 3 months prior to Visit 1 (e.g. isoniazid, ethambutol, amikacin, clofazimine, cycloserine, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, fluoroquinolones, thioamides, metronidazole). Exceptions noted in Inclusion Criteria.
- For the MDR-TB Subjects: previously treated for MDR-TB. Defined as having received multiple courses of first-line therapy or any second-line TB drug, including any of the following anti-mycobacterials: any aminoglycoside except streptomycin, any fluoroquinolone, the thioamides, prothionamide or ethionamide and cycloserine.
- 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 of the protocol pertaining to prohibited medications is used.
- Use of any drug within 30 days prior to dosing 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). 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. The Investigator may choose at his/her discretion to make an exception for opiates or painkillers if they were part of prescribed medication for cough or underlying disease.
- Use of systemic glucocorticoids within one year prior to dosing.
- 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]);
- creatinine clearance (CrCl) level less than 30 mls/min. according to the Cockcroft-Gault Formula;
- hemoglobin grade 4 (<6.5 g/dL);
- platelets grade 2 or greater (under 50x109 cells/L);
- serum potassium less than the lower limit of normal for the laboratory;
- aspartate aminotransferase (AST) grade 3 or greater (≥3.0 x ULN) to be excluded;
- alanine aminotransferase (ALT) grade 3 or greater (≥3.0 x ULN) to be excluded;
- alkaline phosphatase (ALP) grade 4 (>8.0 x ULN) to be excluded, grade 3 (≥3.0 - 8.0 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
8 sites in 2 countries.
8 sites in 2 countries
South Africa6 sites
Task Applied Science, Karl Bremer Hospital
Cape Town, 7531
University of Cape Town Lung Institute (Pty) Ltd
Cape Town, 7700
KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH)
Durban, 4013
CHRU Themba Lethu Clinic
Johannesburg
Klerksdorp Tshepong Hospital
Klerksdorp, 2570
The Aurum Institute: Tembisa Hospital
Tembisa, 1736
Tanzania2 sites
Ifakara Health Institute
Bagamoyo
Mbeya Medical Research Programme
Mbeya
About this study
Official title: A Phase II Open-Label Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of the Combination of Moxifloxacin Plus PA-824 Plus Pyrazinamide After 8 Weeks of Treatment in Adult Patients With Newly Diagnosed Drug-Sensitive or Multi Drug-Resistant, Smear-Positive Pulmonary Tuberculosis
The purpose of this study is to assess the mycobactericidal activity of the moxifloxacin plus PA-824 plus pyrazinamide regimen after 8 weeks of treatment.
- Conditions
- Pulmonary Tuberculosis
- Being tested
- Moxifloxacin (M), Pretomid (Pa), Pyrazinamide (Z), Rifafour
- Keywords
- Tuberculosis, Serial Sputum Colony Counts, Colony Forming Units, Time to Sputum Culture Positivity, PA824, pretomanid
- 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.
Moxifloxacin (M)Drug
Pretomid (Pa)Drug
Also called PA-824
Pyrazinamide (Z)Drug
RifafourDrug
Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: 2 tablets, 38-54 kg: 3 tablets, 55-70 kg: 4 tablets: 71 kg and over: 5 tablets
| Study group | Role | What they receive |
|---|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | Experimental | Drug Sensitive Participants: One moxifloxacin (M) 400 mg tablet plus one Pretomanid (PA-824) 100 mg tablet plus three pyrazinamide 500 mg tablets taken once daily for 8 weeks Receives: Drug: Moxifloxacin (M); Drug: Pretomid (Pa); Drug: Pyrazinamide (Z) |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | Experimental | Drug Sensitive Participants: One moxifloxacin (M) 400 mg tablet plus one Pretomanid (PA-824) 200 mg tablet plus three pyrazinamide 500 mg tablets taken once daily for 8 weeks Receives: Drug: Moxifloxacin (M); Drug: Pretomid (Pa); Drug: Pyrazinamide (Z) |
| Drug Sensitive: Rifafour | Active comparator | Drug Sensitive Participants: Rifafour was administered orally once daily for 8 weeks according to weight: 30 kg to 37 kg: two tablets; 38 kg to 54 kg: three tablets; 55 kg to 70 kg: four tablets; ≥71 kg: five tablets Receives: Drug: Rifafour |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | Experimental | Multi Drug-Resistant Participants: One moxifloxacin (M) 400 mg tablet plus one Pretomanid (PA-824) 200 mg tablet plus three pyrazinamide 500 mg tablets taken once daily for 8 weeks Receives: Drug: Moxifloxacin (M); Drug: Pretomid (Pa); Drug: Pyrazinamide (Z) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Rate of Change in Colony Forming Units (CFUs) Using Non-linear Mixed Effects Modeling of the Serial Sputum Colony Counts (SSCC) Over 8 Weeks of Treatment.
The primary efficacy endpoint was bactericidal activity characterized by the daily rate of change in mean log10CFU counts during 8 weeks of treatment (bactericidal activity assessed by CFU on solid media for days 0-56).
Measured: 8 weeks
Secondary outcomes (6)
Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media
liquid culture = Mycobacteria growth indicator tube (MGIT) Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB
Measured: 8 weeks
Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media
Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB. (Day 57)
Measured: Day 57 after eight weeks of daily treatment
The Rate of Change in Time to Sputum Culture Positivity (TTP) Through 8 Weeks in the MGIT System in Sputum Over 8 Weeks in Participants as Derived From a Non-linear Regression Model.
Measurement of TTP in liquid culture media Mycobacteria growth indicator tube (MGIT) using standard procedures
Measured: 8 weeks
Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm.
Measured: 8 weeks
Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media
Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB
Measured: 8 weeks
Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media
Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB. This was measured at visit 24(Day 57).
Measured: Day 57 after eight weeks of daily treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2011 (estimated)
- Study startMar 2012
- Primary completionApr 2013
- Study completionJul 2013
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
- None (open label)
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rodney Dawson, MD, Principal investigator, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01498419
- Sponsor's protocol ID
- NC-002-(M-Pa-Z)
- Status last verified
- Jan 2017
- First submitted
- 21 Dec 2011
- Last updated
- 28 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Dawson R, Diacon AH, Everitt D, van Niekerk C, Donald PR, Burger DA, Schall R, Spigelman M, Conradie A, Eisenach K, Venter A, Ive P, Page-Shipp L, Variava E, Reither K, Ntinginya NE, Pym A, von Groote-Bidlingmaier F, Mendel CM. Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drug-susceptible or drug-resistant pulmonary tuberculosis. Lancet. 2015 May 2;385(9979):1738-1747. doi: 10.1016/S0140-6736(14)62002-X. Epub 2015 Mar 18.
PubMed 25795076
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-Label Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of the Combination of Moxifloxacin Plus PA-824 Plus Pyrazinamide After 8 Weeks of Treatment in Adult Patients With Newly Diagnosed Drug-Sensitive or Multi Drug-Resistant, Smear-Positive Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT01498419
- Acronym / sponsor ID
- NC-002-(M-Pa-Z)
- Conditions
- Pulmonary Tuberculosis
- Keywords
- Tuberculosis, Serial Sputum Colony Counts, Colony Forming Units, Time to Sputum Culture Positivity, PA824, pretomanid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- Global Alliance for TB Drug DevelopmentUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Apr 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 23 Dec 2011 (estimated)
- Results
- Posted 12 Dec 2016
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 mycobactericidal activity of the moxifloxacin plus PA-824 plus pyrazinamide regimen after 8 weeks of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | Experimental | Drug: Moxifloxacin (M), Drug: Pretomid (Pa), Drug: Pyrazinamide (Z)Drug Sensitive Participants: One moxifloxacin (M) 400 mg tablet plus one Pretomanid (PA-824) 100 mg tablet plus three pyrazinamide 500 mg tablets taken once daily for 8 weeks |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | Experimental | Drug: Moxifloxacin (M), Drug: Pretomid (Pa), Drug: Pyrazinamide (Z)Drug Sensitive Participants: One moxifloxacin (M) 400 mg tablet plus one Pretomanid (PA-824) 200 mg tablet plus three pyrazinamide 500 mg tablets taken once daily for 8 weeks |
| Drug Sensitive: Rifafour | Active comparator | Drug: RifafourDrug Sensitive Participants: Rifafour was administered orally once daily for 8 weeks according to weight: 30 kg to 37 kg: two tablets; 38 kg to 54 kg: three tablets; 55 kg to 70 kg: four tablets; ≥71 kg: five tablets |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | Experimental | Drug: Moxifloxacin (M), Drug: Pretomid (Pa), Drug: Pyrazinamide (Z)Multi Drug-Resistant Participants: One moxifloxacin (M) 400 mg tablet plus one Pretomanid (PA-824) 200 mg tablet plus three pyrazinamide 500 mg tablets taken once daily for 8 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Provide written, informed consent prior to all trial-related procedures including HIV testing (if an HIV test was performed within 1 month prior to trial start, it should not be repeated as long as documentation can be provided [ELISA and/or Western Blot]).
- Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
- Sputum smear-positive pulmonary TB (at trial appointed laboratory). For Drug Sensitive TB treatment arms, subjects should be newly diagnosed and previously untreated. Exception: Participants can be included in the trial if they were diagnosed and treated for TB greater than 5 years prior to screening and can provide documentation of cure for that episode. Additionally, participants who have previously received H prophylactically can be included as long as that treatment is/was discontinued at least 7 days prior to randomization into this trial. Drug sensitive status to be confirmed with fluoroquinolone, rifampicin and isoniazid susceptibility testing at screening using Hain Plus rapid sputum test.
- For the MDR-TB treatment arm only: Subjects with smear-positive MDR infection, defined as confirmed resistance to at least both R and H confirmed at screening for entry into this trial. Resistance to R and H will be determined using the rapid screen test (Hain Plus). If the first spot sputum shows an indeterminate result, the test must be repeated on freshly collected spot sputum or overnight sputum and that result may be used.
- Subjects with newly diagnosed MDR-TB are defined as a) subjects with MDR-TB who have never been treated for TB before, or b) subjects with MDR-TB who have previously been treated with only one course of first-line TB drugs (H, R, E, Z and/or S) and that treatment is/was discontinued at least 7 days prior to randomization into this trial. Additionally, MDR-TB participants who have previously received H prophylactically can be included as long as that treatment is/was discontinued at least 7 days prior to randomization into this trial.
Key exclusion criteria (41 listed)
- 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) including myasthenia gravis and malaria.
- End stage liver failure (class Child Pugh C).
- Poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator.
- Clinically significant evidence of extrathoracic TB (e.g. miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.
- History of allergy or hypersensitivity to any of the study 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.
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 |
|---|---|---|
| Moxifloxacin (M) | Drug | Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg), Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg), Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) |
| Pretomid (Pa)Also: PA-824 | Drug | Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg), Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg), Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) |
| Pyrazinamide (Z) | Drug | Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg), Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg), Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) |
| RifafourRifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: 2 tablets, 38-54 kg: 3 tablets, 55-70 kg: 4 tablets: 71 kg and over: 5 tablets | Drug | Drug Sensitive: Rifafour |
Primary outcome
The Rate of Change in Colony Forming Units (CFUs) Using Non-linear Mixed Effects Modeling of the Serial Sputum Colony Counts (SSCC) Over 8 Weeks of Treatment.
Time frame: 8 weeks
The primary efficacy endpoint was bactericidal activity characterized by the daily rate of change in mean log10CFU counts during 8 weeks of treatment (bactericidal activity assessed by CFU on solid media for days 0-56).
6 secondary outcomes
Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media
Time frame: 8 weeks
Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media
Time frame: Day 57 after eight weeks of daily treatment
The Rate of Change in Time to Sputum Culture Positivity (TTP) Through 8 Weeks in the MGIT System in Sputum Over 8 Weeks in Participants as Derived From a Non-linear Regression Model.
Time frame: 8 weeks
Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm.
Time frame: 8 weeks
Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media
Time frame: 8 weeks
Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media
Time frame: Day 57 after eight weeks of daily treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25795076Dawson R, Diacon AH, Everitt D, van Niekerk C, Donald PR, Burger DA, Schall R, Spigelman M, Conradie A, Eisenach K, Venter A, Ive P, Page-Shipp L, Variava E, Reither K, Ntinginya NE, Pym A, von Groote-Bidlingmaier F, Mendel CM. Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drug-susceptible or drug-resistant pulmonary tuberculosis. Lancet. 2015 May 2;385(9979):1738-1747. doi: 10.1016/S0140-6736(14)62002-X. Epub 2015 Mar 18.
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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.
Rodney Dawson, MD principal investigator
University of Cape Town
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Moxifloxacin (M), Pretomid (Pa) and Pyrazinamide (Z) in people with Pulmonary Tuberculosis, run by Global Alliance for TB Drug Development at 8 sites in 2 countries.
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 13 inclusion and 41 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 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in South Africa, Tanzania. 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 12 Dec 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?
The Rate of Change in Colony Forming Units (CFUs) Using Non-linear Mixed Effects Modeling of the Serial Sputum Colony Counts (SSCC) Over 8 Weeks of Treatment. (time frame: 8 weeks). 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 NCT01498419, 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 Jun 2018.