Pulmonary Tuberculosis
Conditions
Keywords
Tuberculosis, Serial Sputum Colony Counts, Colony Forming Units, Time to Sputum Culture Positivity, PA824, pretomanid
Brief 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.
Interventions
DRUGMoxifloxacin (M)
DRUGPretomid (Pa)
DRUGPyrazinamide (Z)
DRUGRifafour
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
Sponsors
Global Alliance for TB Drug Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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. * 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.
Exclusion criteria
* 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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media | Day 57 after eight weeks of daily treatment | 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) |
| 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. | 8 weeks | Measurement of TTP in liquid culture media Mycobacteria growth indicator tube (MGIT) using standard procedures |
| Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media | 8 weeks | 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 |
| Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media | 8 weeks | 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 |
| Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media | Day 57 after eight weeks of daily treatment | 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). |
| Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm. | 8 weeks | — |
Countries
South Africa, Tanzania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks | 60 |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks | 62 |
| Drug Sensitive: Rifafour Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets | 59 |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks | 26 |
| Total | 207 |
Baseline characteristics
| Characteristic | Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | Drug Sensitive: Rifafour | Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 29.5 years STANDARD_DEVIATION 10.63 | 30.9 years STANDARD_DEVIATION 8.96 | 30.4 years STANDARD_DEVIATION 9.75 | 32.4 years STANDARD_DEVIATION 9.75 | 30.6 years STANDARD_DEVIATION 9.77 |
| HIV Status Indeterminate | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| HIV Status Missing | 0 participants | 1 participants | 0 participants | 1 participants | 2 participants |
| HIV Status Negative | 48 participants | 53 participants | 45 participants | 18 participants | 164 participants |
| HIV Status Positive | 12 participants | 8 participants | 13 participants | 7 participants | 40 participants |
| Moxifloxacin susceptibility No Result | 3 participants | 2 participants | 1 participants | 0 participants | 6 participants |
| Moxifloxacin susceptibility Resistant | 0 participants | 2 participants | 1 participants | 1 participants | 4 participants |
| Moxifloxacin susceptibility Sensitive | 56 participants | 58 participants | 57 participants | 25 participants | 196 participants |
| Moxifloxacin susceptibility Unclear | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Pyrazinamide susceptibility Missing | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Pyrazinamide susceptibility Resistant | 0 participants | 2 participants | 1 participants | 17 participants | 20 participants |
| Pyrazinamide susceptibility Sensitive | 60 participants | 59 participants | 58 participants | 9 participants | 186 participants |
| Race/Ethnicity, Customized Black | 43 participants | 46 participants | 43 participants | 15 participants | 147 participants |
| Race/Ethnicity, Customized Mixed Ethnic | 17 participants | 16 participants | 16 participants | 11 participants | 60 participants |
| Sex: Female, Male Female | 22 Participants | 22 Participants | 18 Participants | 10 Participants | 72 Participants |
| Sex: Female, Male Male | 38 Participants | 40 Participants | 41 Participants | 16 Participants | 135 Participants |
| Weight | 54.7 kilograms STANDARD_DEVIATION 8.72 | 57.6 kilograms STANDARD_DEVIATION 10.09 | 54.7 kilograms STANDARD_DEVIATION 7.95 | 57.9 kilograms STANDARD_DEVIATION 10.61 | 56 kilograms STANDARD_DEVIATION 9.25 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 52 / 60 | 57 / 62 | 50 / 59 | 23 / 26 |
| serious Total, serious adverse events | 1 / 60 | 7 / 62 | 1 / 59 | 0 / 26 |
Outcome results
Primary
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).
Time frame: 8 weeks
Population: The efficacy analysis population contained patients included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. The number of participants analyzed for this outcome was 173.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | 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. | 0.133 log10CFU/ml/day |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | 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. | 0.155 log10CFU/ml/day |
| Drug Sensitive: Rifafour | 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. | 0.112 log10CFU/ml/day |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | 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. | 0.117 log10CFU/ml/day |
Secondary
Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm.
Time frame: 8 weeks
Population: The Safety population was analyzed for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm. | 13 percentage of participants |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm. | 19 percentage of participants |
| Drug Sensitive: Rifafour | Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm. | 12 percentage of participants |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm. | 12 percentage of participants |
Secondary
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).
Time frame: Day 57 after eight weeks of daily treatment
Population: The efficacy analysis population contained participants included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. Participants included in this outcome had a valid, non-contaminated culture from the sample acquired on Day 57.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media | 65.7 percentage of patients |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media | 71.4 percentage of patients |
| Drug Sensitive: Rifafour | Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media | 37.8 percentage of patients |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media | 50.0 percentage of patients |
Secondary
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)
Time frame: Day 57 after eight weeks of daily treatment
Population: The efficacy analysis population contained participants included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. Participants included in this outcome had a valid, non-contaminated culture from the sample acquired on Day 57.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media | 82.9 percentage of participants |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media | 94.3 percentage of participants |
| Drug Sensitive: Rifafour | Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media | 87.5 percentage of participants |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media | 62.5 percentage of participants |
Secondary
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
Time frame: 8 weeks
Population: The efficacy analysis population contained patients included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. The number of participants analyzed for this outcome was 179.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | 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. | 0.020 log10hours/day |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | 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. | 0.020 log10hours/day |
| Drug Sensitive: Rifafour | 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. | 0.017 log10hours/day |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | 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. | 0.015 log10hours/day |
Secondary
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
Time frame: 8 weeks
Population: The efficacy analysis population contained participants included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. The number of participants included for this outcome was 206.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media | 42.0 days |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media | 49.0 days |
| Drug Sensitive: Rifafour | Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media | 56.0 days |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media | 56.0 days |
Secondary
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
Time frame: 8 weeks
Population: The efficacy analysis population contained patients included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. The number of participants analyzed for this outcome was 206.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg) | Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media | 28.0 days |
| Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg) | Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media | 28.0 days |
| Drug Sensitive: Rifafour | Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media | 35.0 days |
| Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg) | Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media | 35.0 days |