Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis, MDR, Tuberculosis, Extensively Drug-Resistant Tuberculosis, Pre-XDR-TB, XDR-TB
Conditions
Keywords
Tuberculosis, Multi Drug-Resistant Tuberculosis, Extensively Drug-Resistant Tuberculosis, Drug-Resistant Tuberculosis, Pretomanid, PA-824, Bedaquiline, Linezolid, NC-007, TB Alliance, pre-XDR-TB, Sirturo, Zyvox, ZeNix
Brief summary
To evaluate the efficacy, safety and tolerability of various doses and durations of linezolid plus bedaquiline and pretomanid after 26 weeks of treatment in participants with either pulmonary XDR-TB, pre-XDR-TB, or treatment intolerant or non-responsive MDR-TB.
Detailed description
A phase 3, multi-center, partially-blinded, randomized clinical trial in 4 parallel treatment groups. Bedaquiline and pretomanid treatment will not be blinded. Linezolid treatment dose and duration will be double-blinded. Participants will have a screening period of up to 14 days and will be randomized to receive one of the 4 active treatment arms. Participants will be randomized to one of the 4 regimens in a 1:1:1:1 ratio, using an interactive voice and web response system (IXRS) which will utilize a randomization system using stratification with a random element to allocate participants evenly across the arms by HIV status and type of TB. Each participant will receive 26 weeks of treatment. If participant's week 16 sputum sample is culture positive between the week 16 and week 26 treatment visits and their clinical condition suggests they may have an ongoing TB infection, Investigator may consider extending current treatment to 39 weeks. If the culture results between week 16 and week 26 are contaminated, missing or considered an isolated positive without clinical significance, available culture results should be used to make this decision. All decisions regarding treatment extension should be discussed with and approved by, in consultation with the Sponsor Medical Monitor before implementation. The treatment may also require modification due to toxicities. All dose modifications should be discussed with the Sponsor Medical Monitor prior to implementation, unless a pause or dose reduction is required urgently for safety concerns. Participants will be followed for 78 weeks after end of treatment.
Interventions
DRUGPretomanid
200mg tablets
DRUGLinezolid
Scored 600mg tablets
DRUGBedaquiline
100mg tablets
Scored 600 mg tablets
Sponsors
Global Alliance for TB Drug Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Participants, trial investigators and staff, including laboratory staff, will be blinded to dose and scheduled duration of linezolid. Bedaquiline and pretomanid dosing will not be blinded. There will be three unblinded analyses which will contain results by linezolid treatment group in aggregate. The first analysis will be after all participants have completed 26 weeks of treatment and here sites, participants, and Sponsor staff will not be unblinded to individual linezolid treatment information. A limited number of statisticians will have access to individual linezolid treatment assignments. The blind for all individual participants will be broken for the primary endpoint analysis (the second unblinded analysis) once all clinical data and outcome parameters have been captured, no more data queries are pending, and the statistical analysis plan has been finalized. The third analysis will occur when all participants have completed 78 weeks of follow-up after end of treatment.
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, aged 14 years or older. * One of the following with documentation of culture positive or molecular test within 3 months of screening: * XDR-TB defined as resistance to rifamycins, a fluoroquinolone AND an injectable OR * Pre-XDR-TB with defined as resistance to rifamycins, and to a fluoroquinolone OR an injectable OR * MDR-TB with resistance to rifamycins, and either non-responsive or non-tolerant to current treatment. * Of non-childbearing potential or willing to practice effective birth control methods. * Complete informed consent form.
Exclusion criteria
* Karnofsky score \< 60 at screening. * Body mass index (BMI) \< 17 kg/m2 * Participants who are expected to require a surgical procedure (for Pulmonary TB). * Any risk factor for QT prolongation * Pregnant or breast-feeding * Any planned contraindicated medicines or received more than 2 weeks of bedaquiline, linezolid or delamanid prior to first dose of IMP. * A peripheral neuropathy of Grade 3 or 4, according to DMID. Or, participants with a Grade 1 or 2 neuropathy which is likely to progress/worsen over the course of the study, in the opinion of the Investigator * Any of the following lab toxicities/abnormalities: * Viral load \>1000 copies/mL (Unless newly diagnosed HIV and not yet on ART who otherwise qualify for participation); * CD4+ count \< 100 cells/µL (HIV positive participants); * Serum potassium less than the lower limit of normal for the laboratory; * Hemoglobin \< 9.0 g/dL or 90g/L; * Platelets \<100,000/mm3 or \< 100 x 10\^9/L * Absolute neutrophil count (ANC) \< 1500/ mm3 or \< 1.5 x 10\^9/L * Aspartate aminotransferase (AST) and Alanini aminotransferase (ALT) Grade 3 or greater (\> 3.0 x ULN) * Total bilirubin greater than 1.5 x ULN * Direct bilirubin greater than ULN * Serum creatinine level greater than 1.5 times upper limit of normal * Albumin \<3.0 g/dl or \< 30 g/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | 26 weeks | Unfavourable status: 1. Participants not classified as having achieved or maintained culture negative status when last seen 2. Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture 3. Participants who had a positive culture not followed by at least two negative cultures when last seen 4. Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide 5. Participants definitely or possibly dying from TB related cause during the follow-up phase 6. Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy 7. Participants who have had surgery and the resected tissue is cultured and is positive for MTB 8. Participants lost to follow up or withdrawn from the study before the end of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | 78 weeks | Unfavourable status: 1. Participants not classified as having achieved or maintained culture negative status when last seen 2. Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture 3. Participants who had a positive culture not followed by at least two negative cultures when last seen 4. Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide 5. Participants definitely or possibly dying from TB related cause during the follow-up phase 6. Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy 7. Participants who have had surgery and the resected tissue is cultured and is positive for MTB 8. Participants lost to follow up or withdrawn from the study before the end of treatment |
| Time to Sputum Culture Conversion to Negative Status Through the Treatment Period | 26 weeks | Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures. Note: * Culture conversion requires at least 2 consecutive culture negative/positive samples at least 7 days apart. * Participants who are documented at a visit as unable to produce sputum and who are clinically considered to be responding well to treatment will be considered to be culture negative at that visit. |
| Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | End of Treatment, 26 weeks | Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures. |
Countries
Georgia, Moldova, Russia, South Africa
Participant flow
Recruitment details
A total of 248 participants were screened for the trial, of whom 67 failed screening, 181 were randomized, and 169 completed treatment.
Participants by arm
| Arm | Count |
|---|---|
| 1200mg L x 26 Weeks + Pa + B 2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks | 45 |
| 1200 mg L x 9 Weeks + Pa + B 2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks | 46 |
| 600 mg L x 26 Weeks + Pa + B 1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks | 45 |
| 600 mg L x 9 Weeks + Pa + B 1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks | 45 |
| Total | 181 |
Baseline characteristics
| Characteristic | 1200 mg L x 9 Weeks + Pa + B | 600 mg L x 26 Weeks + Pa + B | 1200mg L x 26 Weeks + Pa + B | 600 mg L x 9 Weeks + Pa + B | Total |
|---|---|---|---|---|---|
| Age, Continuous | 35.1 years | 39.2 years | 37.4 years | 36.8 years | 37.1 years |
| Alcohol Use Current | 8 Participants | 8 Participants | 8 Participants | 10 Participants | 34 Participants |
| Alcohol Use Former | 25 Participants | 19 Participants | 16 Participants | 24 Participants | 84 Participants |
| Alcohol Use Never | 13 Participants | 18 Participants | 21 Participants | 11 Participants | 63 Participants |
| BMI | 21.3 kg/m^2 | 21.3 kg/m^2 | 20.8 kg/m^2 | 21.9 kg/m^2 | 21.3 kg/m^2 |
| Chest x-ray at Screening Abnormal | 44 Participants | 44 Participants | 43 Participants | 43 Participants | 174 Participants |
| Chest x-ray at Screening Normal | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 7 Participants |
| Chest X-ray Cavities at Screening Bilateral | 4 Participants | 13 Participants | 5 Participants | 6 Participants | 28 Participants |
| Chest X-ray Cavities at Screening None | 21 Participants | 12 Participants | 18 Participants | 18 Participants | 69 Participants |
| Chest X-ray Cavities at Screening Unilateral | 21 Participants | 20 Participants | 22 Participants | 21 Participants | 84 Participants |
| Current Tuberculosis (TB) type Extensively Drug Resistant (XDR) TB | 18 Participants | 19 Participants | 21 Participants | 17 Participants | 75 Participants |
| Current Tuberculosis (TB) type Multi Drug Resistant (MDR) TB (nonresponsive) | 5 Participants | 2 Participants | 2 Participants | 3 Participants | 12 Participants |
| Current Tuberculosis (TB) type Multi Drug Resistant (MDR) TB (treatment-intolerant) | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 9 Participants |
| Current Tuberculosis (TB) type Pre-Extensively Drug Resistant (Pre-XDR) TB | 22 Participants | 22 Participants | 19 Participants | 22 Participants | 85 Participants |
| Height | 170.2 cm | 171.2 cm | 173.2 cm | 171.2 cm | 171.4 cm |
| History of Tuberculosis (TB) Drug Sensitive (DS) TB | 13 participants | 18 participants | 16 participants | 7 participants | 54 participants |
| History of Tuberculosis (TB) MDR TB | 23 participants | 21 participants | 20 participants | 25 participants | 89 participants |
| History of Tuberculosis (TB) Mono Resistant TB | 0 participants | 1 participants | 0 participants | 1 participants | 2 participants |
| History of Tuberculosis (TB) Pre-XDR TB | 5 participants | 6 participants | 6 participants | 7 participants | 24 participants |
| History of Tuberculosis (TB) XDR TB | 28 participants | 28 participants | 25 participants | 25 participants | 106 participants |
| HIV Status Negative | 37 Participants | 36 Participants | 36 Participants | 36 Participants | 145 Participants |
| HIV Status Positive | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 36 Participants |
| Karnofsky performance status 100 | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 8 Participants |
| Karnofsky performance status 60 or below | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Karnofsky performance status 70 | 2 Participants | 4 Participants | 3 Participants | 4 Participants | 13 Participants |
| Karnofsky performance status 80 | 13 Participants | 10 Participants | 13 Participants | 11 Participants | 47 Participants |
| Karnofsky performance status 90 | 30 Participants | 29 Participants | 28 Participants | 26 Participants | 113 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 21 Participants | 11 Participants | 16 Participants | 66 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 24 Participants | 34 Participants | 29 Participants | 115 Participants |
| Region of Enrollment Georgia | 8 Participants | 5 Participants | 13 Participants | 8 Participants | 34 Participants |
| Region of Enrollment Moldova | 4 Participants | 1 Participants | 2 Participants | 3 Participants | 10 Participants |
| Region of Enrollment Russia | 16 Participants | 18 Participants | 19 Participants | 18 Participants | 71 Participants |
| Region of Enrollment South Africa | 18 Participants | 21 Participants | 11 Participants | 16 Participants | 66 Participants |
| Screening smear microscopy for Acid Fast Bacilli (AFB) 1+ | 7 Participants | 4 Participants | 4 Participants | 6 Participants | 21 Participants |
| Screening smear microscopy for Acid Fast Bacilli (AFB) 2+ | 6 Participants | 3 Participants | 6 Participants | 4 Participants | 19 Participants |
| Screening smear microscopy for Acid Fast Bacilli (AFB) 3+ | 5 Participants | 7 Participants | 1 Participants | 10 Participants | 23 Participants |
| Screening smear microscopy for Acid Fast Bacilli (AFB) No AFB seen | 24 Participants | 23 Participants | 23 Participants | 20 Participants | 90 Participants |
| Screening smear microscopy for Acid Fast Bacilli (AFB) Scanty positive | 4 Participants | 8 Participants | 11 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Female | 16 Participants | 14 Participants | 15 Participants | 14 Participants | 59 Participants |
| Sex: Female, Male Male | 30 Participants | 31 Participants | 30 Participants | 31 Participants | 122 Participants |
| Smoking Current | 22 Participants | 17 Participants | 15 Participants | 12 Participants | 66 Participants |
| Smoking Former | 9 Participants | 12 Participants | 10 Participants | 16 Participants | 47 Participants |
| Smoking Never | 15 Participants | 16 Participants | 20 Participants | 17 Participants | 68 Participants |
| Time to positive at baseline | 11.3 days | 14.0 days | 14.3 days | 12.5 days | 13.0 days |
| Weight | 62.1 kg | 63.1 kg | 62.8 kg | 64.5 kg | 63.1 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 1 / 46 | 0 / 45 | 0 / 45 | 1 / 181 |
| other Total, other adverse events | 40 / 45 | 41 / 46 | 39 / 45 | 36 / 45 | 156 / 181 |
| serious Total, serious adverse events | 3 / 45 | 4 / 46 | 1 / 45 | 3 / 45 | 11 / 181 |
Outcome results
Primary
Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment
Unfavourable status: 1. Participants not classified as having achieved or maintained culture negative status when last seen 2. Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture 3. Participants who had a positive culture not followed by at least two negative cultures when last seen 4. Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide 5. Participants definitely or possibly dying from TB related cause during the follow-up phase 6. Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy 7. Participants who have had surgery and the resected tissue is cultured and is positive for MTB 8. Participants lost to follow up or withdrawn from the study before the end of treatment
Time frame: 26 weeks
Population: Participants were considered unassessable and therefore excluded from the Modified Intent to Treat (MITT) population if they were late exclusions, lost to follow-up, reinfected with a different strain of TB, withdrawn during the Follow-up Period, or died during the treatment period.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1200mg L x 26 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Unfavorable | 3 Participants |
| 1200mg L x 26 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Favorable | 41 Participants |
| 1200 mg L x 9 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Favorable | 40 Participants |
| 1200 mg L x 9 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Unfavorable | 5 Participants |
| 600 mg L x 26 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Unfavorable | 4 Participants |
| 600 mg L x 26 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Favorable | 41 Participants |
| 600 mg L x 9 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Favorable | 37 Participants |
| 600 mg L x 9 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Unfavorable | 7 Participants |
| Total | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Unfavorable | 19 Participants |
| Total | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment | Favorable | 159 Participants |
Secondary
Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment.
Unfavourable status: 1. Participants not classified as having achieved or maintained culture negative status when last seen 2. Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture 3. Participants who had a positive culture not followed by at least two negative cultures when last seen 4. Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide 5. Participants definitely or possibly dying from TB related cause during the follow-up phase 6. Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy 7. Participants who have had surgery and the resected tissue is cultured and is positive for MTB 8. Participants lost to follow up or withdrawn from the study before the end of treatment
Time frame: 78 weeks
Population: Participants were considered unassessable and therefore excluded from the Modified Intent to Treat (MITT) population if they were late exclusions, lost to follow-up, reinfected with a different strain of TB, withdrawn during the Follow-up Period, or died during the treatment period.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1200mg L x 26 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Unfavorable | 3 Participants |
| 1200mg L x 26 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Favorable | 40 Participants |
| 1200 mg L x 9 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Unfavorable | 5 Participants |
| 1200 mg L x 9 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Favorable | 39 Participants |
| 600 mg L x 26 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Unfavorable | 5 Participants |
| 600 mg L x 26 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Favorable | 40 Participants |
| 600 mg L x 9 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Favorable | 35 Participants |
| 600 mg L x 9 Weeks + Pa + B | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Unfavorable | 9 Participants |
| Total | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Unfavorable | 22 Participants |
| Total | Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment. | Favorable | 154 Participants |
Secondary
Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline
Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures.
Time frame: End of Treatment, 26 weeks
Population: The participant numbers for inclusion in analysis are those assessable participants with a positive culture status at baseline, not including those who withdrew or were lost to contact during treatment at or before Week 26.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1200mg L x 26 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Positive | 0 Participants |
| 1200mg L x 26 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Negative | 29 Participants |
| 1200mg L x 26 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Died | 0 Participants |
| 1200 mg L x 9 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Positive | 1 Participants |
| 1200 mg L x 9 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Negative | 28 Participants |
| 1200 mg L x 9 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Died | 0 Participants |
| 600 mg L x 26 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Positive | 1 Participants |
| 600 mg L x 26 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Negative | 31 Participants |
| 600 mg L x 26 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Died | 0 Participants |
| 600 mg L x 9 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Negative | 31 Participants |
| 600 mg L x 9 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Positive | 1 Participants |
| 600 mg L x 9 Weeks + Pa + B | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Died | 0 Participants |
| Total | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Positive | 3 Participants |
| Total | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Died | 0 Participants |
| Total | Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline | Negative | 119 Participants |
Secondary
Time to Sputum Culture Conversion to Negative Status Through the Treatment Period
Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures. Note: * Culture conversion requires at least 2 consecutive culture negative/positive samples at least 7 days apart. * Participants who are documented at a visit as unable to produce sputum and who are clinically considered to be responding well to treatment will be considered to be culture negative at that visit.
Time frame: 26 weeks
Population: Participants in the MITT population who were culture positive during the baseline period were assessable. Unassessable Includes participants not positive at baseline and/or unassessable in the MITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1200mg L x 26 Weeks + Pa + B | Time to Sputum Culture Conversion to Negative Status Through the Treatment Period | 4 weeks |
| 1200 mg L x 9 Weeks + Pa + B | Time to Sputum Culture Conversion to Negative Status Through the Treatment Period | 4 weeks |
| 600 mg L x 26 Weeks + Pa + B | Time to Sputum Culture Conversion to Negative Status Through the Treatment Period | 6 weeks |
| 600 mg L x 9 Weeks + Pa + B | Time to Sputum Culture Conversion to Negative Status Through the Treatment Period | 6 weeks |
| Total | Time to Sputum Culture Conversion to Negative Status Through the Treatment Period | 6 weeks |