Tuberculosis
Conditions
Interventions
M-Pa-Z 400mg/200mg/1500mg
HRZE / HR
M-Pa-Z 400mg/100mg/1500mg
M-Pa-Z 400mg/200mg/1500mg MDR-TB
Sponsors
Global Alliance for TB Drug Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial-related procedures. 2. Male or female, aged 18 years or over. 3. Body weight (in light clothing and no shoes) ¿ 30 kg. 4. Sputum positive for tubercule bacilli (at least 1+ on the IUATLD/WHO scale (Appendix 1)) on smear microscopy at the trial laboratory. 5. Drug-Sensitive TB treatment arms subjects should be: a. sensitive to rifampicin by rapid sputum based test (may be sensitive or resistant to isoniazid) AND b. either newly diagnosed for TB or have a patient history of being untreated for at least 3 years after cure from a previous episode of TB. If they are entered into the trial due to being sensitive to rifampicin by rapid sputum based test, however on receipt of the rifampicin resistance testing using an indirect susceptibility test in liquid culture this shows they are rifampicin resistant, they will be: a. Excluded as late exclusions; b. Possibly replaced as determined by the sponsor. MDR-TB treatment arm subjects should be resistant to rifampicin by rapid sputum based test (may be sensitive or resistant to isoniazid). 6. A chest x-ray which in the opinion of the investigator is compatible with pulmonary TB. 7. Be of non-childbearing potential or using effective methods of birth control.
Exclusion criteria
Exclusion criteria: 1. Any non TB related condition that could compromise the well-being of the subject. 2. Being or about to be treated for Malaria. 3. Is critically ill & has a diagnosis likely to result in death. 4. TB meningitis or other forms of extrapulmonary TB 5. History of allergy or hypersensitivity to any of the trial IMP 6. For HIV infected subjects any of the following: a. CD4+ count 450 ms; c. History of additional risk factors for Torsade de Pointes: d. Any clinically significant ECG abnormality. 11. Unstable Diabetes Mellitus which required hospitalization for hyper- or hypo-glycaemia within the past year prior to screening. 12. Previous treatment with PA-824. 13. For DS-TB: Previous treatment for tuberculosis within 3 years prior to screening. For the MDR-TB: Previous treatment for MDR-TB. 14. Any diseases in which the use of the std TB drugs is contra-indicated. 15. Use of any drug within 30 days prior to randomisation known to prolong QTc interval. 16. Use of systemic glucocorticoids /= grade 2 b. CrCl level /= grade 3 e. serum potassium /= grade 3 g. ALT >/= grade 3 h. ALP grade 4 i. total bilirubin: o > 2.0 x ULN, when other liver functions are in the normal range o >1.50 x ULN when accompanied by any increase in other liver function tests
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of bacteriologic failure or relapse or clinical failure at 12 months from the start of therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety and Tolerability;Mycobacterial Characterization ;Pharmacokinetics (PK) and Pharmacokinetics-Pharmacodynamics (PK-PD):;Mycobacterial Characterization ;Pharmacokinetics (PK) and Pharmacokinetics-Pharmacodynamics (PK-PD):;Efficacy | — |
Countries
Kenya, South Africa, Tanzania, Uganda, Zambia
Contacts
Public ContactMary-Anne Bopape
Regulatory Affairs
Outcome results
None listed