Health Condition 1: null- Multi-Drug Resistant Pulmonary Tuberculosis
Conditions
Interventions
Intervention1: Regimen 1:PA-824,Moxifloxacin and Pyrazinamide: After randomization subjects will be administered Regimen 1, 2 or 3 as per the randomization list.
After the first 8 weeks (study treatme
Sponsors
Open Source Drug Discovery of The Council of Scientific and Industrial Research
Eligibility
Inclusion criteria
Inclusion criteria: A patient will be eligible for entry to the study if all the following conditions are satisfied: 1. Male aged 18 â?? 65 years (both ages inclusive). 2. Is willing to give written informed consent to be enrolled in the trial. 3. Weighs at least 30 kg. 4. Has newly diagnosed pulmonary MDR-TB (defined as a subject with MDR-TB who has never been treated for MDR-TB before or has been treated with only first-line TB drugs [Isoniazid, Rifampin, Ethambutol, Pyrazinamide or streptomycin]). 5. Is willing to have an HIV test. 6. Agrees to use effective barrier contraception during the period of the study and for a further period of 3 months. 7. Has an identifiable address and expects to remain in the area for the duration of the study and follow-up. 8. Is willing to be hospitalized during the study period of 8 weeks. This is to ensure compliance with medications, specimen collection and close monitoring for safety. 9. Is willing to adhere to the study procedures and follow-up schedule. 10. Is willing to discontinue all TB drugs to allow 7-days washout before baseline assessments and starting treatment.
Exclusion criteria
Exclusion criteria: A patient will not be eligible for entry to the study if he: 1. Has received prior treatment for MDR-TB with any second line drug of any duration (except streptomycin) 2. Is infected with a strain of M. Tuberculosis resistant to a second-line injectable drug or to a fluoroquinolone by Line Probe Assay (LPA). 3. Is resistant to Pyrazinamide by Mycobacterial Growth Indicator Tube (MGIT) method. 4. Has clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator. 5. Has any evidence of renal impairment. 6. Has clinical icterus or hepatic impairment. 7. Has a history and/ or presence (or evidence) of neuropathy or epilepsy. 8. Is unable to take oral medication. 9. Has any condition (social or medical) which in the opinion of the Investigator would make study participation unreliable or unsafe. 10. Is taking any medications contraindicated with the medicines in the study regimens. 11. Has a known allergy to any of the drugs proposed to be used in the study regimens. 12. Has a history of or current clinically relevant cardiovascular disorder. Family history of sudden death of unknown or cardiac related cause, or of prolonged QTc interval. Concomitant use of any drug known to prolong QTc interval . 13. Has clinically relevant changes in the electrocardiogram (ECG). 14. Has diabetes mellitus and HbA1C value exceeding 6. 15. Has evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities. 16. Has a known or suspected current history within the past two years of alcohol or drug abuse. 17. Is sero-positive for HIV infection. 18. Has evidence of cataract, chorioretinitis, optic neuritis, or uveitis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The rate of change in time to sputum culture positivity (TTP) through 8 weeks in the MGIT culture system in patients treated with: a. a combination of PA-824, Moxifloxacin and Pyrazinamide b. PA-824 plus Category IV regimen of RNTCP c. Category IV regimen of RNTCP Timepoint: 8 weeks active treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) Proportion of patients with negative sputum culture at 8 weeks, 2) Time to sputum conversion to negative, 3) Grade III and IV drug adverse events, and 4) PK of study drugs in the 3 study regimens Timepoint: 8 weeks | — |
Countries
India
Contacts
Public ContactDr Sarala Balachandran
National Institute of Tuberculosis and Respiratory Diseases (NITRD)
Outcome results
None listed