Initial 24 week phase randomized to either:  (a) BDQ + OBR (400 mg daily for 2 weeks then 200 mg 3 times per week for 22 weeks) OR  (b) Placebo + OBR alone 161a (80/81) Culture conversion up to 24 weeksb [17]  (a) Time

to sputum culture conversion using time point of 24 weeks (primary end point): BDQ + OBR < OBR: HR 2.44 (95% CI 1.57, 3.80) P < 0.001c  (b) Proportion of sputum culture conversions at 24 weeks: BDQ + OBR (52/66, 78.8%) > OBR Selleck Copanlisib alone (38/66, 57.6%), P = 0.008   Drug susceptible TB or XDR-TB Then, 2. Followed by 18–24 months of standard MDR-TB treatment   Culture conversion up to 72 weeksb [17]  Proportion sputum cultures converted at 72 weeks: BDQ + OBR (47/66,

71.2%) > OBR alone (37/66, 56.1%), P = 0.069         Mortality  BDQ + OBR (10/80, 12.5%) > OBR (2/81, 2.5%), P = 0.015**** Onset of death: median 313 days [17] BDQ bedaquiline, DST drug susceptibility testing, HR hazard ratio, MDR-TB multi-drug-resistant tuberculosis, OBR optimized EPZ5676 supplier background regimen, which comprises a five-drug regimen for MDR-TB, including fluoroquinolones, aminoglycosides, pyrazinamide, ethionamide, ethambutol, and/or cycloserine/terizidone, TB tuberculosis, XDR-TB extensively drug-resistant tuberculosis **** P value calculated using Pearson’s χ 2 test (uncorrected), from available data. Analyses listed here based on modified intention to treat that excludes patients who had negative cultures at baseline, or were found to not meet inclusion criteria due to DST results after randomization aOne patient in BDQ group not commenced on treatment after randomization bModified intention to treat analysis cAdjusted for lung cavitations and study center A modified intention to treat analysis showed that culture conversion during the first buy Hydroxychloroquine 24 weeks was faster in the

group with bedaquiline than the control group (83 days versus 125 days, HR 2.44 [95% CI 1.57, 3.80], P < 0.0001) [17], but there was no significant difference between the treatment groups in this outcome at 72 weeks (P = 0.069) [17]. During the 2-year follow-up, three patients in the bedaquiline group and seven in the control group experienced treatment failure. Third Phase 2 Study of Bedaquiline Preliminary results are also available from a third, uncontrolled study of 233 patients enrolled at 33 sites in Asia, South Africa, Eastern Europe, and South America (Study C209). These data also appeared only in the US FDA submission [17]. This study gave bedaquiline to patients with newly diagnosed or previously treated patients with either MDR-TB or XDR-TB (where the isolate was sensitive to at least three drugs other than bedaquiline).