The mean time to culture conversion was 57 days [17]. A modified intention to treat analysis at 24 weeks showed that the rate of culture conversion was 79.5%. Table 5 Summary of third Phase 2 trial: Study C209 (unpublished data [17]) Study sites Inclusion criteria for patients Exclusion criteria Study design and intervention Number of MDR patients (BDQ + OBR) Findings 33 sites in Asia, South Africa, Eastern BIBW2992 molecular weight Europe, South

America Newly and previously diagnosed smear positive patients with either:  (a) MDR-TB (39.9%)  (b) pre-XDR-TB (18.9%)  (c) XDR (15.9%) . As for Table 3, except patients with HIV with a CD4 count <250 cells/μL were excluded Single arm study  (a) 24 weeks of OBR and BDQ (400 mg daily for 2 weeks then 200 mg 3 times per week), Then,  (b) Individualized

18-month to 24-month treatment for MDR-TB. 233 (205a) Culture conversion up to 24 weeks  (a) Median time to culture conversion, using time-point of 24 weeks: 57 days  (b) Culture conversion (mITTa): 79.5% Mortality BDQ + OBR (12/205, 5.6%), up to trial reporting cut-offb Onset of death: median 376 days since last intake of study drug [17] BDQ bediquiline, HIV human immunodeficiency virus, MDR multi-drug resistant, mITT modified intention to treat, OBR optimized background regimen, TB tuberculosis, XDR extensively drug resistant amITT: Only 205 patients were included in a ‘modified intention to treat analysis’ (excluding DS TB and people with no DST result) bThe final study follow-up data has not yet been reported [17] Clinical Evidence for Safety of Bedaquiline Pooled safety data are available from the first and second Phase 2 studies [17]. Overall, 96.1% Ensartinib concentration of 102 subjects receiving bedaquiline and 95.2% of the 105 subjects receiving placebo reported at least one adverse event [17]. Adverse events with a prevalence of more than find more 10% in the pooled analysis of the first and second Phase 2 studies are presented in Table 6 [17, 62]. There was no overall difference in the incidence of these adverse events between groups, after accounting for multiple testing. In the two studies, 27.5% of subjects taking

bedaquiline and 22.9% of subjects taking placebo experienced grade 3 or 4 adverse events of any kind [17]. The most common of these events was hyperuricemia, which occurred in 10.8% of patients taking bedaquiline and 13.3% of patients taking placebo. Table 6 Adverse events of any grade, reported in at least 10% of subjects in the first and second Phase 2 studies   Up to 24-week follow-up All follow-ups In patients taking BDQ for 24 weeksa In patients taking placebo for 24 weeksa In all patients taking BDQ In all patients taking placebo n = 79 n = 81 n = 102 n = 105 n (%) n (%) n (%) n (%) Any adverse event 77 (97.5) 77 (95.1) 98 (96.1) 100 (95.2) Gastrointestinal disorders 50 (63.3) 50 (61.7) 59 (57.8) 59 (56.2)  Nausea 30 (38.0) 26 (32.1) 36 (35.3) 27 (25.7)  Vomiting 20 (25.3) 21 (25.9) 21 (20.6) 24 (22.9)  Upper abdominal pain 9 (11.4) 7 (8.6) 10 (9.