Safety, efficacy, and pharmacokinetics of bedaquiline in Japanese patients with pulmonary multidrug-resistant tuberculosis: An interim analysis of an open-label, phase 2 study.

Background: Bedaquiline, a diarylquinoline with a novel mode of action that specifically inhibits mycobacterial adenosine 5'-triphosphate (ATP) synthase, has been approved in over 50 countries including the USA and EU for the treatment of pulmonary multidrug-resistant tuberculosis (pMDR-TB) in adults. Methods: This study was conducted to evaluate the safety, efficacy, and pharmacokinetics of bedaquiline in adult Japanese patients with pMDR-TB. In this study, patients received bedaquiline for 24 weeks or more (maximum 48 weeks) with an individualized background regimen (BR). Efficacy was assessed as the time to sputum culture conversion after the initiation of bedaquiline treatment. Results: Treatment-emergent adverse events (TEAEs) were reported in 5/6 patients (83.3%) during the investigational phase (bedaquiline treatment + 1 week). The TEAEs observed in > 1 patient were hepatic function abnormal (4/6), hypoaesthesia (3/6), nasopharyngitis, acne, and nausea (2/6 each). The TEAEs leading to treatment discontinuation of bedaquiline were none. The time to sputum culture conversion was 14-15 days. Plasma bedaquiline C-max was achieved within 4-6 h of bedaquiline administration and AUC(24h) ranged from 50,637 to 107,300 ng*h/mL (5 patients) at week 2 and were 58,513 and 77,148 ng*h/mL (2 patients) at week 24. Conclusions: No new safety signals in patients, including those receiving bedaquiline with BR beyond 24 weeks, and the faster culture conversion time indicate that the administration of bedaquiline as part of a multi-drug regimen for at least 24 weeks is a suitable treatment for adult Japanese patients with pMDR-TB. (C) 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.