Safety,efficacy, and pharmacokinetics of bedaquiline in Japanese patients with pulmonary multidrug-resistant tuberculosis: An interim analysis of an open-label,phase 2 study |
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| Affiliation: | 1. Moscow Government''s Health Department, Moscow, Russian Federation;2. Istituti Clinici Scientifici Maugeri IRCCS, Via Roncaccio 16, 21049, Tradate, Italy;3. Public Health Consulting Group, Lugano, Switzerland;4. Queen Mary University, London, United Kingdom;5. Royal London Hospital, Barts Health NHS Trust, London, United Kingdom;6. University of Cape Town, Cape Town, South Africa;7. University of Groningen, Groningen, the Netherlands;8. P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, India;9. Solna Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden;10. University Hospital, Verona, Italy;11. University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia;12. Hospital Centre Vila Nova de Gaia and University of Porto, Porto, Portugal;13. Athens Chest Hospital, Athens, Greece;14. Northern State Medical University, Arkhangelsk, Russian Federation;15. Harry Surtie Hospital, Upington, South Africa;p. S. Bortolo Hospital, Vicenza, Italy;q. Medicins Sans Frontiers, Ukrainian Mission, Kiev, Ukraine;r. University Hospital, Strasbourg, France;s. Municipal Hospital F. J. Munĩz, Buenos Aires, Argentina;t. AOVV Eugenio Morelli Hospital, Sondalo, Italy;u. Athens Chest Hospital, Ministry of Health, Athens, Greece;v. Galliera Hospital, Genoa, Italy;w. District Clinical Specialist Team, Namakwa District, Springbok, South Africa;x. University of Insubria, Varese, Italy;y. University of Sassari, Italy |
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| Abstract: | BackgroundBedaquiline, 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.MethodsThis 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.ResultsTreatment-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 Cmax was achieved within 4–6 h of bedaquiline administration and AUC24h 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.ConclusionsNo 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. |
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| Keywords: | Bedaquiline Japanese Multidrug-resistant tuberculosis Sputum culture conversion |
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