Open AccessBedaquiline for multidrug-resistant TB in paediatric patients
Author(s) -
Ronelle Moodliar,
Valentina Aksenova,
Melchior Frias,
J. van de Logt,
Stefaan Rossenu,
Eileen Birmingham,
S Zhuo,
Gary Mao,
Nacer Lounis,
Chrispin Kambili,
Nyasha Bakare
Publication year - 2021
Publication title -
the international journal of tuberculosis and lung disease/the international journal of tuberculosis and lung disease. articles traduits en français ...
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.103
H-Index - 110
eISSN - 1815-7920
pISSN - 1027-3719
DOI - 10.5588/ijtld.21.0022
Subject(s) - medicine , bedaquiline , cohort , tolerability , tuberculosis , adverse effect , regimen , pharmacokinetics , culture conversion , surgery , mycobacterium tuberculosis , pulmonary tuberculosis , pathology
BACKGROUND: TMC207-C211 (NCT02354014) is a Phase 2, open-label, multicentre, single-arm study to evaluate pharmacokinetics, safety/tolerability, antimycobacterial activity and dose selection of bedaquiline (BDQ) in children (birth to <18 years) with multidrug-resistant-TB (MDR-TB). METHODS: Patients received 24 weeks' BDQ with an anti-MDR-TB background regimen (BR), followed by 96 weeks of safety follow-up. Results of the primary analysis are presented based on data up to 24 weeks for Cohort 1 (≥12-<18 years; approved adult tablet at the adult dosage) and Cohort 2 (≥5-<12 years; age-appropriate 20 mg tablet at half the adult dosage). RESULTS: Both cohorts had 15 patients, of whom respectively 53% and 40% of Cohort 1 and Cohort 2 children had confirmed/probable pulmonary MDR-TB. Most patients completed 24 weeks´ BDQ/BR treatment (Cohort 1: 93%; Cohort 2: 67%). Geometric mean BDQ area under the curve 168h values of 119,000 ng.h/mL (Cohort 1) and 118,000 ng.h/mL (Cohort 2) at Week 12 were within 60-140% (86,200-201,000 ng.h/mL) of adult target values. Few adverse event (AE) related discontinuations or serious AEs, and no QTcF >460 ms during BDQ/BR treatment or deaths occurred. Of MGIT-evaluable patients, 6/8 (75%) Cohort 1 and 3/3 (100%) Cohort 2 culture converted. CONCLUSION: In children and adolescents aged ≥5-<18 years with MDR-TB, including pre-extensively drug-resistant-TB (pre-XDR-TB) or XDR-TB, 24 weeks of BDQ provided a comparable pharmacokinetic and safety profile to adults.