Bedaquiline for multidrug-resistant TB in paediatric patients
Publication Date
2021
Document Type
Article
Publication Title
The International Journal of Tuberculosis and Lung Disease
Abstract
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 toyears) 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–years; approved adult tablet at the adult dosage) and Cohort 2 (≥5–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, andnoQTcF >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–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.
First Page
716
Last Page
724
APA Citation
Moodliar, R., Aksenova, V., Frias, M. G., van de Logt, J., Rossenu, S., Birmingham, E., Zhuo, S., Mao, G., Lounis, N., Kambili, C., & Bakare, N. (2021). Bedaquiline for multidrug-resistant TB in paediatric patients. The International Journal of Tuberculosis and Lung Disease, 25(9), 716-724. DOI:10.5588/ijtld.21.0022