Clofazimine pharmacokinetics in novel rifampicin-resistant tuberculosis regimens: an analysis of the endTB and endTB-Q trials

@misc{ngara2026clofazimine,
  title = {{Clofazimine pharmacokinetics in novel rifampicin-resistant tuberculosis regimens: an analysis of the endTB and endTB-Q trials}},
  author = {B. Ngara and B. P.Solans and E. Yang and P. Van Brantegem and L. Guglielmetti and F. Varaine and M. Gouillou and C. D. Mitnick and A. N. LaHood and M. L. Rich and K. J. Seung and L. Wiesner and L. Hans and R. Swart and A. Abubakirov and K. Khazhidinov and A. Belgozhanova and S. Mpinda and S. Mohale and D. Holtzman and D. Vargas Vasquez and F. Garcia Velarde and S. Mucching Toscano and A. Aftab and M. S. Arshad and A. Ashraf and D. V. Luong and H. T. Nguyen and H. T. Phan and S. Wasserman and N. Ntuli and R. Savic and H. McIlleron and G. E. Velasquez},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.18.26363422},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.18.26363422v1},
  note = {CC BY},
}

TY  - UNPB
TI  - Clofazimine pharmacokinetics in novel rifampicin-resistant tuberculosis regimens: an analysis of the endTB and endTB-Q trials
AU  - B. Ngara
AU  - B. P.Solans
AU  - E. Yang
AU  - P. Van Brantegem
AU  - L. Guglielmetti
AU  - F. Varaine
AU  - M. Gouillou
AU  - C. D. Mitnick
AU  - A. N. LaHood
AU  - M. L. Rich
AU  - K. J. Seung
AU  - L. Wiesner
AU  - L. Hans
AU  - R. Swart
AU  - A. Abubakirov
AU  - K. Khazhidinov
AU  - A. Belgozhanova
AU  - S. Mpinda
AU  - S. Mohale
AU  - D. Holtzman
AU  - D. Vargas Vasquez
AU  - F. Garcia Velarde
AU  - S. Mucching Toscano
AU  - A. Aftab
AU  - M. S. Arshad
AU  - A. Ashraf
AU  - D. V. Luong
AU  - H. T. Nguyen
AU  - H. T. Phan
AU  - S. Wasserman
AU  - N. Ntuli
AU  - R. Savic
AU  - H. McIlleron
AU  - G. E. Velasquez
PY  - 2026
DA  - 2026/09/18
PB  - medRxiv
DO  - 10.64898/2026.09.18.26363422
UR  - https://www.medrxiv.org/content/10.64898/2026.09.18.26363422v1
AB  - IntroductionRifampicin-resistant tuberculosis poses a significant threat worldwide. Clofazimine is considered important for the construction of effective individualized multidrug regimens to treat rifampicin-resistant tuberculosis. Our goal was to characterize clofazimine pharmacokinetics in novel combination treatment regimens and to identify participant characteristics associated with variations in drug exposure.  MethodsClofazimine pharmacokinetic data were obtained from adults and adolescents enrolled in the PandrTB pharmacokinetic sub-study of the endTB and endTB-Q Phase 3 randomized controlled therapeutic trials for rifampicin-resistant tuberculosis. Plasma concentrations were analyzed using nonlinear mixed-effects modeling to quantify clofazimine exposure and explore the impact of relevant covariates.  Results100 participants from six countries with high burdens of rifampicin-resistant tuberculosis contributed pharmacokinetic data. Their median age was 34 years, 32% were female, 18% were living with diabetes mellitus, and 18% were living with HIV. Clofazimine plasma concentration values were best described by a 2-compartment pharmacokinetic model with first-order absorption. Co-administration with delamanid and HIV co-infection resulted in a 37% increase and 20% decrease in clofazimines bioavailability, respectively. Diabetes was associated with a 43% decrease in clofazimine clearance. Clofazimine remained in the body for a median of 2.5 years (95th percentile: 0.5 - 8) following 9 months of treatment.  ConclusionCo-administration with delamanid, diabetes mellitus, and HIV were associated with variation in clofazimine exposure. We estimated that clofazimine remained present in the body for longer than two years in over half of participants following 9 months of treatment. Follow-up studies are recommended to confirm these associations before adjusting clofazimine dose or clinical care decisions.
ER  -