Pharmacokinetics and safety of TBAJ-587, a novel antimycobacterial diarylquinoline, in healthy participants
5 affiliations
- 1Global Alliance for TB Drug Development, New York, New York, USA
- 2QPS Netherlands BV, Groningen, the Netherlands
- 3Vast Therapeutics, Morrisville, North Carolina, USA
- 4IdiPAZ, University Hospital La Paz, Servicio Madrileño de Salud (SERMAS), Madrid, Spain
- 5Department of Clinical Pharmacy and Pharmacology, University Medical Center, Groningen, the Netherlands
Abstract
TBAJ-587 is a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile than the first-generation bedaquiline. It is currently under development for the treatment of drug-susceptible and drug-resistant tuberculosis. A first-in-human trial of TBAJ-587, including single and multiple ascending oral doses and a dedicated food-effect cohort, was conducted in 92 healthy adults. Plasma exposures of TBAJ-587 were generally linear for AUCtau and slightly subproportional for Cmax, with the major circulating active metabolite, M3, remaining low relative to the parent. A high-fat meal increased the mean Cmax and AUClast 3.46- and 2.26-fold, respectively. TBAJ-587 accumulated with multiple dosing over the 28-day period, with mean accumulation ratios across the three tested doses ranging from 1.69 to 2.32 for Cmax and from 2.74 to 3.73 for AUCtau. However, steady-state conditions were not yet reached on day 28. Mean terminal half-lives after 28-day dosing of TBAJ-587 ranged from approximately 80 to 111 days. There were no deaths or serious adverse events, and TBAJ-587 was generally safe and well tolerated at single doses of 25–800 mg under fasting conditions and multiple doses of 50–200 mg once daily for 28 days after a standard breakfast. In addition, no dose- or time-dependent effects were noted for any of the other safety and tolerability parameters, including no clinically significant effects on the QTc interval. These results support further investigation of TBAJ-587 for the treatment of tuberculosis.
CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04890535.
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BibTeX
@article{nedelman2026pharmacokinetics,
title = {{Pharmacokinetics and safety of TBAJ-587, a novel antimycobacterial diarylquinoline, in healthy participants}},
author = {Jerry Nedelman and Almari Conradie and Antonio Lombardi and Dean Hickman and Khalid Abd-Elaziz and Peter Dogterom and Paul Bruinenberg and Antonio J. Carcas Sansuán and Elly Sakiman and Zuzana Diamant and Jolanda van Duinen and Maria Beumont and Eugene Sun},
journal = {Antimicrobial Agents and Chemotherapy},
year = {2026},
month = jul,
doi = {10.1128/aac.01930-25},
url = {https://doi.org/10.1128/aac.01930-25},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pharmacokinetics and safety of TBAJ-587, a novel antimycobacterial diarylquinoline, in healthy participants
AU - Jerry Nedelman
AU - Almari Conradie
AU - Antonio Lombardi
AU - Dean Hickman
AU - Khalid Abd-Elaziz
AU - Peter Dogterom
AU - Paul Bruinenberg
AU - Antonio J. Carcas Sansuán
AU - Elly Sakiman
AU - Zuzana Diamant
AU - Jolanda van Duinen
AU - Maria Beumont
AU - Eugene Sun
PY - 2026
DA - 2026/07/28
JO - Antimicrobial Agents and Chemotherapy
DO - 10.1128/aac.01930-25
UR - https://doi.org/10.1128/aac.01930-25
AB - TBAJ-587 is a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile than the first-generation bedaquiline. It is currently under development for the treatment of drug-susceptible and drug-resistant tuberculosis. A first-in-human trial of TBAJ-587, including single and multiple ascending oral doses and a dedicated food-effect cohort, was conducted in 92 healthy adults. Plasma exposures of TBAJ-587 were generally linear for AUCtau and slightly subproportional for Cmax, with the major circulating active metabolite, M3, remaining low relative to the parent. A high-fat meal increased the mean Cmax and AUClast 3.46- and 2.26-fold, respectively. TBAJ-587 accumulated with multiple dosing over the 28-day period, with mean accumulation ratios across the three tested doses ranging from 1.69 to 2.32 for Cmax and from 2.74 to 3.73 for AUCtau. However, steady-state conditions were not yet reached on day 28. Mean terminal half-lives after 28-day dosing of TBAJ-587 ranged from approximately 80 to 111 days. There were no deaths or serious adverse events, and TBAJ-587 was generally safe and well tolerated at single doses of 25–800 mg under fasting conditions and multiple doses of 50–200 mg once daily for 28 days after a standard breakfast. In addition, no dose- or time-dependent effects were noted for any of the other safety and tolerability parameters, including no clinically significant effects on the QTc interval. These results support further investigation of TBAJ-587 for the treatment of tuberculosis. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04890535.
SN - 0066-4804
SN - 1098-6596
ER -