First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug.
J Antimicrob Chemother
; 79(6): 1353-1361, 2024 06 03.
Article
en En
| MEDLINE
| ID: mdl-38656557
ABSTRACT
BACKGROUND:
The clinical candidate alpibectir augments the activity of, and overcomes resistance to, the anti-TB drug ethionamide in vitro and in vivo.OBJECTIVES:
A Phase 1, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK) and food effect of alpibectir administered as single and multiple oral doses in healthy volunteers (NCT04654143).METHODS:
Eighty participants were randomized. In single ascending dose (SAD), a total of six dose levels of alpibectir (0.5 to 40â mg) were tested under fasted and fed (10â mg) conditions as single daily doses in sequential cohorts. In multiple ascending dose (MAD), repeat doses (5 to 30â mg) were administered once daily for 7â days in three sequential cohorts.RESULTS:
No serious adverse event was reported. Thirteen participants across groups experienced a total of 13 mild or moderate treatment-emergent adverse events. Alpibectir showed rapid absorption after single dose (mean Tmax range of 0.88 to 1.53â h). Food affected the PK of alpibectir, characterized by a slower absorption (mean Tmax 3.87â h), a lower Cmax (-17.7%) and increased AUC0-t (+19.6%) compared with the fasted condition. Following repeat dosing, dose proportionality was shown for both Cmax and AUC0-tau. Accumulation of alpibectir was observed across all doses, with a more profound effect on AUC during a dosing interval (AUC0-tau) compared with Cmax (1.8- and 1.3-fold on average), respectively. Steady state was considered to have been achieved by Day 7 of dosing.CONCLUSIONS:
Alpibectir was generally well tolerated, and no clinically relevant safety findings were identified in the participants treated during SAD or MAD. The PK is dose-proportional and affected by food.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Voluntarios Sanos
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Antituberculosos
Límite:
Adolescent
/
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suiza