First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug
Pieren, Michel (BioVersys AG)
Abáigar Gutierrez-Solana, Ana (Ibaizabal Bidea)
Antonijoan Arbós, Rosa Ma (Rosa María) (Institut de Recerca Sant Pau)
Boyle, Gary W. (GlaxoSmithKline)
Davila, Myriam (BioVersys AG)
Davy, Maria (BioVersys AG)
Gitzinger, Marc (BioVersys AG)
Husband, Lisa (BioVersys AG)
Martínez-Martínez, María S. (GlaxoSmithKline)
Ochoa Mazarro, Dolores (Instituto de Investigación Sanitaria la Princesa)
Pefani, Eleni (GlaxoSmithKline)
Penman, Sophie L. (GlaxoSmithKline)
Remuiñán, Modesto J. (GlaxoSmithKline)
Vlasakakis, Georgios (GlaxoSmithKline)
Zeitlinger, Markus (Medical University of Vienna)
Dale, Glenn E. (BioVersys AG)
Universitat Autònoma de Barcelona

Fecha:	2024
Resumen:	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). Eighty participants were randomized. In single ascending dose (SAD), a total of six dose levels of alpibectir (0. 5 to 40 mg) were tested under fasted and fed (10 mg) conditions as single daily doses in sequential cohorts. In multiple ascending dose (MAD), repeat doses (5 to 30 mg) were administered once daily for 7 days in three sequential cohorts. 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. 53 h). Food affected the PK of alpibectir, characterized by a slower absorption (mean Tmax 3. 87 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. 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.
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Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Administration, Oral ; Adolescent ; Adult ; Antitubercular Agents ; Double-Blind Method ; Drug-Related Side Effects and Adverse Reactions ; Female ; Food-Drug Interactions ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; Placebos ; Young Adult
Publicado en:	Journal of antimicrobial chemotherapy, Vol. 79 Núm. 6 (january 2024) , p. 1353-1361, ISSN 1460-2091

DOI: 10.1093/jac/dkae107
PMID: 38656557

9 p, 523.7 KB

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