What question did this study set out to answer?

May 17, 2026Open Access

Randomized, Placebo‐Controlled, First‐in‐Human Study of the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Oral Doses of Novel Antitubercular Drug Candidate, GSK2556286, in Healthy Adults

Puntos clave

This study aims to assess the safety, tolerability, pharmacokinetics, and food effect of GSK2556286, a novel antitubercular drug.
Randomized, placebo-controlled design; 56 participants received single doses of GSK2556286; 19 received placebo.
Repeat dosing with GSK2556286 (up to 650 mg) administered once daily for 14 days in part B, assessing safety and pharmacokinetics.
ClinicalTrials.gov identifier: NCT04472897; stopping criterion based on clinically significant adverse events.
Single doses of GSK2556286 were well tolerated; all reported adverse events were mild except for moderate AEs at 1000 mg.
In part B, one severe adverse event was reported and four out of six participants in the 650 mg cohort discontinued due to multiple adverse events.
Termination of the study was due to unexpected pharmacokinetic variability and exposure-related adverse events.

Resumen

Abstract This first‐in‐human study (ClinicalTrials.gov identifier: NCT04472897) evaluated the safety, tolerability, pharmacokinetics, and food effect of single ascending and repeat oral doses of GSK2556286 (GSK286), a novel antitubercular drug candidate with efficacy in animal models of tuberculosis. In part A, 56 participants received single GSK286 doses (25–1000 mg; 10 cohorts) and 19 participants received a placebo. In part B, GSK286 and placebo doses were administered once daily for up to 14 days. Cohorts received repeat doses of GSK286 (225 or 650 mg; 13 participants) or placebo (four participants) in part B before the study was placed on hold due to reaching the stopping criterion, defined as clinically significant, non‐serious adverse events (AEs) that are considered to be at least possibly related to GSK286 in two or more participants on active treatment. Single GSK286 doses were well tolerated; all reported AEs were mild, apart from moderate AEs in two participants administered GSK286 1000 mg, and there were no serious AEs (SAEs). In part B (repeat dosing), three participants reported moderate AEs, one reported a severe AE, and there were no SAEs. However, four of six participants in the 650 mg repeat dose cohort discontinued treatment due to the AEs (at least one) of headache, photophobia, fatigue, nausea, and vomiting. There was high intraindividual variability in the pharmacokinetics of GSK286 in both parts of the study, and the effect of food in modulating this variability was unclear. The combination of unexpected pharmacokinetic variability and exposure‐related AEs led to termination of the study.

Preguntar a la IA

Me gusta

Guardar

Ver artículo completo