Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants

Summary

This study is the first to test GSK3494245 in humans, to evaluate its safety, tolerability, and pharmacokinetics (PK) after a single dose. It involves 3 groups of participants and has a crossover design where each participant received a maximum of 3 ascending oral doses of GSK3494245 and 1 placebo dose under fasted conditions. The first 2 Cohorts received up to 3 increasing doses of the drug and 1 dose of a placebo under fasted conditions, within each period, according to the randomization schedule, in a blinded manner. Cohort 3 is comprised of a 2-way crossover which includes 1 dosing regimen under fasted then fed conditions and 1 regimen under fed then fasted conditions in a 1:1 ratio.

Timeline

Start

2020-09-29

Primary completion

2024-01-14

Completion

2024-01-14

Outcome

Outcome not reported

Stopped: “Further development of GSK3494245 has been halted based on assessment of clinical data indicating that predicted efficacious doses cannot be achieved in line with dosing requirements outlined in the target product profile for the proposed indication.”

Publications

• Moodley M, Kostapanos M, Iavarone L, Bracher M, Lavezzi SM, Davy M, Singh P, Bhat R, Wong D, Sharma H, Tan LK, Miles TJ. Safety and pharmacokinetics of GSK3494245, a highly selective Leishmaniasis kinetoplastid proteasome inhibitor for the treatment of visceral leishmaniasis: A Phase 1, randomized, single ascending dose escalation study in healthy participants. PLoS Negl Trop Dis. 2026 May 13;20(5):e0014181. doi: 10.1371/journal.pntd.0014181. eCollection 2026 May.

Drugs

Indications