Trial reportPLoS neglected tropical diseases2026
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.
Trial report in PLoS neglected tropical diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04504435 (A Randomized, Double-blind, Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single), which is not on this map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-blind, Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single (in Both Fed and Fasted States) Doses of GSK3494245 in Healthy Participants
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVisceral leishmaniasis (VL) is a neglected tropical disease caused by kinetoplastid parasites. If left untreated, VL has a case fatality >90%, making treatment essential for patient survival. Existing therapies have several limitations that impact treatment outcomes, including toxicity, requirement for parenteral administration, long treatment duration, and development of parasite resistance, driving the need for newer therapies. This Phase 1 first-time-in-human study evaluated the tolerability, safety, and pharmacokinetics (PK) of GSK3494245, a novel highly selective Leishmania kinetoplastid proteasome inhibitor. METHODOLOGY: This was a randomized, double-blind, placebo-controlled, single ascending dose study evaluating the oral administration of GSK3494245 in healthy participants aged 18 to ≤55 years (NCT04504435). The study was conducted at a single center in the United Kingdom between October 2020 and January 2024.
findingsGSK3494245 had an acceptable safety profile following administration of single doses of up to 240 mg in healthy male participants. All adverse events (AEs) were considered resolved or recovered, with most AEs being of mild or moderate severity. One serious AE of mild tachycardia was reported. The increase in exposure was slightly more than dose-proportional and approximately proportional under fasted and fed conditions, respectively. The median time to reach the maximum plasma concentration (Cmax) ranged from 0.50 to 1.79 hours, and the geometric mean of the elimination half-life ranged from 1.04 to 2.27 hours. Two participants met the Cmax stopping criterion.
conclusionGSK3494245 showed an acceptable safety profile over the dose range studied. However, based on its observed PK profile, GSK3494245 is unlikely to achieve the effective dose while ensuring safe exposure within the once- or twice-daily monotherapy target product profile recommended by the Drugs for Neglected Diseases initiative. CLINICAL
trial registrationNCT Number (www.clinicaltrials.gov): NCT04504435 EudraCT, CTIS: 2019-004492-39.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.