Last updated: 05/15/2026 11:50:17

Safety, tolerability and pharmacokinetics (PK) investigation of GSK3494245 in healthy participants

GSK study ID
208441
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: 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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of participants with adverse events (AEs)

Timeframe: From Day 1 (first dose) up to 14 days post last dose in each treatment period

Number of participants with serious adverse events (SAEs)

Timeframe: From the signing of the informed consent form (a period starting up to 28 days before the first dose on Day 1) to up to 14 days after the last dose of each treatment period

Number of participants with treatment emergent AEs (TEAEs) and treatment emergent SAEs

Timeframe: From Day 1 (first dose) up to 2 days post last dose in each treatment period

Summary of change from baseline in hematology parameters: basophils, neutrophils, eosinophils, lymphocytes, monocytes and platelets

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in hematology parameters: mean corpuscular volume

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in hematology parameters: mean corpuscular hemoglobin

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in hematology parameters: erythrocytes and reticulocytes

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in hematology parameters: hemoglobin

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in hematology parameters: hematocrit and reticulocytes

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in clinical chemistry parameters: alanine aminotransferase (ALT), alkaline phosphate (ALP), aspartate aminotransferase (AST), creatine phosphokinase (CPK), and gamma glutamyl transferase (GGT)

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in clinical chemistry parameters: albumin, protein

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in clinical chemistry parameters: bicarbonate, calcium corrected for albumin, glucose, lactic acid, magnesium, phosphate, potassium, sodium, triglycerides, and urea

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in clinical chemistry parameters: bilirubin, creatinine, direct bilirubin

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in clinical chemistry parameters: C-reactive protein (CRP)

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in clinical chemistry parameters: pH

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Number of participants with worst-case urinalysis results

Timeframe: From Day 1 up to 14 Days post last dose

Summary of change from baseline in physical examinations: body mass index (BMI)

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in vital signs: respiratory rate

Timeframe: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of change from baseline in vital signs: supine diastolic blood pressure, supine systolic blood pressure

Timeframe: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of change from baseline in vital signs: supine pulse rate

Timeframe: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of change from baseline in vital signs: tympanic membrane temperature

Timeframe: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of change from baseline in physical examinations: weight

Timeframe: At Day 2 and Day 4 in each treatment period compared to Baseline

Summary of change from baseline in electrocardiogram (ECG) parameters: heart rate

Timeframe: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Summary of change from baseline in ECG parameters: PR interval, QRS interval, QT interval, corrected QT (QTc) interval, QT interval corrected using Bazett's formula, QT interval corrected, using Fridericia's formula

Timeframe: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)

Number of participants with abnormal cardiac telemetry findings

Timeframe: Up to 24 hours post first dose on Day 1

Secondary outcomes:

Area under the plasma drug concentration (AUC) versus time curve (AUC[0-t]) of GSK3494245 following single dose administration, under fasting conditions

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

AUC (0-t) of GSK3494245 following single dose administration under fed conditions

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

AUC-time curve from time zero to extrapolated to infinity (AUC[0-inf]) of GSK3494245 following single dose administration under fasting condition

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

AUC (0-inf) of GSK3494245 following single dose administration under fed conditions

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

Maximum observed plasma drug concentration (Cmax) of GSK3494245 following single dose administration under fasting conditions

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

Cmax of GSK3494245 following single dose administration under fed conditions

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

Time to maximum observed plasma drug concentration (Tmax) of GSK3494245 following single dose administration under fasting conditions

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

Tmax of GSK3494245 following single dose administration under fed conditions

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

Apparent terminal half-life (t1/2) of GSK3494245 following single dose administration under fasting conditions

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

t1/2 of GSK3494245 following single dose administration under fed conditions

Timeframe: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)

Dose-proportionality assessment using AUC(0-inf) following a single dose of GSK3494245

Timeframe: At Day 1 (post-dose)

Dose-proportionality assessment using Cmax following single dose of GSK3494245

Timeframe: At Day 1 (post-dose)

Interventions:
Drug: GSK3494245
Drug: Placebo
Enrollment:
59
Observational study model:
Not applicable
Primary completion date:
2024-14-01
Time perspective:
Not applicable
Clinical publications:
Moodley M, Kostapanos M, Iavarone L, Bracher M, Lavezzi S, Davy M, et al. . GH_208441 GSK245_PhI FTIH Ms_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_(AR). PLoS Negl Trop Dis. PMID:42127151 DOI:10.1371/journal.pntd.0014181
Medical condition
Leishmaniasis
Product
GSK3494245
Collaborators
NA
Study date(s)
September 2020 to January 2024
Type
Interventional
Phase
1

Participation criteria

Sex
Male
Age
18 - 55 Years
Accepts healthy volunteers
Yes
  • Inclusion criteria
  • Participant must have been 18 to lesser than or equal to (<=) 55 years of age, at the time of signing the informed consent.

Trial location(s)

Location
Status
Contact us
Contact us
Location
GSK Investigational Site
Cambridge, United Kingdom, CB2 2GG
Status
Study Complete

Study documents

Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status
Terminated (halted prematurely)
Actual primary completion date
2024-14-01
Actual study completion date
2024-14-01

Plain language summaries

Summary of results in plain language
Available language(s): English

To view plain language summaries on trialsummaries.com click here.

Additional information about the trial

Additional information
Not applicable
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