Last updated: 01/16/2025 13:40:38

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
Other
Other
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 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 percentage of 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
    Primary completion date:
    2024-14-01
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    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
    Other
    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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