Safety, tolerability and pharmacokinetics (PK) investigation of GSK3494245 in healthy participants
Trial overview
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
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)
- 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.
- Participant must have been 18 to lesser than or equal to (<=) 55 years of age, at the time of signing the informed consent.
- Participant must have been healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) which was/were not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may have been included only if the Investigator in consultation with the Medical Monitor (if required) agreed and documented that the finding was unlikely to introduce additional risk factors and was not going to interfere with the study procedures.
- Body weight greater than or equal to (>=) 50 kg and body mass index (BMI) within the range 18.5-28 kg per meter square (kg/m^2) (inclusive).
- Male participants only. A male participant with a female partner of reproductive potential must have agreed to use contraception during the intervention period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed consent form (ICF) and protocol. Exclusion criteria
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- Abnormal blood pressure, as determined by the investigator.
- Previous history of leishmaniasis.
- Alanine transaminase (ALT) greater than (>) upper limit of normal (ULN) at screening or Day
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Current or history of clinically significant gastritis or gastroduodenal ulcers or regular use of non-steroidal anti-inflammatory drugs (NSAID).
- Consumption of more than 14 units/week alcohol.
- Current or history of change in taste or smell without any plausible clinical explanation based on investigator's clinical judgement.
- QTc >450 milliseconds (msec) based on average of triplicate ECGs.
- Waveform abnormalities including premature ventricular contraction (PVC) triplets and more than 500 single PVCs in 24 hours, or any other abnormalities at the discretion of investigator.
- Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
- Past or intended use of over-the-counter or prescription medication, including herbal medications, NSAIDs, proton pump inhibitors (PPIs) or anti-histamine 2 receptor (H2) antagonists within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing. Other concomitant medication may have been considered on a case by case basis by the investigator in consultation with the medical monitor. Paracetamol is permitted (capped to <=2 grams/day).
- Participation in the study that would result in loss of blood or blood products in excess of 500 mL within a 56-day period.
- Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
- Current enrollment or past participation in this clinical study.
- Participants with renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) with an age appropriate Glomerular filtration rate (GFR) <90 (milliliter per minute per 1.73 meter square [mL/min/1.73m^2]).
- Screening urine albumin: creatinine ratio >30 milligram per gram (mg/g) (>3 milligram per millimole [mg/mmol])
- Presence of hepatitis B surface antigen (HBsAg) test result at screening.
- Positive hepatitis C antibody test result at screening.
- Positive hepatitis C Ribonucleic acid (RNA) test result at screening.
- Positive human immunodeficiency virus (HIV) antibody test.
- Presence of clinically significant hematuria and/or proteinuria.
- Carbon monoxide levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 3 months prior to screening.
- Positive pre-study drug/alcohol screen.
- Regular use of known drugs of abuse.
- Fed regimens only: Participant must have had no dietary restrictions (e.g., lactose intolerance) or inability to eat an adapted standard meal (includes 35-40% fat content).
- Fed regimen only: History of gall bladder surgery or gall bladder removal, or history of an acute disease state (e.g. cholelithiasis) within 14 days prior to receiving the study treatment. Inability to eat gelatin for bile sampling cohort.
- Participants must not have travelled to an area (as determined by the investigator) with a high prevalence of leishmanial/parasitic infections in the 6 months before screening or intend to do so in the 3 months after the final dose of study treatment.
- Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates participation in the study.
- A positive laboratory confirmation of corona virus disease 2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.
Inclusion criteria
1. Total bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN was acceptable if total bilirubin was fractionated and direct bilirubin less than (<) 35 percent [%]).
Trial location(s)
Study documents
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Plain language summaries
To view plain language summaries on trialsummaries.com click here.