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

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

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.

Study Overview

• Status: Terminated
• Conditions: Leishmaniasis
• Intervention / Treatment: Drug: GSK3494245; Drug: Placebo

Detailed Description

The study originally planned to include 2 parts - a single ascending doses (SAD) part and a multiple ascending doses (MAD) part, incorporating a food effect component to investigate the influence of food on the PK of GSK3494245. However, only the SAD part was conducted due to a decision to terminate the study early.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 2GG
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 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 - 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 [%]).
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

20

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 Treatment Sequence (Seq) 1: GSK3494245 20 milligram (mg) fasted/Placebo (PBO); Participants received 20 mg of GSK3494245 during dosing period 1 and Placebo matching the active dose amount during dosing period 2 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 1 Treatment Seq 2: PBO/GSK3494245 40mg fasted; Participants received Placebo during dosing period 1 and 40 mg of GSK3494245 during dosing period 2 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 1 Treatment Seq 3: GSK3494245 20mg fasted/GSK3494245 40mg fasted; Participants received 20 mg of GSK3494245 during dosing period 1 and 40 mg of GSK3494245 during dosing period 2 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Experimental: Cohort 1 Treatment Seq 4: GSK3494245 20mg fasted/GSK3494245 40mg fasted; Participants received 20 mg of GSK3494245 during dosing period 1 and 40 mg of GSK3494245 during dosing period 2 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Experimental: Cohort 2 Treatment Seq 1:GSK3494245 40mg fasted/GSK3494245 80mg fasted/GSK3494245 120mg fasted/PBO; Participants received 40 mg of GSK3494245 during dosing period 1, 80 mg of GSK3494245 during dosing period 2, 120 mg of GSK3494245 during dosing period 3 and matching Placebo during dosing period 4 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 2 Treatment Seq 2:GSK3494245 40mg fasted/GSK3494245 80mg fasted/PBO/GSK3494245 160mg fasted; Participants received 40 mg of GSK3494245 during dosing period 1, 80 mg of GSK3494245 during dosing period 2, matching placebo during dosing period 3 and 160 mg of GSK3494245 during dosing period 4 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 2 Treatment Seq 3:GSK3494245 40mg fasted/PBO/GSK3494245 120mg fasted/GSK3494245 160mg fasted; Participants received 40 mg of GSK3494245 during dosing period 1, matching placebo during dosing period 2, 120 mg of GSK3494245 during dosing period 3 and 160 mg of GSK3494245 during dosing period 4 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 2 Treatment Seq 4: PBO/GSK3494245 80mg fasted/GSK3494245 120mg fasted/GSK3494245 160mg fasted; Participants received placebo during dosing period 1, 80 mg of GSK3494245 during dosing period 2, 120 mg of GSK3494245 during dosing period 3 and 160 mg of GSK3494245 during dosing period 4 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 2A Treatment Seq 1: GSK3494245 150mg fasted; Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Experimental: Cohort 2A Treatment Seq 2: GSK3494245 150mg fasted; Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Experimental: Cohort 2A Treatment Seq 3: GSK3494245 150mg fasted; Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Experimental: Cohort 2A Treatment Seq 4: PBO fasted; Participants received Placebo during dosing period 1 under fasted conditions, at Day 1.	Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 3 Treatment Seq 1: PBO fed/PBO fasted/GSK3494245 80mg fasted/GSK3494245 80mg fed; Participants received Placebo in fed conditions during dosing period 1, Placebo in fasted conditions during dosing period 2, 80 mg of GSK3494245 in fasted conditions during dosing period 3 and 80 mg of GSK3494245 in fed conditions during dosing period 4.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 3 Treatment Seq 2: PBO fasted/GSK3494245 80mg fed/PBO fed/GSK3494245 80mg fasted; Participants received Placebo in fasted conditions during dosing period 1, 80 mg of GSK3494245 in fed conditions during dosing period 2, placebo in fed conditions during dosing period 3 and 80 mg of GSK3494245 in fasted conditions during dosing period 4.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 3 Treatment Seq 3: GSK3494245 80mg fed/GSK3494245 80mg fasted/PBO fasted/PBO fed; Participants received 80 mg of GSK3494245 in fed conditions during dosing period 1, 80 mg of GSK3494245 in fasted conditions during dosing period 2, Placebo in fasted conditions during dosing period 3 and placebo in fed conditions during dosing period 4.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 3 Treatment Seq 4: GSK3494245 80mg fasted/PBO fed/GSK3494245 80mg fed/PBO fasted; Participants received 80 mg of GSK3494245 in fasted conditions during dosing period 1, Placebo in fed conditions during dosing period 2, 80 mg of GSK3494245 in fed conditions during dosing period 3 and placebo in fasted conditions during dosing period 4.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 3A Treatment Seq 1: PBO fed/GSK3494245 240mg fed; Participants received placebo in fed conditions during dosing period 1 and 240 mg of GSK3494245 in fed conditions during dosing period 2.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 3A Treatment Seq 2: GSK3494245 160mg fed/PBO fed; Participants received 160 mg of GSK3494245 in fed conditions during dosing period 1 and Placebo in fed conditions during dosing period 2.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.; Drug: Placebo; Matching placebo capsules were provided
Experimental: Cohort 3A Treatment Seq 3: GSK3494245 160mg fed/GSK3494245 240mg fed; Participants received 160 mg of GSK3494245 in fed conditions during dosing period 1 and 240 mg of GSK3494245 in fed conditions during dosing period 2.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Experimental: Cohort 3A Treatment Seq 4: GSK3494245 160mg fed/GSK3494245 240mg fed; Participants received 160 mg of GSK3494245 in fed conditions during dosing period 1 and 240 mg of GSK3494245 in fed conditions during dosing period 2.	Drug: GSK3494245; Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.	From Day 1 (first dose) up to 14 days post last dose in each treatment period
Number of Participants With Serious Adverse Events (SAEs)	A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.	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	A TEAE and treatment emergent SAE is considered any untoward medical occurrence in a clinical study participant, considered by the investigator to have a causal relationship with study treatment. A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.	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	Blood samples were collected for the assessment of the hematology parameters: basophils, neutrophils, eosinophils, lymphocytes, monocytes and platelets. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. Standard deviation (SD)=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Volume	Blood samples were collected for the assessment of the hematology parameters: mean corpuscular volume. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Hemoglobin	Blood samples were collected for the assessment of the hematology parameters: mean corpuscular hemoglobin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Erythrocytes and Reticulocytes	Blood samples were collected for the assessment of the hematology parameters: erythrocytes and reticulocytes. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.	At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Hemoglobin	Blood samples were collected for the assessment of the hematology parameters: hemoglobin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.	At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Hematocrit and Reticulocytes	Blood samples were collected for the assessment of the hematology parameters: hematocrit and reticulocytes. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.	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)	Blood samples were collected for the assessment of the clinical chemistry parameters: ALT, ALP, AST, CPK, and GGT. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.	At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Clinical Chemistry Parameters: Albumin, Protein	Blood samples were collected for the assessment of the clinical chemistry parameters: albumin and protein. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.	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	Blood samples were collected for clinical chemistry parameters: bicarbonate, calcium corrected for albumin, glucose, lactic acid, magnesium, phosphate, potassium, sodium, triglycerides, urea. Baseline was defined as the last non-missing pre-dose assessment for each cohort. Generally, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments on Day 1 lacked timing, the first recorded was used. If one Day 1 assessment lacked timing, the last available from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, Baseline was set to missing. Change from baseline is defined as post-dose value minus baseline value. SD=0.0000 indicates SD below the detectable assay limit, approximated to 0.0000.	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	Blood samples were collected for the assessment of the clinical chemistry parameters: bilirubin, creatinine, direct bilirubin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	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)	Blood samples were collected for the assessment of the clinical chemistry parameters: CRP. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Clinical Chemistry Parameters: pH	Blood samples were collected for the assessment of the clinical chemistry parameters: pH. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.	At Day 2 and Day 4 in each treatment period compared to Baseline
Number of Participants With Worst-case Urinalysis Results	Urine samples were collected for the assessment of urinalysis parameters, which include pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.	From Day 1 up to 14 Days post last dose
Summary of Change From Baseline in Physical Examinations: Body Mass Index (BMI)	Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Vital Signs: Respiratory Rate	Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	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	Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	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	Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	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	Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	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	Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.	At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate	Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.	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	Triplicate 12-lead ECGs were obtained using an ECG machine that automatically measured the PR interval, QRS interval, QT interval, and QTc interval. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.	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	Telemetry is defined as the continuous monitoring of a participant's heart rate and rhythm from a remote location.	Up to 24 hours post first dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Drug Concentration (AUC) Versus Time Curve (AUC[0-t]) of GSK3494245 Following Single Dose Administration, Under Fasting Conditions	AUC(0-t) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to the last measurable concentration.	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	AUC(0-t) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to the last measurable concentration.	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	AUC(0-inf) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to infinity.	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	AUC(0-inf) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to infinity	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	Cmax is defined as the maximum concentration of the drug in plasma.	At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Cmax of GSK3494245 Following Single Dose Administration Under Fed Conditions	Cmax is defined as the maximum concentration of the drug in plasma.	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	Tmax is defined as a measure of the time required to reach the maximum concentration of the drug.	At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Tmax of GSK3494245 Following Single Dose Administration Under Fed Conditions	Tmax is defined as a measure of the time required to reach the maximum concentration of the drug.	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	t1/2 is defined as the time required by the plasma concentration to decline by 50%.	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	t1/2 is defined as the time required by the plasma concentration to decline by 50%.	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	A power model was used to assess the dose proportionality. A slope of 1 indicates that PK increased linearly with the dose. A slope greater than 1 indicates that PK increased more than proportionally with increase in the dose.	At Day 1 (post-dose)
Dose-proportionality Assessment Using Cmax Following Single Dose of GSK3494245	A power model was used to assess the dose proportionality. A slope of 1 indicates that PK increased linearly with the dose. A slope greater than 1 indicates that PK increased more than proportionally with increase in the dose.	At Day 1 (post-dose)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2020
• Primary Completion (Actual): January 14, 2024
• Study Completion (Actual): January 14, 2024

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 7, 2020

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; First Time in Human; Single Ascending Dose; Leishmaniasis; GSK3494245
• Additional Relevant MeSH Terms: Vector Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Skin Diseases; Skin Diseases, Infectious; Skin Diseases, Parasitic; Euglenozoa Infections; Skin and Connective Tissue Diseases; Leishmaniasis
• Other Study ID Numbers: 208441; 2019-004492-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No