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

NCT04504435 | Terminated Phase 1 Results DMC

• 2 other identifiers: 2084412019-004492-39
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leishmaniasis

Keywords

GSK3494245; Leishmaniasis; Single Ascending Dose; First Time in Human; Pharmacokinetics

Outcome Measures

Primary Outcomes (25)

• 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 Outcomes (12)

• Area Under the Plasma Drug Concentration (AUC) Versus Time Curve (AUC[0-t]) of GSK3494245 Following Single Dose Administration, Under Fasting Conditions

  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

  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

  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

  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

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

Study Arms (20)

Cohort 1 Treatment Sequence (Seq) 1: GSK3494245 20 milligram (mg) fasted/Placebo (PBO)

EXPERIMENTAL

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; Drug: Placebo

Cohort 1 Treatment Seq 2: PBO/GSK3494245 40mg fasted

EXPERIMENTAL

Participants received Placebo during dosing period 1 and 40 mg of GSK3494245 during dosing period 2 under fasted conditions, at Day 1.

Drug: GSK3494245; Drug: Placebo

Cohort 1 Treatment Seq 3: GSK3494245 20mg fasted/GSK3494245 40mg fasted

EXPERIMENTAL

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

Cohort 1 Treatment Seq 4: GSK3494245 20mg fasted/GSK3494245 40mg fasted

EXPERIMENTAL

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

Cohort 2 Treatment Seq 1:GSK3494245 40mg fasted/GSK3494245 80mg fasted/GSK3494245 120mg fasted/PBO

EXPERIMENTAL

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; Drug: Placebo

Cohort 2 Treatment Seq 2:GSK3494245 40mg fasted/GSK3494245 80mg fasted/PBO/GSK3494245 160mg fasted

EXPERIMENTAL

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; Drug: Placebo

Cohort 2 Treatment Seq 3:GSK3494245 40mg fasted/PBO/GSK3494245 120mg fasted/GSK3494245 160mg fasted

EXPERIMENTAL

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; Drug: Placebo

Cohort 2 Treatment Seq 4: PBO/GSK3494245 80mg fasted/GSK3494245 120mg fasted/GSK3494245 160mg fasted

EXPERIMENTAL

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; Drug: Placebo

Cohort 2A Treatment Seq 1: GSK3494245 150mg fasted

EXPERIMENTAL

Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.

Drug: GSK3494245

Cohort 2A Treatment Seq 2: GSK3494245 150mg fasted

EXPERIMENTAL

Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.

Drug: GSK3494245

Cohort 2A Treatment Seq 3: GSK3494245 150mg fasted

EXPERIMENTAL

Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.

Drug: GSK3494245

Cohort 2A Treatment Seq 4: PBO fasted

EXPERIMENTAL

Participants received Placebo during dosing period 1 under fasted conditions, at Day 1.

Drug: Placebo

Cohort 3 Treatment Seq 1: PBO fed/PBO fasted/GSK3494245 80mg fasted/GSK3494245 80mg fed

EXPERIMENTAL

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; Drug: Placebo

Cohort 3 Treatment Seq 2: PBO fasted/GSK3494245 80mg fed/PBO fed/GSK3494245 80mg fasted

EXPERIMENTAL

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; Drug: Placebo

Cohort 3 Treatment Seq 3: GSK3494245 80mg fed/GSK3494245 80mg fasted/PBO fasted/PBO fed

EXPERIMENTAL

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; Drug: Placebo

Cohort 3 Treatment Seq 4: GSK3494245 80mg fasted/PBO fed/GSK3494245 80mg fed/PBO fasted

EXPERIMENTAL

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; Drug: Placebo

Cohort 3A Treatment Seq 1: PBO fed/GSK3494245 240mg fed

EXPERIMENTAL

Participants received placebo in fed conditions during dosing period 1 and 240 mg of GSK3494245 in fed conditions during dosing period 2.

Drug: GSK3494245; Drug: Placebo

Cohort 3A Treatment Seq 2: GSK3494245 160mg fed/PBO fed

EXPERIMENTAL

Participants received 160 mg of GSK3494245 in fed conditions during dosing period 1 and Placebo in fed conditions during dosing period 2.

Drug: GSK3494245; Drug: Placebo

Cohort 3A Treatment Seq 3: GSK3494245 160mg fed/GSK3494245 240mg fed

EXPERIMENTAL

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

Cohort 3A Treatment Seq 4: GSK3494245 160mg fed/GSK3494245 240mg fed

EXPERIMENTAL

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

Interventions

GSK3494245 DRUG

Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.

Cohort 1 Treatment Seq 2: PBO/GSK3494245 40mg fasted; Cohort 1 Treatment Seq 3: GSK3494245 20mg fasted/GSK3494245 40mg fasted; Cohort 1 Treatment Seq 4: GSK3494245 20mg fasted/GSK3494245 40mg fasted; Cohort 1 Treatment Sequence (Seq) 1: GSK3494245 20 milligram (mg) fasted/Placebo (PBO); Cohort 2 Treatment Seq 1:GSK3494245 40mg fasted/GSK3494245 80mg fasted/GSK3494245 120mg fasted/PBO; Cohort 2 Treatment Seq 2:GSK3494245 40mg fasted/GSK3494245 80mg fasted/PBO/GSK3494245 160mg fasted; Cohort 2 Treatment Seq 3:GSK3494245 40mg fasted/PBO/GSK3494245 120mg fasted/GSK3494245 160mg fasted; Cohort 2 Treatment Seq 4: PBO/GSK3494245 80mg fasted/GSK3494245 120mg fasted/GSK3494245 160mg fasted; Cohort 2A Treatment Seq 1: GSK3494245 150mg fasted; Cohort 2A Treatment Seq 2: GSK3494245 150mg fasted; Cohort 2A Treatment Seq 3: GSK3494245 150mg fasted; Cohort 3 Treatment Seq 1: PBO fed/PBO fasted/GSK3494245 80mg fasted/GSK3494245 80mg fed; Cohort 3 Treatment Seq 2: PBO fasted/GSK3494245 80mg fed/PBO fed/GSK3494245 80mg fasted; Cohort 3 Treatment Seq 3: GSK3494245 80mg fed/GSK3494245 80mg fasted/PBO fasted/PBO fed; Cohort 3 Treatment Seq 4: GSK3494245 80mg fasted/PBO fed/GSK3494245 80mg fed/PBO fasted; Cohort 3A Treatment Seq 1: PBO fed/GSK3494245 240mg fed; Cohort 3A Treatment Seq 2: GSK3494245 160mg fed/PBO fed; Cohort 3A Treatment Seq 3: GSK3494245 160mg fed/GSK3494245 240mg fed; Cohort 3A Treatment Seq 4: GSK3494245 160mg fed/GSK3494245 240mg fed

Placebo DRUG

Matching placebo capsules were provided

Cohort 1 Treatment Seq 2: PBO/GSK3494245 40mg fasted; Cohort 1 Treatment Sequence (Seq) 1: GSK3494245 20 milligram (mg) fasted/Placebo (PBO); Cohort 2 Treatment Seq 1:GSK3494245 40mg fasted/GSK3494245 80mg fasted/GSK3494245 120mg fasted/PBO; Cohort 2 Treatment Seq 2:GSK3494245 40mg fasted/GSK3494245 80mg fasted/PBO/GSK3494245 160mg fasted; Cohort 2 Treatment Seq 3:GSK3494245 40mg fasted/PBO/GSK3494245 120mg fasted/GSK3494245 160mg fasted; Cohort 2 Treatment Seq 4: PBO/GSK3494245 80mg fasted/GSK3494245 120mg fasted/GSK3494245 160mg fasted; Cohort 2A Treatment Seq 4: PBO fasted; Cohort 3 Treatment Seq 1: PBO fed/PBO fasted/GSK3494245 80mg fasted/GSK3494245 80mg fed; Cohort 3 Treatment Seq 2: PBO fasted/GSK3494245 80mg fed/PBO fed/GSK3494245 80mg fasted; Cohort 3 Treatment Seq 3: GSK3494245 80mg fed/GSK3494245 80mg fasted/PBO fasted/PBO fed; Cohort 3 Treatment Seq 4: GSK3494245 80mg fasted/PBO fed/GSK3494245 80mg fed/PBO fasted; Cohort 3A Treatment Seq 1: PBO fed/GSK3494245 240mg fed; Cohort 3A Treatment Seq 2: GSK3494245 160mg fed/PBO fed

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: A male participant with a female partner of reproductive potential had to agree 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.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must have been 18 to lesser than or equal to (\<=) 55 years of age, at the time of signing the informed consent.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

MeSH Terms

Conditions

Leishmaniasis

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of sequential and cross-over (SAD part, within cohort) groups.

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 7, 2020
• Study Start: September 29, 2020
• Primary Completion: January 14, 2024
• Study Completion: January 14, 2024
• Last Updated: May 1, 2026
• Results First Posted: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

GB (1)