Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants
- Registration Number
- NCT04504435
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This is a Phase 1, double-blind, randomized, placebo-controlled, first time in human (FTIH) study to assess the safety, tolerability and PK of a single dose of GSK3494245. The study will consist of 3 cohorts, conducted in a sequential manner. Cohorts 1 and 2 will consist of a single ascending dose (SAD), crossover design where each participant will receive a maximum of 3 ascending oral doses of GSK3494245 and 1 placebo dose under fasted conditions. At each dose level, GSK3494245 and placebo will be administered in a 3:1 ratio, within each period, according to the randomization schedule in a blinded manner. Cohort 3 will comprise 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. The fed conditions will investigate the effect of safety, tolerability and PK of a single dose of GSK3494245 following food administration.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 59
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Participants in Cohort 2 GSK3494245 Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with dose level (DL) 5 and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant. Cohort 3: Participants receiving GSK3494245 (fed then fasted) GSK3494245 Participants will receive the DLX of GSK3494245 in the fed state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fasted state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant. Participants in Cohort 1 Placebo Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with 20 milligram (mg) and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant. Participants in Cohort 1 GSK3494245 Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with 20 milligram (mg) and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant. Participants in Cohort 2 Placebo Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with dose level (DL) 5 and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant. Cohort 3: Participants receiving GSK3494245 (fasted then fed) GSK3494245 Participants will receive the selected dose level (DLX) of GSK3494245 in the fasted state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fed state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.
- Primary Outcome Measures
Name Time Method Number of participants with abnormal cardiac telemetry findings Up to 24 hours post dose on Day 1 Telemetry is the continuous monitoring of a participants heart rate and rhythm from a remote location. Continuous cardiac telemetry will start in a supine position after at least 5 minutes rest.
Number of participants with clinically significant abnormal findings in vital signs Up to 14 days post last dose in each treatment period Number of participants with abnormal vital signs will be assessed.
Number of participants with clinically significant abnormal findings in Electrocardiogram (ECG) Parameters Up to 14 days post last dose in each treatment period Triplicate 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS interval, QT interval, Corrected QT (QTc) interval.
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Up to 14 days post last dose in each treatment period 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. SAE is defined as any untoward medical occurrence that, at any dose: results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Number of participants with clinically significant abnormal findings in clinical chemistry parameters Up to 14 days post last dose in each treatment period Blood samples will be collected for the assessment of chemistry parameters
Number of participants with treatment emergent AEs and SAEs Up to 14 days post last dose in each treatment period Treatment emergent AE and SAE are any untoward medical occurrences in a clinical study participant, having causal relation with the use of a study intervention.
Number of participants with clinically significant abnormal findings in hematology parameters Up to 14 days post last dose in each treatment period Blood samples will be collected for the assessment of hematology parameters.
Number of participants with urinalysis findings Up to 14 days post last dose in each treatment period Urine samples will be collected for the assessment of urinalysis parameters.
- Secondary Outcome Measures
Name Time Method Area under the plasma drug concentration (AUC) versus time curve (AUC[0-t]) of GSK3494245 following single dose administration under fasting condition Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 minutes [min], 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fasting condition.
AUC (0-inf) of GSK3494245 following single dose administration under fed condition Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245 under fed condition.
Cmax of GSK3494245 following single dose administration under fed condition Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fed condition.
Dose-proportionality assessment using Cmax following single dose of GSK3494245 Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245.
AUC-time curve from time zero to extrapolated to infinity (AUC[0-inf]) of GSK3494245 following single dose administration under fasting condition Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate AUC (0-inf) of GSK3494245 under fasting condition.
Maximum observed plasma drug concentration (Cmax) of GSK3494245 following single dose administration under fasting condition Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fasting condition.
Tmax of GSK3494245 following single dose administration under fed condition Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fed condition.
Apparent terminal half-life (t1/2) of GSK3494245 following single dose administration under fasting condition Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
t1/2 of GSK3494245 following single dose administration under fed condition Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
Fraction of dose excreted in urine over 24 hours (fe%) of GSK3494245 following single dose administration Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Urine samples will be collected at the indicated time points to evaluate fe% of GSK3494245
Dose-proportionality assessment using AUC(0-inf) following single dose of GSK3494245 Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245.
AUC (0-t) of GSK3494245 following single dose administration under fed condition Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fed condition.
Time to maximum observed plasma drug concentration (Tmax) of GSK3494245 following single dose administration under fasting condition Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fasting condition.
Amount of GSK3494245 excreted in urine over 24 hours (Ae0-24h) following single dose administration Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Urine samples will be collected at the indicated time points to evaluate Ae0-24h of GSK3494245.
Renal Clearance (CLr) of GSK3494245 following single dose administration Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period) Urine samples will be collected at the indicated time points to evaluate CLr of GSK3494245.
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Cambridge, United Kingdom