A Phase 1, Randomised, Double Blind Placebo-controlled, First Time in Human Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Oral Doses and Food Effect of GSK4024484 in Healthy Adult Participants.
Overview
- Phase
- Phase 1
- Intervention
- GSK4024484C
- Conditions
- Malaria, Falciparum
- Sponsor
- GlaxoSmithKline
- Enrollment
- 156
- Locations
- 1
- Primary Endpoint
- Percentage of participants reporting serious adverse events (SAEs) after single ascending doses
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
The primary purpose of the study is to characterise the safety of GSK4024484 in healthy participants within a controlled pharmacokinetic (PK) range.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent.
- •Participants who are considered healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac assessment.
- •A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion Criteria
- •, or outside the normal reference range for the population being studied, may be included only if the Investigator considers, that the finding is unlikely to introduce additional risk factors for the participant and will not interfere with the study procedures or endpoints.
- •ALT (Alanine transaminase) and AST (Aspartate transaminase) within the normal range at screening.
- •Total bilirubin within the normal range unless the participant is known to have Gilbert's syndrome.
- •Body weight ≥50kg, and BMI within the range 19 to 32 kilogram per square metre (kg/m\^2) inclusive.
- •Male participants and female participants who are not of child bearing potential.
- •The participant is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
- •Exclusion Criteria:
- •History or presence of cardiovascular (including hypertension), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders, capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data in the opinion of the investigator.
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •An average weekly alcohol intake of \>14 units a week within 6 months prior to the study. One unit is equivalent to 8 g of alcohol: a half-pint (\~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
Arms & Interventions
Optional Group
Participants may be included in this group, to allow flexibility if the dose escalation needs modification or a dose level needs to be added or repeated.
Intervention: GSK4024484C
6 mg single ascending dose (SAD) Group
Participants receive a 6 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: GSK4024484C
6 mg single ascending dose (SAD) Group
Participants receive a 6 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: Placebo
12 mg SAD Group
Participants receive a 12 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: GSK4024484C
12 mg SAD Group
Participants receive a 12 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: Placebo
24 mg SAD Group
Participants receive a 24 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: GSK4024484C
24 mg SAD Group
Participants receive a 24 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: Placebo
40 mg SAD Group
Participants receive a 40 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: GSK4024484C
40 mg SAD Group
Participants receive a 40 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: Placebo
60 mg SAD Group
Participants receive a 60 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: GSK4024484C
60 mg SAD Group
Participants receive a 60 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: Placebo
Optional Group
Participants may be included in this group, to allow flexibility if the dose escalation needs modification or a dose level needs to be added or repeated.
Intervention: Placebo
80 mg SAD Group
Participants receive a 80 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: GSK4024484C
80 mg SAD Group
Participants receive a 80 mg single dose of GSK4024484 or matching placebo, in a fasted state.
Intervention: Placebo
Food Effect Group
Participants receive a single study dose of either GSK4024484 or matching placebo in a fed state.
Intervention: GSK4024484C
Food Effect Group
Participants receive a single study dose of either GSK4024484 or matching placebo in a fed state.
Intervention: Placebo
100 mg SAD Group
Participants receive a 100 mg single dose of GSK4024484 or matching placebo.
Intervention: GSK4024484C
100 mg SAD Group
Participants receive a 100 mg single dose of GSK4024484 or matching placebo.
Intervention: Placebo
10 mg multiple ascending doses (MAD) Group
Participants receive a single dose of 10 mg per day of GSK4024484 or matching placebo during 3 subsequent days (30 mg total).
Intervention: GSK4024484C
10 mg multiple ascending doses (MAD) Group
Participants receive a single dose of 10 mg per day of GSK4024484 or matching placebo during 3 subsequent days (30 mg total).
Intervention: Placebo
20 mg MAD Group
Participants receive a single dose of 20 mg per day of GSK4024484 or matching placebo during 3 subsequent days (60 mg total).
Intervention: GSK4024484C
20 mg MAD Group
Participants receive a single dose of 20 mg per day of GSK4024484 or matching placebo during 3 subsequent days (60 mg total).
Intervention: Placebo
30 mg MAD Group
Participants receive a single dose of 30 mg per day of GSK4024484 or matching placebo during 3 subsequent days (90 mg total).
Intervention: GSK4024484C
30 mg MAD Group
Participants receive a single dose of 30 mg per day of GSK4024484 or matching placebo during 3 subsequent days (90 mg total).
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of participants reporting serious adverse events (SAEs) after single ascending doses
Time Frame: From the signing of the informed consent (Day -2) until the follow up contact (Day 38 +/- 3 days post dose)
An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or an abnormal partner pregnancy outcome.
Percentage of participants reporting SAEs by severity after single ascending doses
Time Frame: From the signing of the informed consent (Day -2) until the follow up contact (Day 38 +/- 3 days post dose)
Mild SAE = a type of adverse event (AE) that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate SAE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe SAE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.
Percentage of participants reporting SAEs by severity after multiple ascending doses
Time Frame: From the signing of the informed consent (Day -2) until the follow up contact (Day 40 +/- 3 days post dose)
Mild SAE = a type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate SAE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe SAE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.
Percentage of participants reporting SAEs after multiple ascending doses
Time Frame: From the signing of the informed consent (Day -2) until the follow up contact (Day 40 +/- 3 days post dose)
An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or an abnormal partner pregnancy outcome.
Percentage of participants reporting non-serious AEs after single ascending doses
Time Frame: From study dose administration (Day 1) until the follow up contact (Day 38 +/- 3 days post dose)
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.
Percentage of participants reporting non-serious AEs by severity after single ascending doses
Time Frame: From study dose administration (Day 1) until the follow up contact (Day 38 +/- 3 days post dose)
Mild AE = a type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate AE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe AE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.
Percentage of participants reporting non-serious AEs after multiple ascending doses
Time Frame: From first study dose administration (Day 1) until the follow up contact (Day 40 +/- 3 days post dose)
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.
Percentage of participants reporting non-serious AEs by severity after multiple ascending doses
Time Frame: From first study dose administration (Day 1) until the follow up contact (Day 40 +/- 3 days post dose)
Mild AE = a type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate AE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe AE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.
Secondary Outcomes
- Part A: Area under the plasma drug concentration versus time curve from time zero (pre-dose) to last time of quantifiable concentration [AUC(0-t)] of GSK4024484C following single ascending doses in fasting conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part A: Area under the plasma drug concentration versus time curve from zero (pre-dose) extrapolated to infinite time [AUC(0-∞)] of GSK4024484C following single ascending doses in fasting conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part A: Maximum observed plasma drug concentration (Cmax) of GSK4024484C following single ascending doses in fasting conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part B: AUC(0-t) of GSK4024484C following multiple ascending doses in fasting conditions(From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose))
- Part B: Cmax of GSK4024484C following multiple ascending doses in fasting conditions(From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose))
- Part B: Tmax of GSK4024484C following multiple ascending doses in fasting conditions(From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose))
- Part B: t1/2 of GSK4024484C following multiple ascending doses in fasting conditions(From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose))
- Part A: AUC(0-∞) of GSK4024484C following single ascending doses in fed conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part A: Cmax of GSK4024484C following single ascending doses in fed conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK4024484C following single ascending doses in fasting conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part A: Apparent terminal half-life (t1/2) of GSK4024484C following single ascending doses in fasting conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part B: AUC(0-∞) of GSK4024484C following multiple ascending doses in fasting conditions(From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose))
- Part B: Area under the plasma drug concentration versus time curve from zero to time of trough plasma concentration [AUC(0-tau)] of GSK4024484C following multiple ascending doses in fasting conditions(Part B: From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose))
- Part B: Trough plasma concentration (Ctau) of GSK4024484C following multiple ascending doses in fasting conditions(From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose))
- Part A: AUC(0-t) of GSK4024484C following single ascending doses in fed conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part A: Tmax of GSK4024484C following single ascending doses in fed conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part B: Observed accumulation ratio (R) of GSK4024484 based on Cmax(RCmax) following multiple ascending doses(At Day 1 and at Day 3)
- Part A: t1/2 of GSK4024484C following single ascending doses in fed conditions(From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose))
- Part B: Observed accumulation ratio (R) of GSK4024484 based on AUC(Ro) following multiple ascending doses(At Day 1 and at Day 3)