Malaria, Falciparum
Conditions
Keywords
First time in human, Safety, Pharmacokinetics, GSK4024484, Healthy adults, Food effect, Single oral doses, Multiple oral doses
Brief summary
The primary purpose of the study is to characterise the safety of GSK4024484 in healthy participants within a controlled pharmacokinetic (PK) range, and the effect of food on the study intervention.
Interventions
DRUGGSK4024484C
Doses administrated orally with 240 mL of water.
DRUGPlacebo
Doses administrated orally with 240 mL of water.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent. 2. Participants who are considered healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac assessment. 3. 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. 4. ALT (Alanine transaminase) and AST (Aspartate transaminase) within the normal range at screening. 5. Total bilirubin within the normal range unless the participant is known to have Gilbert's syndrome. 6. Body weight ≥50kg, and BMI within the range 19 to 32 kilogram per square metre (kg/m\^2) inclusive. 7. Male participants and female participants who are not of child bearing potential. 8. The participant is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants reporting serious adverse events (SAEs) after single ascending doses | 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 | 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 after multiple ascending doses | 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 SAEs by severity after multiple ascending doses | 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 non-serious AEs after single ascending doses | 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 | 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 | 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 | 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
| Measure | Time frame |
|---|---|
| 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 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-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: 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: 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 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: 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: 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 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 |
| Part B: Observed accumulation ratio (R) of GSK4024484 based on Cmax(RCmax) following multiple ascending doses | At Day 1 and at Day 3 |
Countries
United Kingdom
Outcome results
None listed