A Study to Investigate the Safety of GSK4024484 in Healthy Adult Participants

GlaxoSmithKline (GSK)

Status and phase: Enrolling; Phase 1

Conditions: Malaria, Falciparum

Treatments: Drug: GSK4024484C; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06171113

218708

Details and patient eligibility

About

The primary purpose of the study is to characterise the safety of GSK4024484 in healthy participants within a controlled pharmacokinetic (PK) range.

Enrollment: 144 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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.

Exclusion criteria

1. 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.
2. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
3. 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.
4. QTcF (Fridericia's formula) >450 msec based on average of triplicate ECGs. The QTcF is the QT interval corrected for heart rate according to QTcF.
5. More than 100 ventricular ectopic complexes in 24 hrs by Holter screening or any other clinically significant Holter abnormalities determined by the investigator.
6. Presence or history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
7. Heart rate <40 or >100 beats per minute (bpm).
8. Evidence of previous myocardial infarction or any clinically significant conduction abnormality such as (including but not specific to left complete bundle branch block, AV block [2nd degree or higher], WPW syndrome). Long standing RBBB is permitted.
9. Past or intended use of over-the-counter or prescription medication, including herbal medications, CBD-based products, PPIs or 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 be considered on a case by case basis by the investigator in consultation with the medical monitor. Paracetamol is permitted (capped at ≤2 grams/day).
10. Participation in the study that would result in loss of blood or blood products in excess of 500 mL within a 56-day period.
11. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
12. Current enrolment or past participation (within the last 30 days before planned first dose in this study) in any other clinical study involving an investigational study intervention or any other type of medical research.
13. Participants previously dosed in this study.
14. Presence of HBsAg [or HBcAb] at screening or within 3 months prior to first dose of study intervention.
15. Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
16. Positive hepatitis C RNA (ribonucleic acid) test result at screening or within 3 months prior to first dose of study intervention.
17. Positive pre-study drug/alcohol screen.
18. Positive HIV antibody test.
19. Carbon monoxide levels indicative of smoking or more than 10 pack year history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
20. Use of known recreational drugs or drugs of abuse.
21. 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.
22. A positive confirmation of COVID-19 infection according to local procedures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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144 participants in 12 patient groups

6 mg single ascending dose (SAD) Group

Experimental group

Description:

Participants receive a 6 mg single dose of GSK4024484 or matching placebo, in a fasted state.

Treatment:

Drug: GSK4024484C

Drug: Placebo

12 mg SAD Group

Experimental group

Description:

Participants receive a 12 mg single dose of GSK4024484 or matching placebo, in a fasted state.

Treatment:

Drug: GSK4024484C

Drug: Placebo

24 mg SAD Group

Experimental group

Description:

Participants receive a 24 mg single dose of GSK4024484 or matching placebo, in a fasted state.

Treatment:

Drug: GSK4024484C

Drug: Placebo

40 mg SAD Group

Experimental group

Description:

Participants receive a 40 mg single dose of GSK4024484 or matching placebo, in a fasted state.

Treatment:

Drug: GSK4024484C

Drug: Placebo

60 mg SAD Group

Experimental group

Description:

Participants receive a 60 mg single dose of GSK4024484 or matching placebo, in a fasted state.

Treatment:

Drug: GSK4024484C

Drug: Placebo

80 mg SAD Group

Experimental group

Description:

Participants receive a 80 mg single dose of GSK4024484 or matching placebo, in a fasted state.

Treatment:

Drug: GSK4024484C

Drug: Placebo

Food Effect Group

Experimental group

Description:

Participants receive a single study dose of either GSK4024484 or matching placebo in a fed state.

Treatment:

Drug: GSK4024484C

Drug: Placebo

100 mg SAD Group

Experimental group

Description:

Participants receive a 100 mg single dose of GSK4024484 or matching placebo.

Treatment:

Drug: GSK4024484C

Drug: Placebo

Optional Group

Experimental group

Description:

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.

Treatment:

Drug: GSK4024484C

Drug: Placebo

10 mg multiple ascending doses (MAD) Group

Experimental group

Description:

Participants receive a single dose of 10 mg per day of GSK4024484 or matching placebo during 3 subsequent days (30 mg total).

Treatment:

Drug: GSK4024484C

Drug: Placebo

20 mg MAD Group

Experimental group

Description:

Participants receive a single dose of 20 mg per day of GSK4024484 or matching placebo during 3 subsequent days (60 mg total).

Treatment:

Drug: GSK4024484C

Drug: Placebo

30 mg MAD Group

Experimental group

Description:

Participants receive a single dose of 30 mg per day of GSK4024484 or matching placebo during 3 subsequent days (90 mg total).

Treatment:

Drug: GSK4024484C

Drug: Placebo