A First Time in Human (FTIH) Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Doses of GSK3884464 in Healthy Participants

GlaxoSmithKline (GSK)

Status and phase

Terminated

Phase 1

Conditions

Heart Failure

Treatments

Drug: Placebo

Drug: GSK3884464

Study type

Interventional

Funder types

Industry

Identifiers

NCT05044325

213376

Details and patient eligibility

About

This will be a FTIH study which aims to evaluate safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and repeat oral doses of GSK3884464 administered to healthy participants.

Enrollment

27 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy as determined by the experienced investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring/assessment.
Part 1: Body weight greater than or equal to (>=)50 kilograms (kg), body mass index (BMI) >=18 and less than or equal to (<=)30 kilograms per square meter (kg/m^2) (inclusive). Part 2: Body weight >=50 kg, BMI >=22 and <=30 kg/m^2 (inclusive).
Participants with 18 to 50 years of age inclusive at the time of signing the informed consent.
Male or females of non-childbearing potential.
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

Exclusion criteria

History or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal (Gastroesophageal reflux disease [GERD], nausea, vomiting or dysphagia), 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.
History of current or past significant renal diseases.
Clinically significant high blood pressure and/or history of hypertension as determined by the investigator.
Serum troponin I or troponin-T greater than (>) the upper limit of normal (ULN).
Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Breast cancer within the past 10 years.
Any clinically relevant abnormality on the screening medical assessments.
Alanine transaminase (ALT) > ULN.
Bilirubin > ULN.
Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Unable to refrain from the use of prescription or non-prescription drug including vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer [ for example (e.g.) Rifampin, St John's Wort extract]) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. By exception, all participants may take Paracetamol (<=2 grams/day) up to 48 hours prior to the first dose of study drug.
A positive laboratory confirmation of Coronavirus Disease-2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.
Participants with Glycated hemoglobin (HbA1c) greater than (>)48 millimoles per mol (mmol/mol) at screening.
Presence of Hepatitis B surface antigen at screening.
Positive Hepatitis C antibody test result at screening.
Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
Positive pre-study drug/alcohol screen.
Positive Human immunodeficiency virus (HIV) antibody test.
Screening urine albumin to creatinine ratio >=30 milligrams/grams (mg/gm) (>=3 mg/mmol).
Regular use of known drugs of abuse.
Regular alcohol consumption within six months prior to the study defined as: An average weekly intake of >=14 units for males >=14 units for females. One unit is equivalent to 8 gm of alcohol: a half-pint (approximately 240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Smokelyzer test levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g.nicotine patches or vaporizing devices) within 3 months prior to screening.
Participants with a history or current evidence of depression, bipolar disorder, suicidal ideation and behavior, or a lifetime history of suicide attempt will be excluded.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Double Blind

27 participants in 10 patient groups

Part 1 Cohort 1 (C1): Placebo C1/ GSK3884464 3 milligrams (mg)/ GSK3884464 9mg

Experimental group

Description:

Participants received GSK3884464 or placebo through oral administration in the treatment sequence: Placebo C1/ GSK3884464 3 milligrams (mg)/ GSK3884464 9mg across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.

Treatment:

Drug: GSK3884464

Drug: Placebo

Part 1 Cohort 1: GSK3884464 1 mg/ Placebo C1/ GSK3884464 9mg

Experimental group

Description:

Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 1 mg/ Placebo C1/ GSK3884464 9mg across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.

Treatment:

Drug: GSK3884464

Drug: Placebo

Part 1 Cohort 1: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1

Experimental group

Description:

Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.

Treatment:

Drug: GSK3884464

Drug: Placebo

Part 1 Cohort 2 (C2): Placebo C2/ GSK3884464 110 mg/ SD6

Experimental group

Description:

Participants received GSK3884464 or placebo through oral administration in the treatment sequence: Placebo C2/ GSK3884464 110 mg/ Single Dose (SD) 6 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.

Treatment:

Drug: GSK3884464

Drug: Placebo

Part 1 Cohort 2: GSK3884464 30 mg/ Placebo C2/ SD6

Experimental group

Description:

Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 30 mg/ Placebo C2/ SD6 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.

Treatment:

Drug: GSK3884464

Drug: Placebo

Part 1 Cohort 2: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2

Experimental group

Description:

Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.

Treatment:

Drug: GSK3884464

Drug: Placebo

Part 1 Cohort 3 (C3): Placebo C3/ SD8/ SD9

Experimental group

Description:

Participants received GSK3884464 or placebo through oral administration in the treatment sequence: Placebo C3/ SD8/ SD9 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.

Treatment:

Drug: GSK3884464

Drug: Placebo

Part 1 Cohort 3: GSK3884464 70 mg/ SD8/ Placebo C3

Experimental group

Description:

Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 70 mg/ SD8/ Placebo C3 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.

Treatment:

Drug: GSK3884464

Drug: Placebo

Part 2 Cohort 4 (C4): GSK3884464 15 mg

Experimental group

Description:

Participants received GSK3884464 15 mg through oral administration.

Treatment:

Drug: GSK3884464

Part 2 Cohort 4: Placebo C4

Experimental group

Description: