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

NCT ID: NCT05044325

Last Updated: 2024-05-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-20
• Study Completion Date: 2022-08-05

Brief Summary

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

GSK3884464

Intervention Type: DRUG

GSK3884464 will be administered

Placebo

Intervention Type: DRUG

Placebo to match GSK3884464 will be administered.

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

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.

Group Type: EXPERIMENTAL

GSK3884464

Intervention Type: DRUG

GSK3884464 will be administered

Placebo

Intervention Type: DRUG

Placebo to match GSK3884464 will be administered.

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

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.

Group Type: EXPERIMENTAL

GSK3884464

Intervention Type: DRUG

GSK3884464 will be administered

Placebo

Intervention Type: DRUG

Placebo to match GSK3884464 will be administered.

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

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.

Group Type: EXPERIMENTAL

GSK3884464

Intervention Type: DRUG

GSK3884464 will be administered

Placebo

Intervention Type: DRUG

Placebo to match GSK3884464 will be administered.

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

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.

Group Type: EXPERIMENTAL

GSK3884464

Intervention Type: DRUG

GSK3884464 will be administered

Placebo

Intervention Type: DRUG

Placebo to match GSK3884464 will be administered.

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

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.

Group Type: EXPERIMENTAL

GSK3884464

Intervention Type: DRUG

GSK3884464 will be administered

Placebo

Intervention Type: DRUG

Placebo to match GSK3884464 will be administered.

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

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.

Group Type: EXPERIMENTAL

GSK3884464

Intervention Type: DRUG

GSK3884464 will be administered

Placebo

Intervention Type: DRUG

Placebo to match GSK3884464 will be administered.

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

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.

Group Type: EXPERIMENTAL

GSK3884464

Intervention Type: DRUG

GSK3884464 will be administered

Placebo

Intervention Type: DRUG

Placebo to match GSK3884464 will be administered.

Part 2 Cohort 4 (C4): GSK3884464 15 mg

Participants received GSK3884464 15 mg through oral administration.

Group Type: EXPERIMENTAL

GSK3884464

Intervention Type: DRUG

GSK3884464 will be administered

Part 2 Cohort 4: Placebo C4

Participants received placebo through oral administration in Cohort 4.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo to match GSK3884464 will be administered.

Interventions

GSK3884464

GSK3884464 will be administered

Intervention Type: DRUG

Placebo

Placebo to match GSK3884464 will be administered.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Cambridge, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

213376

Identifier Type: -

Identifier Source: org_study_id