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

A Two-Part First Time in Human (FTIH) Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Oral Doses of GSK3884464 in a Randomized, Double Blind, Placebo-Controlled, Dose Escalation Study in Healthy Participants

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.

Study Overview

• Status: Terminated
• Conditions: Heart Failure
• Intervention / Treatment: Drug: GSK3884464; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 2GG
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: GSK3884464; GSK3884464 will be administered; Drug: Placebo; Placebo to match GSK3884464 will be administered.
Experimental: 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.	Drug: GSK3884464; GSK3884464 will be administered; Drug: Placebo; Placebo to match GSK3884464 will be administered.
Experimental: 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.	Drug: GSK3884464; GSK3884464 will be administered; Drug: Placebo; Placebo to match GSK3884464 will be administered.
Experimental: 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.	Drug: GSK3884464; GSK3884464 will be administered; Drug: Placebo; Placebo to match GSK3884464 will be administered.
Experimental: 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.	Drug: GSK3884464; GSK3884464 will be administered; Drug: Placebo; Placebo to match GSK3884464 will be administered.
Experimental: 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.	Drug: GSK3884464; GSK3884464 will be administered; Drug: Placebo; Placebo to match GSK3884464 will be administered.
Experimental: 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.	Drug: GSK3884464; GSK3884464 will be administered; Drug: Placebo; Placebo to match GSK3884464 will be administered.
Experimental: 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.	Drug: GSK3884464; GSK3884464 will be administered; Drug: Placebo; Placebo to match GSK3884464 will be administered.
Experimental: Part 2 Cohort 4 (C4): GSK3884464 15 mg; Participants received GSK3884464 15 mg through oral administration.	Drug: GSK3884464; GSK3884464 will be administered
Experimental: Part 2 Cohort 4: Placebo C4; Participants received placebo through oral administration in Cohort 4.	Drug: Placebo; Placebo to match GSK3884464 will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1: Number of Participants With Adverse Events (AEs)	An AE is defined as 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.	Up to Day 17
Parts 2: Number of Participants With Adverse Events (AEs)	An AE is defined as 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.	Up to Day 29
Part 1: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Blood samples were collected for analysis of chemistry parameters. PCI ranges were >2*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase [ALT]), >2*ULN (U/L) (Aspartate Aminotransferase ([AST]), >2*ULN (Alkaline Phosphatase [ALP]) (U/L), >1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >7.5 mmol/L (glucose), <3 or >5.3 mmol/L (potassium), <130 or >149 mmol/L (sodium). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).	Up to Week 10
Part 1: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Blood samples were collected for analysis of hematology parameters. The ranges for hematology parameters are as follows: Hematocrit[>51 percent(%)-male, >45%-female], Hemoglobin [Higher: >175 grams/Liter(g/L) in male, >150g/L in female and Low: less than(<) 100g/L in male, <95g/L in female], Lymphocytes[<0.97 10^9/L], Neutrophils[<1.5 10^9/L], Platelets[High: >550 10^9/ L and Low: <100 10^9/ L], White blood cells[High:>18 10^9/L Low:<2 10^9/L], Red blood cells[Low: <3.0 10^12/L in male, <2.5 10^12/L]. Participants were counted in worst case category that their value changes to (low, within range [W/in] or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example-High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' & 'To High', so the percentages may not add to 100%.	Up to Week 10
Part 1: Number of Participants With Worst Case Urinalysis Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Urine samples were collected to assess urine glucose, protein and ketones using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase.	Up to Week 10
Part 1: Number of Participants With Clinically Significant Changes in Hepatobiliary Laboratory Values	Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT)/combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) >= 5 and ALT >=3xULN.	Up to Week 10
Part 1: Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Laboratory Values	Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.	Up to Week 10
Part 1: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR), body temperature, respiratory rate (RR) and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (millimeters of mercury[mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.	Up to Week 10
Part 1: Number of Participants With Clinically Significant Changes in Continuous Telemetry	Continuous cardiac telemetry was performed in a supine position after at least 5 minutes of rest. Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented.	Upto Day 3
Part 2: Cohorts 4: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase [ALT]), >=2*ULN (U/L) (Aspartate Aminotransferase ([AST]), >=2*ULN (Alkaline Phosphatase [ALP]) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%)	Upto Week 9
Part 2: Cohorts 4: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Blood samples were collected for analysis of hematology parameters. The ranges for hematology parameters are as follows: Hematocrit[>51 % in male, >45% in female], Haemoglobin[Higher: > 175 grams/Litre (g/L) in male, >150 g/L in female and Low: less than (<) 100 g/L in male, <95 g/L in female], Lymphocytes[<0.97 10^9/L], Neutrophils[<1.5 10^9/L], Platelets[High: > 550 10^9/ L and Low: < 100 10^9/ L], White blood cells[High:>18 10^9/L Low:<2 10^9/L], Red blood cells[Low: <3.0 10^12/L in male, <2.5 10^12/L]. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' & 'To High', so the percentages may not add to 100%.	Upto Week 9
Part 2: Cohorts 4: Number of Participants With Worst Case Urinalysis Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Urine samples were collected to assess urine glucose, protein, occult blood and ketones using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase.	Upto Week 9
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in Hepatobiliary Laboratory Values	Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT) in combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) greater than or equal to (>=) 5 and ALT >=3xULN.	Upto Week 9
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in 12-lead ECG Laboratory Values	Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.	Upto Week 9
Part 2: Cohorts 4: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR), body temperature, respiratory rate (RR) and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (millimeters of mercury[mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.	Upto Week 9
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in Echocardiogram	Echocardiography was performed at screening and Part 2 of the study using sound waves.	Upto Week 9
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in Continuous Telemetry	Continuous cardiac telemetry was performed in a supine position after at least 5 minutes of rest. Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented.	Upto Day 14
Part 1: Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of GSK3884464 Following Single Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of AUC[0-t].	Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose
Part 1: AUC From Time Zero to Infinity (AUC[0-inf]) of GSK3884464 Following Single Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of AUC[0-t].	Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3884464 Following Single Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of Cmax.	Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose
Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3884464 Following Single Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of Tmax.	Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose
Part 1: Terminal Half-life (T1/2) of GSK3884464 Following Single Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of T1/2.	Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose
Part 2: Cohorts 4: AUC Over the Dosing Interval (AUC[Tau]) of GSK3884464 Following Repeat Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of AUC [tau] for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant.	Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose
Part 2: Cohorts 4: Cmax of GSK3884464 Following Repeat Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of Cmax for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant.	Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose
Part 2: Cohorts 4: Trough Plasma Concentration (Ctau) of GSK3884464 Following Repeat Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of Ctau for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant.	Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose
Part 2: Cohorts 4: Tmax of GSK3884464 Following Repeat Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of Tmax for repeat dose administration. NA indicates full range could not be calculated for single participant.	Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose
Part 2: Cohorts 4: T1/2 of GSK3884464 Following Repeat Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of T1/2 for repeat dose administration. NA indicates full range could not be calculated for single participant.	Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose
Part 2: Cohorts 4: Accumulation Ratio Based on AUC(Tau) (RAUC) of GSK3884464 Following Repeat Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of RAUC for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant.	Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose
Part 2: Cohorts 4: Accumulation Ratio Based on Cmax (RCmax) of GSK3884464 Following Repeat Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of RCmax for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant.	Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose
Part 2: Cohorts 4: Accumulation Ratio Based on Ctau (RCtau) of GSK3884464 Following Repeat Dose Administration	Blood samples were collected at indicated time points for pharmacokinetic analysis of RCtau for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant.	Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Change From Baseline in NAD(P)H Dehydrogenase Quinone 1 (NQO1) Messenger Ribonucleic Acid (mRNA) in Whole Blood Post Treatment With GSK3884464	Blood samples were collected at indicated time points for pharmacodynamic analysis of NQO1 mRNA.	Day1: pre-dose,30 minutes,1,1.5,2,3,4,6, 8,12,18,24 hours post-dose
Part 2: Cohorts 4: Change From Baseline in NQO1 mRNA in Whole Blood Post Treatment With GSK3884464	Blood samples were collected at indicated time points for pharmacodynamic analysis of NQO1 mRNA for repeat dose administration. NA indicates standard deviation could not be calculated for single participant.	Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Actual): August 5, 2022
• Study Completion (Actual): August 5, 2022

Study Registration Dates

• First Submitted: September 6, 2021
• First Submitted That Met QC Criteria: September 6, 2021
• First Posted (Actual): September 14, 2021

Study Record Updates

• Last Update Posted (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Tolerability; Pharmacodynamics; First Time in Human; GSK3884464
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 213376

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No