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

Phase 1

Terminated

Conditions: Heart Failure

Interventions: Drug: GSK3884464
Drug: Placebo

Registration Number: NCT05044325

Lead Sponsor: GlaxoSmithKline

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Part 1 Cohort 1: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1	GSK3884464	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.
Part 1 Cohort 2 (C2): Placebo C2/ GSK3884464 110 mg/ SD6	Placebo	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.
Part 1 Cohort 3: GSK3884464 70 mg/ SD8/ Placebo C3	Placebo	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.
Part 1 Cohort 1 (C1): Placebo C1/ GSK3884464 3 milligrams (mg)/ GSK3884464 9mg	Placebo	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.
Part 1 Cohort 1: GSK3884464 1 mg/ Placebo C1/ GSK3884464 9mg	Placebo	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.
Part 1 Cohort 3: GSK3884464 70 mg/ SD8/ Placebo C3	GSK3884464	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.
Part 1 Cohort 2: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2	Placebo	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.
Part 1 Cohort 3 (C3): Placebo C3/ SD8/ SD9	GSK3884464	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.
Part 1 Cohort 1: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1	Placebo	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.
Part 1 Cohort 2 (C2): Placebo C2/ GSK3884464 110 mg/ SD6	GSK3884464	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.
Part 1 Cohort 2: GSK3884464 30 mg/ Placebo C2/ SD6	Placebo	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.
Part 1 Cohort 3 (C3): Placebo C3/ SD8/ SD9	Placebo	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.
Part 2 Cohort 4 (C4): GSK3884464 15 mg	GSK3884464	Participants received GSK3884464 15 mg through oral administration.
Part 2 Cohort 4: Placebo C4	Placebo	Participants received placebo through oral administration in Cohort 4.
Part 1 Cohort 1 (C1): Placebo C1/ GSK3884464 3 milligrams (mg)/ GSK3884464 9mg	GSK3884464	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.
Part 1 Cohort 2: GSK3884464 30 mg/ Placebo C2/ SD6	GSK3884464	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.
Part 1 Cohort 1: GSK3884464 1 mg/ Placebo C1/ GSK3884464 9mg	GSK3884464	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.
Part 1 Cohort 2: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2	GSK3884464	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.

Primary Outcome Measures

Name	Time	Method
Part 1: Number of Participants With Clinically Significant Changes in Hepatobiliary Laboratory Values	Up to Week 10	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.
Part 1: Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Laboratory Values	Up to Week 10	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.
Parts 2: Number of Participants With Adverse Events (AEs)	Up to Day 29	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.
Parts 1: Number of Participants With Adverse Events (AEs)	Up to Day 17	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.
Part 1: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Up to Week 10	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 (%).
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in Hepatobiliary Laboratory Values	Upto Week 9	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.
Part 2: Cohorts 4: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Upto Week 9	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 (%)
Part 2: Cohorts 4: Tmax of GSK3884464 Following Repeat Dose Administration	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	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.
Part 1: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Up to Week 10	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%.
Part 1: Number of Participants With Worst Case Urinalysis Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Up to Week 10	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.
Part 2: Cohorts 4: Number of Participants With Worst Case Urinalysis Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Upto Week 9	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.
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in 12-lead ECG Laboratory Values	Upto Week 9	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.
Part 2: Cohorts 4: Cmax of GSK3884464 Following Repeat Dose Administration	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	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.
Part 2: Cohorts 4: Trough Plasma Concentration (Ctau) of GSK3884464 Following Repeat Dose Administration	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	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.
Part 2: Cohorts 4: T1/2 of GSK3884464 Following Repeat Dose Administration	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	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.
Part 1: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Up to Week 10	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%.
Part 1: Number of Participants With Clinically Significant Changes in Continuous Telemetry	Upto Day 3	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.
Part 2: Cohorts 4: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Upto Week 9	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%.
Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3884464 Following Single Dose Administration	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	Blood samples were collected at indicated time points for pharmacokinetic analysis of Tmax.
Part 2: Cohorts 4: AUC Over the Dosing Interval (AUC[Tau]) of GSK3884464 Following Repeat Dose Administration	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	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.
Part 2: Cohorts 4: Accumulation Ratio Based on Cmax (RCmax) of GSK3884464 Following Repeat Dose Administration	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	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.
Part 2: Cohorts 4: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Upto Week 9	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%.
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in Echocardiogram	Upto Week 9	Echocardiography was performed at screening and Part 2 of the study using sound waves.
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in Continuous Telemetry	Upto Day 14	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.
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	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	Blood samples were collected at indicated time points for pharmacokinetic analysis of AUC\[0-t\].
Part 1: AUC From Time Zero to Infinity (AUC[0-inf]) of GSK3884464 Following Single Dose Administration	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	Blood samples were collected at indicated time points for pharmacokinetic analysis of AUC\[0-t\].
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3884464 Following Single Dose Administration	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	Blood samples were collected at indicated time points for pharmacokinetic analysis of Cmax.
Part 1: Terminal Half-life (T1/2) of GSK3884464 Following Single Dose Administration	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	Blood samples were collected at indicated time points for pharmacokinetic analysis of T1/2.
Part 2: Cohorts 4: Accumulation Ratio Based on AUC(Tau) (RAUC) of GSK3884464 Following Repeat Dose Administration	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	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.
Part 2: Cohorts 4: Accumulation Ratio Based on Ctau (RCtau) of GSK3884464 Following Repeat Dose Administration	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	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.

Secondary Outcome Measures

Name	Time	Method
Part 1: Change From Baseline in NAD(P)H Dehydrogenase Quinone 1 (NQO1) Messenger Ribonucleic Acid (mRNA) in Whole Blood Post Treatment With GSK3884464	Day1: pre-dose,30 minutes,1,1.5,2,3,4,6, 8,12,18,24 hours post-dose	Blood samples were collected at indicated time points for pharmacodynamic analysis of NQO1 mRNA.
Part 2: Cohorts 4: Change From Baseline in NQO1 mRNA in Whole Blood Post Treatment With GSK3884464	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	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.