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

NCT05044325 | Terminated Phase 1 Results

• 1 other identifier: 213376
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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

Keywords

First Time in Human; GSK3884464; Pharmacokinetics; Pharmacodynamics; Safety; Tolerability

Outcome Measures

Primary Outcomes (30)

• 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 Outcomes (2)

• 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

• 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

Study Arms (10)

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

EXPERIMENTAL

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; Drug: Placebo

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

EXPERIMENTAL

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; Drug: Placebo

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

EXPERIMENTAL

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; Drug: Placebo

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

EXPERIMENTAL

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; Drug: Placebo

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

EXPERIMENTAL

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; Drug: Placebo

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

EXPERIMENTAL

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; Drug: Placebo

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

EXPERIMENTAL

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; Drug: Placebo

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

EXPERIMENTAL

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; Drug: Placebo

Part 2 Cohort 4 (C4): GSK3884464 15 mg

EXPERIMENTAL

Participants received GSK3884464 15 mg through oral administration.

Drug: GSK3884464

Part 2 Cohort 4: Placebo C4

EXPERIMENTAL

Participants received placebo through oral administration in Cohort 4.

Drug: Placebo

Interventions

GSK3884464 DRUG

GSK3884464 will be administered

Part 1 Cohort 1 (C1): Placebo C1/ GSK3884464 3 milligrams (mg)/ GSK3884464 9mg; Part 1 Cohort 1: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1; Part 1 Cohort 1: GSK3884464 1 mg/ Placebo C1/ GSK3884464 9mg; Part 1 Cohort 2 (C2): Placebo C2/ GSK3884464 110 mg/ SD6; Part 1 Cohort 2: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2; Part 1 Cohort 2: GSK3884464 30 mg/ Placebo C2/ SD6; Part 1 Cohort 3 (C3): Placebo C3/ SD8/ SD9; Part 1 Cohort 3: GSK3884464 70 mg/ SD8/ Placebo C3; Part 2 Cohort 4 (C4): GSK3884464 15 mg

Placebo DRUG

Placebo to match GSK3884464 will be administered.

Part 1 Cohort 1 (C1): Placebo C1/ GSK3884464 3 milligrams (mg)/ GSK3884464 9mg; Part 1 Cohort 1: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1; Part 1 Cohort 1: GSK3884464 1 mg/ Placebo C1/ GSK3884464 9mg; Part 1 Cohort 2 (C2): Placebo C2/ GSK3884464 110 mg/ SD6; Part 1 Cohort 2: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2; Part 1 Cohort 2: GSK3884464 30 mg/ Placebo C2/ SD6; Part 1 Cohort 3 (C3): Placebo C3/ SD8/ SD9; Part 1 Cohort 3: GSK3884464 70 mg/ SD8/ Placebo C3; Part 2 Cohort 4: Placebo C4

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2021
• First Posted: September 14, 2021
• Study Start: September 20, 2021
• Primary Completion: August 5, 2022
• Study Completion: August 5, 2022
• Last Updated: May 2, 2024
• Results First Posted: May 2, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

GB (1)