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 Phase 1 study testing GSK3884464 in people with Heart Failure, run by GlaxoSmithKline at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Heart Failure
What is being tested?: GSK3884464
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 27 participants
Where: 1 siteUnited Kingdom
Study dates: 20 Sep 2021to 5 Aug 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

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Any clinically relevant abnormality on the screening medical assessments.
Alanine transaminase (ALT) > ULN.
Bilirubin > ULN.
Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Unable to refrain from the use of prescription or non-prescription drug including vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer [ for example (e.g.) Rifampin, St John's Wort extract]) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. By exception, all participants may take Paracetamol (<=2 grams/day) up to 48 hours prior to the first dose of study drug.
A positive laboratory confirmation of Coronavirus Disease-2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.
Participants with Glycated hemoglobin (HbA1c) greater than (>)48 millimoles per mol (mmol/mol) at screening.
Presence of Hepatitis B surface antigen at screening.
Positive Hepatitis C antibody test result at screening.
Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
Positive pre-study drug/alcohol screen.
Positive Human immunodeficiency virus (HIV) antibody test.
Screening urine albumin to creatinine ratio >=30 milligrams/grams (mg/gm) (>=3 mg/mmol).
Regular use of known drugs of abuse.
Regular alcohol consumption within six months prior to the study defined as: An average weekly intake of >=14 units for males >=14 units for females. One unit is equivalent to 8 gm of alcohol: a half-pint (approximately 240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Smokelyzer test levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g.nicotine patches or vaporizing devices) within 3 months prior to screening.
Participants with a history or current evidence of depression, bipolar disorder, suicidal ideation and behavior, or a lifetime history of suicide attempt will be excluded.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: 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

Conditions: Heart Failure
Being tested: GSK3884464, Placebo
Keywords: First Time in Human, GSK3884464, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability
Medical subject headings: Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK3884464Drug
GSK3884464 will be administered
PlaceboDrug
Placebo to match GSK3884464 will be administered.

Study groups in NCT05044325
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: GSK3884464; Drug: Placebo
Part 2 Cohort 4 (C4): GSK3884464 15 mg	Experimental	Participants received GSK3884464 15 mg through oral administration. Receives: Drug: GSK3884464
Part 2 Cohort 4: Placebo C4	Experimental	Participants received placebo through oral administration in Cohort 4. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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 (%).
Measured: 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%.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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%.
Measured: 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.
Measured: 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 (%)
Measured: 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%.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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%.
Measured: 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.
Measured: 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.
Measured: 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].
Measured: 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].
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Blood samples were collected at indicated time points for pharmacodynamic analysis of NQO1 mRNA.
Measured: 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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Sep 20215 Aug 2022

First posted14 Sep 2021
Study start20 Sep 2021
Primary completion5 Aug 2022
Study completion5 Aug 2022

Why it stopped: To allow for additional assessments from supplementary non-clinical activities.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Heart FailureStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05044325
Sponsor's protocol ID: 213376
Status last verified: Nov 2023
First submitted: 6 Sep 2021
Last updated: 2 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Heart Failure and Preserved Ejection Fraction, Heart Failure New York Heart Association Class III
Enrolling by invitation
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Study at a glance

From the registry record, last updated by the sponsor on 2 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT05044325
Acronym / sponsor ID: 213376
Conditions: Heart Failure
Keywords: First Time in Human, GSK3884464, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: To allow for additional assessments from supplementary non-clinical activities.
Enrolment: 27 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 20 Sep 2021 (actual)
Primary completion: 5 Aug 2022 (actual)
Study completion: 5 Aug 2022 (actual)
First posted: 14 Sep 2021 (actual)
Results: Posted 2 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 10

Arm	Type	Receives
Part 1 Cohort 1 (C1): Placebo C1/ GSK3884464 3 milligrams (mg)/ GSK3884464 9mg	Experimental	Drug: GSK3884464, Drug: PlaceboParticipants 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	Experimental	Drug: GSK3884464, Drug: PlaceboParticipants 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 1: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1	Experimental	Drug: GSK3884464, Drug: PlaceboParticipants 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	Experimental	Drug: GSK3884464, Drug: PlaceboParticipants 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	Experimental	Drug: GSK3884464, Drug: PlaceboParticipants 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 2: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2	Experimental	Drug: GSK3884464, Drug: PlaceboParticipants 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	Experimental	Drug: GSK3884464, Drug: PlaceboParticipants 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 3: GSK3884464 70 mg/ SD8/ Placebo C3	Experimental	Drug: GSK3884464, Drug: PlaceboParticipants 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 2 Cohort 4 (C4): GSK3884464 15 mg	Experimental	Drug: GSK3884464Participants received GSK3884464 15 mg through oral administration.
Part 2 Cohort 4: Placebo C4	Experimental	Drug: PlaceboParticipants received placebo through oral administration in Cohort 4.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (23 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK3884464GSK3884464 will be administered	Drug	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
PlaceboPlacebo to match GSK3884464 will be administered.	Drug	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

Primary outcome

Parts 1: Number of Participants With Adverse Events (AEs)
Time frame: 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.
Parts 2: Number of Participants With Adverse Events (AEs)
Time frame: 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.
Part 1: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: 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 1: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: 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
Time frame: 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 1: Number of Participants With Clinically Significant Changes in Hepatobiliary Laboratory Values
Time frame: 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
Time frame: 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.
Part 1: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: 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
Time frame: 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 Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: 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: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: 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 2: Cohorts 4: Number of Participants With Worst Case Urinalysis Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: 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 Hepatobiliary Laboratory Values
Time frame: 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 Clinically Significant Changes in 12-lead ECG Laboratory Values
Time frame: 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: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3884464 Following Single Dose Administration
Time frame: 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 1: Terminal Half-life (T1/2) of GSK3884464 Following Single Dose Administration
Time frame: 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: AUC Over the Dosing Interval (AUC[Tau]) of GSK3884464 Following Repeat Dose Administration
Time frame: 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: Cmax of GSK3884464 Following Repeat Dose Administration
Time frame: 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
Time frame: 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: Tmax of GSK3884464 Following Repeat Dose Administration
Time frame: 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 2: Cohorts 4: T1/2 of GSK3884464 Following Repeat Dose Administration
Time frame: 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 2: Cohorts 4: Accumulation Ratio Based on AUC(Tau) (RAUC) of GSK3884464 Following Repeat Dose Administration
Time frame: 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 Cmax (RCmax) of GSK3884464 Following Repeat Dose Administration
Time frame: 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: Accumulation Ratio Based on Ctau (RCtau) of GSK3884464 Following Repeat Dose Administration
Time frame: 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.

2 secondary outcomes

Part 1: Change From Baseline in NAD(P)H Dehydrogenase Quinone 1 (NQO1) Messenger Ribonucleic Acid (mRNA) in Whole Blood Post Treatment With GSK3884464
Time frame: 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
Time frame: 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

Results and safety

Results posted to the registry on 2 May 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1 Cohort 1 (C1): Placebo C1/ GSK3884464 3 Milligrams (mg)/ GSK3884464 9mg	3	3
Part 1 Cohort 1: GSK3884464 1 mg/ Placebo C1/ GSK3884464 9mg	3	3
Part 1 Cohort 1: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1	3	2
Part 1 Cohort 2 (C2): Placebo C2/ GSK3884464 110 mg/ SD6	3	1
Part 1 Cohort 2: GSK3884464 30 mg/ Placebo C2/ SD6	3	1
Part 1 Cohort 2: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2	3	0
Part 1 Cohort 3 (C3): Placebo C3/ SD8/ SD9	1	0
Part 1 Cohort 3: GSK3884464 70 mg/ SD8/ Placebo C3	1	0
Part 2 Cohort 4 (C4): GSK3884464 15 mg	0	0
Part 2 Cohort 4: Placebo C4	0	0

Primary outcome: Parts 1: Number of Participants With Adverse Events (AEs)

Time frame: Up to Day 17. Count of participants. Unit: Participants

Measure	Part 1 Cohort 1: Placebo C1 n = 9	Part 1 Cohort 1: GSK3884464 1 mg n = 6	Part 1 Cohort 1: GSK3884464 3 mg n = 6	Part 1 Cohort 1: GSK3884464 9 mg n = 6	Part 1 Cohort 2: Placebo C2 n = 5	Part 1 Cohort 2: GSK3884464 30 mg n = 6	Part 1 Cohort 2: GSK3884464 110 mg n = 3	Part 1 Cohort 3: Placebo C3 n = 1	Part 1 Cohort 3: GSK3884464 70 mg n = 1
Value	2	1	0	3	3	1	3	1	1

Population analysed: The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study intervention.

Primary outcome: Parts 2: Number of Participants With Adverse Events (AEs)

Time frame: Up to Day 29. Count of participants. Unit: Participants

Measure	Part 2 Cohort 4: Placebo C4 n = 1	Part 2 Cohort 4: GSK3884464 15 mg n = 1
Value	1	1

Population analysed: The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study intervention.

Primary outcome: Part 1: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

Time frame: Up to Week 10. Count of participants. Unit: Participants

Measure	Part 1 Cohort 1: Placebo C1 n = 3	Part 1 Cohort 1: GSK3884464 1 mg n = 6	Part 1 Cohort 1: GSK3884464 3 mg n = 6	Part 1 Cohort 1: GSK3884464 9 mg n = 6	Part 1 Cohort 2: Placebo C2 n = 5	Part 1 Cohort 2: GSK3884464 30 mg n = 6	Part 1 Cohort 2: GSK3884464 110 mg n = 3	Part 1 Cohort 3: Placebo C3 n = 1	Part 1 Cohort 3: GSK3884464 70 mg n = 1
ALT, Period 1 Worst Case Post-Baseline, To Low	0	0	–	–	0	0	–	0	0
ALT, Period 1 Worst Case Post-Baseline, To W/in Range or No Change	3	6	–	–	3	6	–	1	0
ALT, Period 1 Worst Case Post-Baseline, To High	0	0	–	–	0	0	–	0	1
ALT, Period 2 Worst Case Post-Baseline, To Low	0	–	0	–	0	–	0	–	–
ALT, Period 2 Worst Case Post-Baseline, To W/in Range or No Change	3	–	6	–	2	–	1	–	–
ALT, Period 2 Worst Case Post-Baseline, To High	0	–	0	–	0	–	2	–	–
ALT, Period 3 Worst Case Post-Baseline, To Low	0	–	–	0	–	–	–	–	–
ALT, Period 3 Worst Case Post-Baseline, To W/in Range or No Change

Primary outcome: Part 1: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

Time frame: Up to Week 10. Count of participants. Unit: Participants

Measure	Part 1 Cohort 1: Placebo C1 n = 3	Part 1 Cohort 1: GSK3884464 1 mg n = 6	Part 1 Cohort 1: GSK3884464 3 mg n = 6	Part 1 Cohort 1: GSK3884464 9 mg n = 6	Part 1 Cohort 2: Placebo C2 n = 5	Part 1 Cohort 2: GSK3884464 30 mg n = 6	Part 1 Cohort 2: GSK3884464 110 mg n = 3	Part 1 Cohort 3: Placebo C3 n = 1	Part 1 Cohort 3: GSK3884464 70 mg n = 1
Erythrocytes, Period 1 Worst Case Post-Baseline, To Low	0	0	–	–	0	0	–	0	0
Erythrocytes, Period 1 Worst Case Post-Baseline, To W/in Range or No Change	3	6	–	–	3	6	–	1	1
Erythrocytes, Period 1 Worst Case Post-Baseline, To High	0	0	–	–	0	0	–	0	0
Erythrocytes, Period 2 Worst Case Post-Baseline, To Low	0	–	0	–	0	–	0	–	–
Erythrocytes, Period 2 Worst Case Post-Baseline, To W/in Range or No Change	3	–	6	–	2	–	3	–	–
Erythrocytes, Period 2 Worst Case Post-Baseline, To High	0	–	0	–	0	–	0	–	–
Erythrocytes, Period 3 Worst Case Post-Baseline, To Low	0	–	–	0	–	–	–	–	–
Erythrocytes, Period 3 Worst Case Post-Baseline, To W/in Range or No Change

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: All AEs and SAEs were collected up to Day 17 for Cohort 1, 2 and 3 of Part 1, up to Day 29 for Cohort 4 of Part 2.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 Cohort 1: Placebo C1	0 of 9 (0%)	2 of 9 (22.2%)	0 of 9
Part 1 Cohort 1: GSK3884464 1 mg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1 Cohort 1: GSK3884464 3 mg	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Part 1 Cohort 1: GSK3884464 9 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 1 Cohort 2: Placebo C2	1 of 5 (20%)	3 of 5 (60%)	0 of 5
Part 1 Cohort 2: GSK3884464 30 mg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1 Cohort 2: GSK3884464 110 mg	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Part 1 Cohort 3: Placebo C3	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Part 1 Cohort 3: GSK3884464 70 mg	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Part 2 Cohort 4: Placebo C4	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Part 2 Cohort 4: GSK3884464 15 mg	0 of 1 (0%)	1 of 1 (100%)	0 of 1

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK3884464 in people with Heart Failure, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Parts 1: Number of Participants With Adverse Events (AEs) (time frame: Up to Day 17). The study lists 30 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05044325.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2024.