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

November 3, 2023 updated by: GlaxoSmithKline

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

This will be a FTIH study which aims to evaluate safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and repeat oral doses of GSK3884464 administered to healthy participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion criteria:

  • Healthy as determined by the experienced investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring/assessment.
  • Part 1: Body weight greater than or equal to (>=)50 kilograms (kg), body mass index (BMI) >=18 and less than or equal to (<=)30 kilograms per square meter (kg/m^2) (inclusive). Part 2: Body weight >=50 kg, BMI >=22 and <=30 kg/m^2 (inclusive).
  • Participants with 18 to 50 years of age inclusive at the time of signing the informed consent.
  • Male or females of non-childbearing potential.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

Exclusion criteria:

  • History or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal (Gastroesophageal reflux disease [GERD], nausea, vomiting or dysphagia), endocrine, hematological or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
  • History of current or past significant renal diseases.
  • Clinically significant high blood pressure and/or history of hypertension as determined by the investigator.
  • Serum troponin I or troponin-T greater than (>) the upper limit of normal (ULN).
  • Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
  • Breast cancer within the past 10 years.
  • Any clinically relevant abnormality on the screening medical assessments.
  • Alanine transaminase (ALT) > ULN.
  • Bilirubin > ULN.
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Unable to refrain from the use of prescription or non-prescription drug including vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer [ for example (e.g.) Rifampin, St John's Wort extract]) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. By exception, all participants may take Paracetamol (<=2 grams/day) up to 48 hours prior to the first dose of study drug.
  • A positive laboratory confirmation of Coronavirus Disease-2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.
  • Participants with Glycated hemoglobin (HbA1c) greater than (>)48 millimoles per mol (mmol/mol) at screening.
  • Presence of Hepatitis B surface antigen at screening.
  • Positive Hepatitis C antibody test result at screening.
  • Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
  • Positive pre-study drug/alcohol screen.
  • Positive Human immunodeficiency virus (HIV) antibody test.
  • Screening urine albumin to creatinine ratio >=30 milligrams/grams (mg/gm) (>=3 mg/mmol).
  • Regular use of known drugs of abuse.
  • Regular alcohol consumption within six months prior to the study defined as: An average weekly intake of >=14 units for males >=14 units for females. One unit is equivalent to 8 gm of alcohol: a half-pint (approximately 240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Smokelyzer test levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g.nicotine patches or vaporizing devices) within 3 months prior to screening.
  • Participants with a history or current evidence of depression, bipolar disorder, suicidal ideation and behavior, or a lifetime history of suicide attempt will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1 Cohort 1 (C1): Placebo C1/ GSK3884464 3 milligrams (mg)/ GSK3884464 9mg
Participants received GSK3884464 or placebo through oral administration in the treatment sequence: Placebo C1/ GSK3884464 3 milligrams (mg)/ GSK3884464 9mg across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.
Drug: GSK3884464
GSK3884464 will be administered
Drug: Placebo
Placebo to match GSK3884464 will be administered.
Experimental: Part 1 Cohort 1: GSK3884464 1 mg/ Placebo C1/ GSK3884464 9mg
Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 1 mg/ Placebo C1/ GSK3884464 9mg across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.
Drug: GSK3884464
GSK3884464 will be administered
Drug: Placebo
Placebo to match GSK3884464 will be administered.
Experimental: Part 1 Cohort 1: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1
Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 1 mg/ GSK3884464 3 mg / Placebo C1 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.
Drug: GSK3884464
GSK3884464 will be administered
Drug: Placebo
Placebo to match GSK3884464 will be administered.
Experimental: Part 1 Cohort 2 (C2): Placebo C2/ GSK3884464 110 mg/ SD6
Participants received GSK3884464 or placebo through oral administration in the treatment sequence: Placebo C2/ GSK3884464 110 mg/ Single Dose (SD) 6 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.
Drug: GSK3884464
GSK3884464 will be administered
Drug: Placebo
Placebo to match GSK3884464 will be administered.
Experimental: Part 1 Cohort 2: GSK3884464 30 mg/ Placebo C2/ SD6
Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 30 mg/ Placebo C2/ SD6 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.
Drug: GSK3884464
GSK3884464 will be administered
Drug: Placebo
Placebo to match GSK3884464 will be administered.
Experimental: Part 1 Cohort 2: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2
Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 30 mg/ GSK3884464 110 mg / Placebo C2 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.
Drug: GSK3884464
GSK3884464 will be administered
Drug: Placebo
Placebo to match GSK3884464 will be administered.
Experimental: Part 1 Cohort 3 (C3): Placebo C3/ SD8/ SD9
Participants received GSK3884464 or placebo through oral administration in the treatment sequence: Placebo C3/ SD8/ SD9 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.
Drug: GSK3884464
GSK3884464 will be administered
Drug: Placebo
Placebo to match GSK3884464 will be administered.
Experimental: Part 1 Cohort 3: GSK3884464 70 mg/ SD8/ Placebo C3
Participants received GSK3884464 or placebo through oral administration in the treatment sequence: GSK3884464 70 mg/ SD8/ Placebo C3 across 3 treatment periods. There was a minimum of 7 days washout period between dosing in each session.
Drug: GSK3884464
GSK3884464 will be administered
Drug: Placebo
Placebo to match GSK3884464 will be administered.
Experimental: Part 2 Cohort 4 (C4): GSK3884464 15 mg
Participants received GSK3884464 15 mg through oral administration.
Drug: GSK3884464
GSK3884464 will be administered
Experimental: Part 2 Cohort 4: Placebo C4
Participants received placebo through oral administration in Cohort 4.
Drug: Placebo
Placebo to match GSK3884464 will be administered.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Up to Day 17
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.
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
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 (%).
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
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%.
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
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.
Up to Week 10
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.
Up to Week 10
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.
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
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%.
Up to Week 10
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.
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
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 (%)
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
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%.
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
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.
Upto Week 9
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.
Upto Week 9
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.
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
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%.
Upto Week 9
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.
Upto Week 9
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.
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
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].
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
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].
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 1: Change From Baseline in NAD(P)H Dehydrogenase Quinone 1 (NQO1) Messenger Ribonucleic Acid (mRNA) in Whole Blood Post Treatment With GSK3884464
Time Frame: Day1: pre-dose,30 minutes,1,1.5,2,3,4,6, 8,12,18,24 hours post-dose
Blood samples were collected at indicated time points for pharmacodynamic analysis of NQO1 mRNA.
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
Blood samples were collected at indicated time points for pharmacodynamic analysis of NQO1 mRNA for repeat dose administration. NA indicates standard deviation could not be calculated for single participant.
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 20, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 5, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 5, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 6, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 6, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 14, 2021

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 2, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 3, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 213376

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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