Last updated: 07/17/2024 17:56:10

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

GSK study ID
213376
See study documents
Clinicaltrials.gov ID
NCT05044325
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Parts 1: Number of participants with adverse events (AEs)

Timeframe: Up to Day 17

Parts 2: Number of participants with adverse events (AEs)

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: Up to Week 10

Part 1: Number of participants with clinically significant changes in Hepatobiliary laboratory values

Timeframe: Up to Week 10

Part 1: Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) laboratory values

Timeframe: 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

Timeframe: Up to Week 10

Part 1: Number of participants with clinically significant changes in continuous telemetry

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: Upto Week 9

Part 2: Cohorts 4: Number of participants with clinically significant changes in Hepatobiliary laboratory values

Timeframe: Upto Week 9

Part 2: Cohorts 4: Number of participants with clinically significant changes in 12-lead ECG laboratory values

Timeframe: 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

Timeframe: Upto Week 9

Part 2: Cohorts 4: Number of participants with clinically significant changes in echocardiogram

Timeframe: Upto Week 9

Part 2: Cohorts 4: Number of participants with clinically significant changes in continuous telemetry

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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

Timeframe: 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:

Part 1: Change from Baseline in NAD(P)H dehydrogenase Quinone 1 (NQO1) messenger Ribonucleic acid (mRNA) in whole blood post treatment with GSK3884464

Timeframe: 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

Timeframe: 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

Interventions:
  • Drug: GSK3884464
  • Drug: Placebo
    • Enrollment:
    27
    Primary completion date:
    2022-05-08
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Heart Failure
    Product
    Not applicable
    Collaborators
    Not applicable
    Study date(s)
    September 2021 to August 2022
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 50 Years
    Accepts healthy volunteers
    Yes
    • 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.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • 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.

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    Cambridge, United Kingdom, CB2 2GG
    Status
    Study Complete
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    Study documents

    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Other
    Actual primary completion date
    2022-05-08
    Actual study completion date
    2022-05-08

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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