Last updated: 05/10/2022 19:00:08

Safety, tolerability and pharmacokinetic investigation of GSK3882347 in healthy participants.

GSK study ID
212148
See study documents
Clinicaltrials.gov ID
NCT04488770
See results summary
EudraCT ID
2020-000680-23
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Double-Blind Randomized, Placebo-Controlled, Single and Repeated Oral Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics (including food effect) of GSK3882347 in Healthy Participants
Trial description: This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, first time in human (FTIH) study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetics (PK) of GSK3882347 in healthy adult men and Woman of Non Childbearing Potential (WONCBP). Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each participant in the SAD cohort will receive a single dose of GSK3882347 or placebo (PBO) in 3:1 ratio and in Part 2 (MAD), participants will be randomized in a 4:1 ratio to receive active treatment and placebo. Part 1 will consist of two cohorts with a maximum of four-period for each cohort, the food effect evaluation will be conducted in last period (Period 4) in only one of the cohorts based on the observed human pharmacokinetics (PK). Part 2 will consist of maximum of four cohorts for each of the MAD dose or placebo.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)

Timeframe: Up to 3 months

Part 2: Number of Participants With Non-serious AEs and SAEs

Timeframe: Up to 26 days

Part 1: Number of participants with treatment related AEs

Timeframe: Up to 3 months

Part 2: Number of participants with treatment related AEs

Timeframe: Up to 26 days

Part 1: Number of participants with worst-case hematology results relative to Potential Clinical Importance (PCI) criteria post-Baseline relative to Baseline

Timeframe: Up to 3 months

Part 2: Number of participants with worst-case hematology results relative to PCI criteria post-Baseline relative to Baseline

Timeframe: Up to 26 days

Part 1: Number of participants with worst-case clinical chemistry results relative to PCI criteria post-Baseline relative to Baseline

Timeframe: Up to 3 months

Part 2: Number of participants with worst-case clinical chemistry results relative to PCI criteria post-Baseline relative to Baseline

Timeframe: Up to 26 days

Part 1: Number of participants with worst case urinalysis results Post Baseline relative to Baseline

Timeframe: Up to 3 months

Part 2: Number of participants with worst case urinalysis results Post Baseline relative to Baseline

Timeframe: Up to 26 days

Part 1: Number of participants with worst case vital signs results relative to PCI criteria post Baseline relative to Baseline

Timeframe: Up to 3 months

Part 2: Number of participants with worst case vital signs results relative to PCI criteria post Baseline relative to Baseline

Timeframe: Up to 26 days

Part 1: Number of participants with worst case abnormal Electrocardiogram (ECG) results post Baseline relative to Baseline

Timeframe: Up to 3 months

Part 2: Number of participants with worst case abnormal ECG results post Baseline relative to Baseline

Timeframe: Up to 26 days

Part 1: Area under the concentration-time curve from time zero to 24 hours (AUC[0-24]) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose in each treatment period

Part 1: Area under the concentration-time curve from time zero to the last quantifiable concentration (AUC[0-t]) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 1: Area under the concentration-time curve extrapolated from time zero to infinity (AUC[0-infinity]) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 1: Maximum plasma concentration (Cmax) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 1: Plasma concentrations at 24 hours (C24h) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose in each treatment period

Part 1: Time to Cmax (Tmax) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 1: Lag time for absorption (tlag) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 1: Terminal elimination half-life (T1/2) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 2: Area under the concentration-time curve over the dosing interval tau (AUC[0-tau]) after repeat dose administration of GSK3882347

Timeframe: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose

Part 2: Cmax after repeat dose administration of GSK3882347

Timeframe: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose

Part 2: Tmax after repeat dose administration of GSK3882347

Timeframe: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose

Part 2: Plasma concentrations over the dosing interval (Ctau) after repeat dose administration of GSK3882347

Timeframe: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose

Part 1: Urine concentration between 22-24 hours (C22-24) after single dose administration of GSK3882347

Timeframe: Day 1: 22-24 hours post-dose in each treatment period

Part 2: Urine concentration between 22-24 hours (C22-24) after repeat dose administration of GSK3882347

Timeframe: Day 1 and Day 7: 22-24 hours post-dose

Part 1: Amount of drug excreted in urine of unchanged drug (Ae Total) after single dose administration of GSK3882347

Timeframe: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48-60, 60-72, 72-84, 84-96 hours post-dose in each treatment period

Part 2: Amount of drug excreted in urine of unchanged drug (Ae Total) after repeat dose administration of GSK3882347

Timeframe: Days 1 and 7: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hours post-dose

Part 1: Percentage of the given dose of drug excreted in urine (%fe total) after single dose administration of GSK3882347

Timeframe: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48-60, 60-72, 72-84, 84-96 hours post-dose in each treatment period

Part 2: Percentage of the given dose of drug excreted in urine (%fe total) after single dose administration of GSK3882347

Timeframe: Day 1 and Day 7: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hours post-dose

Part 1: Renal clearance of drug (CLr) after single dose administration of GSK3882347

Timeframe: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48-60, 60-72, 72-84, 84-96 hours post-dose in each treatment period

Part 2: Renal clearance of drug (CLr) after repeat dose administration of GSK3882347

Timeframe: Day 1 and Day 7: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hours post-dose

Secondary outcomes:

Part 1: Area under the concentration-time curve from time zero to 12 hours (AUC[0-12]) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose in each treatment period

Part 1: Plasma concentrations at 12 hours (C12) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose in each treatment period

Part 1: Apparent oral clearance (CL/F) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 1: Apparent volume of distribution after oral administration (Vz/F) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 1: Mean residence time (MRT) after single dose administration of GSK3882347

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 2: Area under the concentration-time curve from time zero to 12 hours (AUC[0-12]) after repeat dose administration of GSK3882347

Timeframe: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose

Part 2: Plasma concentrations at 12 hours (C12) after repeat dose administration of GSK3882347

Timeframe: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose

Part 1: Dose Proportionality of GSK3882347 for Dose levels 15 mg to 900 mg using AUC(0-infinity) after single dose administration of GSK3882347 under fasted condition

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 1: Dose Proportionality of GSK3882347 for Dose levels 15 mg to 900 mg using Cmax after single dose administration of GSK3882347 under fasted condition

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period

Part 2: Dose Proportionality of GSK3882347 for Dose levels 50 mg to 900 mg using AUC(0-tau) after repeat dose administration of GSK3882347

Timeframe: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose

Part 2: Dose Proportionality of GSK3882347 for Dose levels 50 mg to 900 mg using Cmax after repeat dose administration of GSK3882347

Timeframe: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose

Part 2: Observed accumulation ratio (Ro) using AUC(0-tau) after repeat dose administration of GSK3882347

Timeframe: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose

Part 2: Time invariance of GSK3882347

Timeframe: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose

Part 2: Pre-dose plasma concentrations after repeat dose administration of GSK3882347 from Days 3 to 7

Timeframe: Days 3, 4, 5, 6 and 7: Pre-dose

Part 1: Area under the concentration-time curve from time zero to 24 hours (AUC[0-24]) after single dose administration of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose

Part 1: Area under the concentration-time curve from time zero to the last quantifiable concentration (AUC [0-t]) after single dose administration of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose

Part 1: Area under the concentration-time curve extrapolated from time zero to infinity (AUC [0-infinity]) after single dose administration of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose

Part 1: Maximum plasma concentration (Cmax) after single dose administration of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose

Part 1: Plasma concentrations at 24 hours (C24h) after single dose administration of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose

Part 1: Tmax after single dose administration of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose

Part 1: Tlag after single dose administration of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect

Timeframe: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose

Interventions:
  • Drug: GSK3882347
  • Drug: Placebo
    • Enrollment:
    61
    Primary completion date:
    2021-14-05
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Urinary Tract Infections
    Product
    GSK3882347
    Collaborators
    Biomedical Advanced Research and Development Authority (BARDA), Wellcome Trust
    Study date(s)
    August 2020 to May 2021
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 50 Years
    Accepts healthy volunteers
    Yes
    • Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
    • Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) not specifically listed in the exclusion or exclusion criteria that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor (if required), agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
    • Participants with history or presence of cardiovascular, respiratory, hepatic, urological, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data
    • Alanine transaminase (ALT) greater than 1.5 times upper limit of normal (ULN).
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
    • Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) not specifically listed in the exclusion or exclusion criteria that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor (if required), agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
    • Participants with Body weight at least 50.0 kilograms (kg) (110 pound [lbs]) for males and 45.0 kg (99 lbs.) for females; and body mass index (BMI) within the range 18.5
    • 32.0 kilograms per meter square (kg/m^2) (inclusive).
    • Male and female participants; a female participant is eligible to participate if she is of WONCBP; Male participants are eligible to participate if they agree to the following during the intervention period for at least five days, corresponding to time needed to eliminate study intervention(s) (e.g. 5 terminal half-lives) after the last dose of study intervention), refrain from donating sperm, be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; must agree to use contraception/barrier, agree to use a male condom.
    • Capable of giving signed informed consent as described in which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    Exclusion criteria:
    • Participants with history or presence of cardiovascular, respiratory, hepatic, urological, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data
    • Alanine transaminase (ALT) greater than 1.5 times upper limit of normal (ULN).
    • Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35%)
    • Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).
    • Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
    • Male participants with heart rate of less than 45 or greater than 100 beats per minute (bpm), females with less than 50 or greater than 100 bpm.
    • Participants with PR interval less than 120 or greater than 220 milliseconds (msec); QRS duration less than 70 msec or greater than 120 msec; QTcF interval greater than 450 msec.
    • Evidence of previous myocardial infarction on ECG (does not include ST segment changes associated with re-polarization).
    • Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolff-Parkinson-White [WPW] syndrome).
    • Sinus Pauses greater than 3 seconds.
    • Any significant arrhythmia which, in the opinion of the Investigator or GSK Medical Monitor, will interfere with the safety for the individual participant.
    • Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).
    • Current or history of renal disease, or estimated creatinine clearance <90 milliliter (mL)/minute/1.73meter^2 or serum creatinine greater than ULN at screening.
    • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the first dose of study intervention, unless in the opinion of the Investigator and the GSK medical monitor, the medication will not interfere with the study procedures or compromise participant safety.
    • Use of a systemic antimicrobial within 30 days of screening.
    • Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days.
    • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
    • Current enrolment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
    • Positive human immunodeficiency virus (HIV) antibody test.
    • Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
    • Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
    • Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
    • Positive pre-study drug/alcohol screen.
    • Any history of substance abuse or a positive test for drugs of abuse at screening or admission.
    • A positive highly sensitive pregnancy test (urine or serum as required by local regulations) at screening.
    • A positive laboratory confirmation of COVID-19 infection, or high clinical index of suspicion for COVID-19.
    • Part 1 (Food Effect): Participant must have no dietary restrictions (e.g., lactose intolerance) or inability to eat a high fat meal.
    • Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of greater than 21 units for males or greater than 14 units for females. One unit is equivalent to approximately (250 mL) of beer, (100 mL) of wine or (35 mL) measure of spirits.
    • Positive smoke breathalyzer indicative of smoking history at screening and each in-house admission to the clinical research unit or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening.
    • Hypersensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

    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
    Study complete
    Actual primary completion date
    2021-14-05
    Actual study completion date
    2021-14-05

    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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