Safety, Tolerability and Pharmacokinetic Investigation of GSK3882347 in Healthy Participants.
Condition: Urinary Tract Infections
MeSH terms: Urinary Tract Infections
Intervention: GSK3882347; Placebo
Intervention description: Capsule of 10-200mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.; Matching strength placebo capsules will be provided
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Part 1 will consist of two cohorts (Cohorts 1 and 2) with a maximum of four periods in a cross-over design conducted in two separate cohorts. Part 2 consists of a maximum of four ascending repeat-dose cohorts (Cohorts 3 to 6) for which participants, will receive a single oral dose of GSK3882347 or placebo for 7 days.
Masking: Double (Participant, Investigator)
Masking description: This will be a double-blind study with participants and the site staff blinded.
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: SAD; MAD; FTIH; Pharmacokinetics; Urinary Tract Infections; GSK3882347

Summary:

      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.
    

Eligibility 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.