Pharmacokinetics of Gepotidacin Tablets in Adults and Adolescents Subjects
Condition: Infections, Bacterial
MeSH terms: Bacterial Infections
Intervention: Gepotidacin; Placebo
Intervention description: Tablets containing gepotidacin mesylate with a unit dose of 750 mg will be administered orally with 240 milliliter (mL) of water.; Tablets containing unit dose of placebo matching of gepotidacin will be administered orally with 240 mL of water.
Intervention MeSH terms: Gepotidacin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Part 1 is a 3-period, fixed-sequence study of a single 1500-mg dose (Period 1) and two 3000-mg doses of gepotidacin at Hours 0 and 12 (Period 2) and Hours 0 and 6 (Period 3) in healthy adult subjects. Part 2 is a 2-period, fixed sequence study of a single 1500 mg dose (Period 1) of gepotidacin and two 3000 mg doses (Period 2) of gepotidacin in healthy adolescent subjects. .
Masking: Double (Participant, Investigator)
Masking description: This is a double-blind study.
Enrollment: 34.0
Sex: All
Minimum age: 12 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: GSK2140944; Gepotidacin; Pharmacokinetics; Healthy Adult; Healthy adolescent

Summary:

      This is double-blind, randomized, sequential, two part study. Part 1 is a 3 periods,
      fixed-sequence study and will be conducted to evaluate the pharmacokinetics, safety, and
      tolerability of the gepotidacin tablet in healthy adult subjects. Part 2 is a 2 periods,
      fixed-sequence study and will evaluate the pharmacokinetics, safety, and tolerability of the
      gepotidacin tablet in healthy adolescent subjects. The primary purpose of Part 1 is to
      evaluate the pharmacokinetics of a single 1500 milligram (mg) dose and two 3000 mg doses of
      gepotidacin given 6 and 12 hours apart in adult subjects; Part 2 is to evaluate the
      pharmacokinetics of a single 1500 mg dose and two 3000 mg doses of gepotidacin given at a
      dosing interval (to be determined based on the pharmacokinetic and safety results from Part
      1) in adolescent subjects. The duration of Part A will be approximately 47 days and 52 days
      for Part 2.
    

Eligibility criteria:

        Inclusion Criteria

          -  Subjects in Part 1 must be >=18 to <=64 years of age inclusive, at the time of signing
             the informed consent.

          -  Subjects in Part 2 must be >=12 to <18 years of age inclusive, at the time of signing
             the informed consent/assent.

          -  Subjects who are healthy as determined by the investigator or medically qualified
             designee based on medical evaluation including medical history, physical examination,
             clinical laboratory tests, vital sign measurements, and 12-lead ECG results <450
             millisecond (msec). A subject with clinical abnormality or laboratory parameters
             outside the reference range for the population being studied may be included only if
             the investigator feels and documents that the finding is unlikely to introduce
             additional risk factors and will not interfere with the study procedures.

          -  Body weight >=40 kilogram (kg) and body mass index (BMI) within the range 18.5 - 32.0
             kg per square meter (inclusive).

          -  Male and/or female.

          -  Female subjects: A female subject is eligible to participate if she is not pregnant or
             breastfeeding, and at least one of the following conditions applies: a) Is not a woman
             of childbearing potential (WOCBP), or b) Is a WOCBP and using a contraceptive method
             that is highly effective, with a failure rate of <1% for at least 30 days prior to
             dosing until completion of the follow-up visit. The investigator should evaluate the
             effectiveness of the contraceptive method in relationship to the first dose of study
             intervention. A WOCBP must have a highly sensitive negative pregnancy test before the
             first dose of study intervention.

          -  Capable of giving signed informed consent/assent which includes compliance with the
             requirements and restrictions listed in the informed consent form/assent and protocol.

        Exclusion Criteria

          -  Clinically significant abnormality in the past medical history or at the screening
             physical examination that in the investigator's opinion may place the subject at risk
             or interfere with outcome variables of the study. This includes, but is not limited
             to, history or current cardiac, hepatic, renal, neurologic, gastrointestinal (GI),
             respiratory, hematologic, or immunologic disease.

          -  Any surgical or medical condition (active or chronic) that may interfere with drug
             absorption, distribution, metabolism, or excretion of the study intervention, or any
             other condition that may place the subject at risk, in the opinion of the
             investigator.

          -  Female subject has a positive pregnancy test result or is lactating at screening or
             upon admission to the clinic.

          -  Use of any systemic antibiotic within 30 days of screening.

          -  Within 2 months before screening, either a confirmed history of Clostridium difficile
             diarrhea infection or a past positive of Clostridium difficile toxin test.

          -  Current or chronic history of liver disease or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  History of drug and/or alcohol abuse within 6 months before screening, as determined
             by the investigator, or has a positive drug screen at screening or upon admission to
             the clinic.

          -  History of sensitivity to any of the study drug, components thereof, or a history of
             drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline
             medical monitor contraindicates their participation.

          -  History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinic
             uses heparin to maintain intravenous cannula patency).

          -  Subject must abstain from taking prescription or non-prescription drugs (except for
             hormonal contraceptives and/or acetaminophen), vitamins, and dietary or herbal
             supplements, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5
             half-lives (whichever is longer) prior to study intervention until completion of the
             follow-up visit, unless, in the opinion of the investigator and sponsor, the
             medication will not interfere with the study. Any exceptions will be discussed with
             the sponsor or medical monitor on a case-by-case basis and the reasons will be
             documented.

          -  Previous exposure to gepotidacin within 12 months prior to starting study
             intervention.

          -  Subject has participated in a clinical trial and has received an investigational
             product prior to gepotidacin administration within 30 days, 5 half-lives, or twice the
             duration of the biological effect of investigational product (whichever is longer).

          -  Presence of hepatitis B surface antigen or positive hepatitis C antibody test result
             at screening or within 3 months prior to starting study intervention.

          -  ALT >1.5 * upper limit of normal (ULN).

          -  Bilirubin >1.5 * ULN (isolated bilirubin >1.5 * ULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35%).

          -  History of any kidney disease or current or chronic history of impaired renal function
             as indicated by an estimated creatinine clearance <60 milliliter per minute (mL/min).

          -  A positive test for human immunodeficiency virus antibody.

          -  History of regular alcohol consumption within 6 months of screening defined as an
             average weekly intake of >21 units (or an average daily intake of >3 units) for males
             or an average weekly intake of >14 units (or an average daily intake >2 units) for
             females. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer,
             30 mL of spirits, or 100 mL of wine.

          -  Urinary cotinine level indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products within 3 months before screening.

          -  Clinically significant abnormal findings in serum chemistry, hematology, or urinalysis
             results obtained at screening or Day -1.

          -  Baseline corrected QT interval using the Fridericia formula (QTcF) of >450 msec.

          -  Subject has donated blood in excess of 500 mL within 12 weeks prior to dosing or
             participation in the study would result in donation of blood or blood products in
             excess of 500 mL within a 56-day period.

          -  Subject is unable to comply with all study procedures, in the opinion of the
             investigator.

          -  Subject should not participate in the study, in the opinion of the investigator or
             sponsor.