Drug-drug Interaction Study of Gepotidacin

This study is a drug-drug interaction (DDI), pharmacokinetics (PK), safety and tolerability study in adult healthy participants, including Japanese cohort. This study is designed to assess co-administration of probe substrates with gepotidacin in study cohorts 1 to 3 and establishing PK and safety in Japanese participants in cohort 4. Food effect will also be evaluated in cohort 4.


Eligibility Criteria:
Inclusion Criteria:

* Participant must be greater than or equal to (\>=) 18 to less than or equal to (=\<) 50 years of age inclusive, at the time of signing the informed consent.
* Participants 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. A participant 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.
* Additional inclusion criteria for Japanese participants (Cohort 4): The participant is a non-naturalized Japanese citizen and holds a Japanese passport (current or expired).

The participant has/had 2 Japanese parents and 4 Japanese grandparents who are/were all non-naturalized Japanese citizens, as confirmed by interview.

The participant has been living outside of Japan for up to 10 years as confirmed by interview.

* Participants have a body weight \>=40 kilograms (kg) and body mass index within the range 18.5 to 32.0 kilograms per square meter (kg/m\^2) (inclusive).
* Male and/or female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

  1. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is a woman of non-childbearing potential or Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of \<1 percent (%), for at least 30 days prior to dosing until completion of the follow-up Visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.

A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention and for women not on effective contraception at least 14 days prior to baseline visit.

The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the 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 participant at risk or interfere with the outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastro-intestinal (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 participant at risk, in the opinion of the investigator.
* Female participant has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic.
* Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Note: Testing will be performed according to site procedures.
* Within 2 months before Screening, either a confirmed history of Clostridium difficile (C. difficile) diarrhea infection or a past positive of C. 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/hypersensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor contraindicates their participation.
* Cohort 2 Only: Participant is a contact lens wearer who is unable or unwilling to wear glasses for the duration of the study and for 5 half-lives after the last dose of rifampicin.
* Use of any systemic antibiotic within 30 days of screening.
* Participants must abstain from taking prescription or non-prescription drugs (except for hormonal contraceptives and/or acetaminophen at doses of \<=2 grams/day), 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.
* Participant has participated in a clinical trial and has received an investigational product (IP) prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of IP (whichever is longer).
* Past participation in this clinical study.
* Baseline corrected QT interval using the Fridericia formula (QTcF) of \>450 milliseconds (msec) at Screening or Check-in.
* Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention.
* Alanine aminotransferase (ALT) \>1.5 times upper limit of normal (ULN) at Screening or Check-in.
* Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) at Screening or Check-in.
* History of any kidney disease or current or chronic history of mild impaired renal function as indicated by an estimated creatinine clearance \<=90 milliliters per minute (mL/min).
* A positive test for human immunodeficiency virus (HIV) 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.
* Cohort 3 Only: Digoxin-related exclusions include the following at Screening:

Serum potassium \>5.5 milliequivalent per liter (mEq/L) or \< 3.6 mEq/L Serum magnesium \<1.6 milligrams per deciliter (mg/dL) Serum calcium (total) \<8.5 mg/dL History of hypersensitivity to digoxin or other digitalis glycosides Any clinically relevant abnormality on 12-lead ECG at Screening or Check-in.

* Participant 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.
* Participant is unable to comply with all study procedures, in the opinion of the investigator.
* Participant should not participate in the study, in the opinion of the investigator or Sponsor.