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Infections, BacterialPhase 1NCT04493931

Drug-drug Interaction Study of Gepotidacin

A Phase 1 study testing Gepotidacin, Cimetidine and Rifampicin in people with Infections, Bacterial, run by GlaxoSmithKline at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Infections, Bacterial
What is being tested?
Gepotidacin, Cimetidine and Rifampicin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
64 participants
Where
1 siteUnited States
Study dates
14 Aug 2020to 21 Dec 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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).
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  • 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.
  • 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.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Las Vegas, Nevada, 89113

Other trials in United States

About this study

Official title: A Pharmacokinetic, Multi-cohort Study in Healthy Adult Subjects to Assess Gepotidacin as Victim and as Perpetrator of Drug-Drug Interactions Via CYP450, Renal and Intestinal Transporters, and to Assess Gepotidacin Pharmacokinetics in Japanese Healthy Adults

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.

Being tested
Gepotidacin, Cimetidine, Rifampicin, Midazolam, Digoxin
Keywords
Gepotidacin, Drug Interaction, Pharmacokinetic, Safety, Bacterial Infection, Japanese Healthy Adults
Medical subject headings
Bacterial Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GepotidacinDrug

    Also called GSK2140944

    Gepotidacin tablets will be available as unit dose strength 750 mg and will be administered orally.

  • CimetidineDrug

    Cimetidine tablets will be available as unit dose strength 400 mg and will be administered orally.

  • RifampicinDrug

    Rifampicin Capsules will be available as unit dose strength 300 mg and will be administered orally.

  • MidazolamDrug

    Midazolam oral syrup 2 milligrams per milliliter (mg/mL) will be available to be administered orally.

  • DigoxinDrug

    Digoxin tablets will be available as unit dose strength 0.25 mg and will be administered orally.

  • Placebo matching to gepotidacinOther

    Placebo matching to gepotidacin tablets will be administered orally.

Study groups in NCT04493931
Study groupRoleWhat they receive
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mgExperimentalThis is a fixed sequence (Sequence AB) cohort. Participants will receive gepotidacin 1500 milligrams (mg) single dose (SD) on Day 1 of Period 1 (Treatment A); and Cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 and gepotidacin 1500 mg single dose (Treatment B). Gepotidacin will be administered 1 hour after the first dose of cimetidine on Day 2 of Period 2. There will be a washout of at least 3 days between Treatment A and Treatment B, and a follow-up visit 5 to 7 days after the last dose of cimetidine.
Receives: Drug: Gepotidacin; Drug: Cimetidine
Cohort 2: Gepotidacin 1500 mg + Rifampicin 600 mgExperimentalThis is a fixed sequence (Sequence CDE) cohort. Participants will receive gepotidacin 1500 mg single dose on Day 1 of Period 1 (Treatment C), rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7 of Period 2, to elicit maximal enzyme induction) (Treatment D); and gepotidacin 1500 mg single dose administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 (Treatment E). There will be a washout of at least 3 days between Treatment C and Treatment D, and a follow-up visit 7 to 10 days after the last dose of rifampicin.
Receives: Drug: Gepotidacin; Drug: Rifampicin
Cohort 3: Digoxin 0.5mg+Midazolam 2mg then Gepotidacin 3000mgExperimentalParticipants will receive digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 1 on Day 1 then gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 2 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G). There will be a washout of at least 10 days between treatments. In Sequence 2, these regimens are reversed. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2.
Receives: Drug: Gepotidacin; Drug: Midazolam; Drug: Digoxin
Cohort 3: Gepotidacin 3000mg then Digoxin 0.5mg+Midazolam 2mgExperimentalParticipants will receive gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 1 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G) followed by digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 2 on Day 1. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2.
Receives: Drug: Gepotidacin; Drug: Midazolam; Drug: Digoxin
Cohort 4: Gepotidacin 1500 mg fed then fasted then 3000 mg fedExperimentalCohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fed conditions in Period 1 (Treatment H), then a single dose of gepotidacin 1500 mg under fasted conditions in Period 2 (Treatment I), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin.
Receives: Drug: Gepotidacin
Cohort 4: Gepotidacin 1500 mg fasted then fed then 3000 mg fedExperimentalCohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fasted conditions in Period 1 (Treatment I), then a single dose of gepotidacin 1500 mg under fed conditions in Period 2 (Treatment H), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin.
Receives: Drug: Gepotidacin
Cohort 4: Placebo fed then fasted then fedPlacebo comparatorCohort 4 will include Japanese participants. Participants will receive a single dose of placebo under fed conditions in Period 1, then a single dose of placebo under fasted conditions in Period 2, followed by two doses of placebo (given 12 hours apart) under fed conditions in Period 3. There will be a washout of at least 3 days between each period, and a follow-up visit 5 to 7 days after the last dose of placebo.
Receives: Other: Placebo matching to gepotidacin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric least square (LS) mean and 90 percent (%) confidence interval (CI) of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  2. Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  3. Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  4. Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  5. Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  6. Cohort 2: Cmax of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  7. Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  8. Cohort 2: Tmax of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  9. Cohort 2: AUC(0-t) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  10. Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  11. Cohort 3: Cmax of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  12. Cohort 3: Tlag of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  13. Cohort 3: Tmax of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  14. Cohort 3: AUC(0-t) of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  15. Cohort 3: AUC(0-infinity) of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  16. Cohort 3: Cmax of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  17. Cohort 3: Tlag of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  18. Cohort 3: Tmax of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  19. Cohort 3: AUC(0-t) of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  20. Cohort 3: AUC(0-infinity) of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  21. Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  22. Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  23. Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2

  24. Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  25. Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  26. Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  27. Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  28. Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  29. Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  30. Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  31. Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  32. Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  33. Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  34. Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  35. Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24 Hours post-dose in Treatment Period 3

  36. Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48 Hours post-dose in Treatment Period 3

  37. Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  38. Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

    Measured: Up to 22 days

  39. Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory (lab) value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 (%). High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 22 days

  40. Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, Blood Urea Nitrogen (BUN). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 22 days

  41. Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

    Urine samples were collected at indicated time points for the analysis of urinalysis parameters including potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 22 days

  42. Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

    Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 22 days

  43. Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval

    A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the Bazett formula (QTcB) Interval and corrected QT interval using the Fridericia formula (QTcF) Interval has been reported.

    Measured: Up to 22 days

  44. Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  45. Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  46. Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  47. Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  48. Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

Secondary outcomes (90)

  1. Cohort 1: AUC (0-24) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in each Treatment Periods 1 and 2

  2. Cohort 1: AUC(0-48) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  3. Cohort 1: Tlag of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  4. Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  5. Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  6. Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

  7. Cohort 1: AUC(0-24) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours Post-dose in each Treatment periods 1 and 2

  8. Cohort 1: AUC(0-48) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

  9. Cohort 1: Renal Clearance (CLr) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

  10. Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Measured: 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment periods 1 and 2

  11. Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 percent (%).

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

  12. Cohort 1: Number of Participants With SAE and Non-SAE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

    Measured: Up to 17 days

  13. Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 %. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 17 days

  14. Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 17 days

  15. Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

    Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 17 days

  16. Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

    Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 17 days

  17. Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

    A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.

    Measured: Up to 17 days

  18. Cohort 2: AUC(0-24) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2

  19. Cohort 2: AUC(0-48) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  20. Cohort 2: T1/2 of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  21. Cohort 2: Vz/F of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  22. Cohort 2: CL/F of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  23. Cohort 2: Ae Total of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  24. Cohort 2: AUC(0-24) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2

  25. Cohort 2: AUC(0-48) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  26. Cohort 2: CLr of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  27. Cohort 2: Ae(t1-t2) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Measured: 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  28. Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  29. Cohort 2: Number of Participants With SAE and Non-SAE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

    Measured: Up to 26 days

  30. Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 26 days

  31. Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 26 days

  32. Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

    Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 26 days

  33. Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

    Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 26 days

  34. Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

    A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.

    Measured: Up to 26 days

  35. Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  36. Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  37. Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  38. Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  39. Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  40. Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  41. Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  42. Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  43. Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  44. Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24 Hours post-dose in each Treatment Periods 1 and 2

  45. Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48 Hours post-dose in each Treatment Periods 1 and 2

  46. Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  47. Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  48. Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  49. Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  50. Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

  51. Cohort 3: T1/2 of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

  52. Cohort 3: Vz/F of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

  53. Cohort 3: CL/F of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

  54. Cohort 3: Cmin of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  55. Cohort 3: T1/2 of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  56. Cohort 3: Vz/F of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  57. Cohort 3: CL/F of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  58. Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  59. Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  60. Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  61. Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in each Treatment Periods 1 and 2

  62. Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  63. Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  64. Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  65. Cohort 3: Number of Participants With SAE and Non-SAE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

    Measured: Up to 30 days

  66. Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 30 days

  67. Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 30 days

  68. Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

    Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 30 days

  69. Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

    Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Measured: Up to 30 days

  70. Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

    A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.

    Measured: Up to 30 days

  71. Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  72. Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  73. Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  74. Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  75. Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  76. Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  77. Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  78. Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  79. Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  80. Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2

  81. Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  82. Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100%.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  83. Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  84. Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

  85. Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

  86. Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

  87. Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in Treatment Period 3

  88. Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in Treatment Period 3

  89. Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

  90. Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Measured: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2020
  2. Study start14 Aug 2020
  3. Primary completion21 Dec 2020
  4. Study completion21 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Cohort 1 and 2 are open-label, fixed sequence DDI cohorts. Cohort 3 is an open-label, 2-sequence, 2-period crossover randomized DDI cohort. Cohort 4 is a double-blind, placebo-controlled, randomized sequence study to investigate the safety and PK of gepotidacin.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04493931
Sponsor's protocol ID
213678
Status last verified
Dec 2021
First submitted
28 Jul 2020
Last updated
4 Mar 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Gepotidacin, Cimetidine and Rifampicin in people with Infections, Bacterial, run by GlaxoSmithKline at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma (time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2). The study lists 48 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04493931.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2022.

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