Thorough QT/QTC (TQT) Clinical Trial to Evaluate the Effect of Zoliflodacin on Cardiac Repolarization in Healthy Male and Female Subjects

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03613649
• Collaborator: (none)
• Enrollment: 72
• Location: 1
• Arms: 4
• Actual Duration (Months): 3.3
• Patients Per Site Per Month: 22.1

Study Details

Study Description

Brief Summary

The Phase I Thorough QT/QTc (TQT) study will be performed in a single center, the Vince & Associates Clinical Research, Inc., clinical trials unit (CTU), in 72 healthy male or female subjects, aged 18 to 45 years inclusive, to evaluate the effect of zoliflodacin on the corrected QT interval of the electrocardiogram (ECG) using Fridericia's Formula (QTcF) and other ECG parameters; the correlation of the drug concentrations (and pharmacokinetic (PK) profile) with time-matched, placebo-corrected, baseline-adjusted difference in QTcF interval (delta delta QTcF); and the PK and safety profiles of the new zoliflodacin formulation. Each subject will receive one dose of each of four treatments: zoliflodacin 2 g orally, zoliflodacin 4 g orally, placebo for zoliflodacin 4 g orally, and moxifloxacin 400 mg orally. The study will last approximately 12 weeks with a subject participation duration of up to 55 days. The primary hypothesis to be tested is that following administration of zoliflodacin 2 g and 4 g, the upper bound of the one-sided 95% confidence interval (CI) of treatment effect on delta delta QTcF is > / = 10 msec for at least one of the ECG assessments, against the alternative hypothesis that all mean effects are < 10 msec. The primary objective is to evaluate the effect of zoliflodacin on the corrected QT interval of the ECG using Fridericia's formula (QTcF).

Condition or Disease	Intervention/Treatment	Phase
Electrocardiogram Repolarisation Abnormality; Gonococcal Infection	Drug: AZD0914; Drug: Moxifloxacin; Other: Placebo	Phase 1

Detailed Description

The Phase I Thorough QT/QTc (TQT) study will be performed in a single center, the Vince & Associates Clinical Research, Inc., clinical trials unit (CTU), according to a randomized, double-blinded (except for the use of moxifloxacin), placebo-controlled, four-period, four-treatment, crossover design balanced with respect to first-order carryover effect in 72 healthy male or female subjects, aged 18 to 45 years inclusive, to evaluate the effect of zoliflodacin on the corrected QT interval of the electrocardiogram (ECG) using Fridericia's Formula (QTcF) and other ECG parameters; the correlation of the drug concentrations (and pharmacokinetic (PK) profile) with time-matched, placebo-corrected, baseline-adjusted difference in QTcF interval (delta delta QTcF); and the PK and safety profiles of the new zoliflodacin formulation. Each subject will receive one dose of each of four treatments: zoliflodacin 2 g orally, zoliflodacin 4 g orally, placebo for zoliflodacin 4 g orally, and moxifloxacin 400 mg orally. The study will last approximately 12 weeks with a subject participation duration of up to 55 days. The primary hypothesis to be tested is that following administration of zoliflodacin 2 g and 4 g, the upper bound of the one-sided 95% confidence interval (CI) of treatment effect on delta delta QTcF is > / = 10 msec for at least one of the ECG assessments, against the alternative hypothesis that all mean effects are < 10 msec. The primary objective is to evaluate the effect of zoliflodacin on the corrected QT interval of the ECG using Fridericia's formula (QTcF). The secondary objectives are: 1) to evaluate the effects of zoliflodacin on other ECG parameters (PR, QRS, and RR intervals, and heart rate (HR)); 2) to evaluate the sensitivity of QTcF measurement using moxifloxacin; 3) to evaluate the effect of zoliflodacin on T-wave morphology; 4) to evaluate the PK of 2 g and 4 g oral zoliflodacin under fasting state; 5) to evaluate the relationship between zoliflodacin PK and time-matched QTcF pharmacodynamics (PD); 6) to evaluate the safety and tolerability of 2 g and 4 g oral zoliflodacin.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Randomized, Double-blinded, Four-period Crossover, Thorough QT/QTC (TQT) Clinical Trial to Evaluate the Effect of Zoliflodacin on Cardiac Repolarization in Healthy Male and Female Subjects
• Actual Study Start Date: Sep 25, 2018
• Actual Primary Completion Date: Jan 2, 2019
• Actual Study Completion Date: Jan 2, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A 2 g of zoliflodacin administered orally on Day 1 of each dosing period, n=72	Drug: AZD0914; Spiropyrimidinetrione antibacterial drug, which inhibits bacterial DNA synthesis by a novel mechanism. Powder will be reconstituted in 60 mL of tap water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin is taken, approximately 60 mL of tap water will be added to the cup and consumed by the subject to chase the initial dose.
Experimental: Treatment B 4 g of zoliflodacin administered orally on Day 1 of each dosing period, n=72	Drug: AZD0914; Spiropyrimidinetrione antibacterial drug, which inhibits bacterial DNA synthesis by a novel mechanism. Powder will be reconstituted in 60 mL of tap water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin is taken, approximately 60 mL of tap water will be added to the cup and consumed by the subject to chase the initial dose.
Placebo Comparator: Treatment C Placebo for zoliflodacin administered orally on Day 1 of each dosing period, n=72	Other: Placebo; Composed of 4 g of the same excipients found in zoliflodacin. Powder will be reconstituted in 60 mL of tap water and dosed orally after an overnight fast. After the cup containing 60 mL of placebo is taken, approximately 60 mL of tap water will be added to the cup and consumed by the subject to chase the initial dose.
Active Comparator: Treatment D 400 mg of moxifloxacin administered orally on Day 1 of each dosing period, n=72	Drug: Moxifloxacin; Broad-spectrum 8-methoxy fluoroquinolone with activity against both Gram-positive and Gram-negative bacteria, including anaerobes. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride will be administered orally with 120 mL of tap water.

Outcome Measures

Primary Outcome Measures

1. The One-sided 95% Confidence Interval (CI) for the Largest Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin [Baseline, 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose after 2 and 4 g zolifloadacin]

   Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline QTcF intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

Secondary Outcome Measures

1. Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

   Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline heart rate by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

2. Time-matched, Placebo-corrected, Baseline-adjusted, the Time From the Onset of the P Wave to the Start of the QRS Complex (PR Interval) Following Administration of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

   Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline PR intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

3. Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

   Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline RR intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

4. Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

   Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline QRS durations by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

5. The One-sided 95% Confidence Interval (CI) of the Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) After a Single Dose of Moxifloxacin [Baseline, 1 h, 2 h, 3 h, and 4 h post-dose]

   Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline QTcF intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

6. Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

   Categorical T-wave morphology analysis was collected in three ECG replicates at each timepoint (Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose). Abnormalities present in any one or more of the baseline timepoint replicate ECGs recorded for a particular period was considered to be present at baseline for post-dose ECGs from that specific period. If a subject had an ECG morphological abnormality in more than one replicate ECG of a study timepoint, the subject was counted only once for that timepoint. Flat is defined as T amplitude <1 mm (either positive or negative) including flat isoelectric line and Biphasic is defined as T-wave that contains a second component with an opposite phase that was at least 0.1 millivolts (mV) deep (both positive and negative/positive and polyphasic T-waves included).

7. Maximum Observed Concentration (Cmax) of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

   Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations computed from concentrations that were measured using a validated HPLC-MS/MS method. Pharmacokinetic (PK) parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

8. Time of Maximum Observed Concentration (Tmax) of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

   Tmax is defined as the time at which the maximum concentration (Cmax) occurs in plasma computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

9. Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0 - Infinity)) for Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

   AUC(0 - infinity) was defined as the total area under the concentration-time curve from dosing (time 0) taken to the limit as the end time becomes arbitrarily large. AUC(0 - infinity) was calculated by adding AUC(0-last) to an extrapolated value equal to the last measured concentration greater than the lower limit of quantification of the bioanalytical assay divided by the terminal phase elimination rate constant (Ke) computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

10. Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

    AUC(0-last) was defined as the area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

11. Apparent Volume of Distribution (Vz/F) of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

    Apparent volume of distribution during terminal phase (Vz/F) after non-intravenous administration was calculated as (CL/F)/ Ke computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

12. Apparent Oral Clearance (CL/F) of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

    Apparent oral clearance (CL/F) computed as Dose/Area under the curve (AUC) from time zero to infinity (0-infinity) computed from concentrations that were measured using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

13. Elimination Rate Constant (Ke) of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

    The terminal phase elimination rate constant (Ke) was defined as the first-order rate constant describing the rate of decrease of drug concentration in the terminal phase (defined as the terminal region of the PK curve where drug concentration follows first-order elimination kinetics) computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

14. Terminal Elimination Half-life (t1/2) of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

    The apparent terminal elimination half-life (t1/2) was defined as the time required for the drug concentration to decrease by a factor of one-half in the terminal phase computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

15. Relationship Between Plasma Concentrations of Zoliflodacin and Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin [Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose]

    One-sided 95% confidence intervals of population mean QTcF time-matched, placebo-corrected, baseline-adjusted mean QTcF interval at plasma concentration corresponding to the observed geometric mean Cmax for 2 g and 4 g doses of zoliflodacin were computed using a linear mixed effect model with PK and concentration data collected at baseline and intervals post-dose.

16. Number of Participants With Treatment-emergent Serious Adverse Events Following Administration of Zoliflodacin and Moxifloxacin [From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).]

    Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect.

17. Number of Participants With Treatment-emergent Adverse Events Following Administration of Study Product [From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).]

    Adverse events are defined as any untoward medical occurrence regardless of its causal relationship to the study treatment.

18. Changes From Baseline for Blood Pressure - Systolic [From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).]

    Change from baseline in systolic blood pressure was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

19. Changes From Baseline for Blood Pressure - Diastolic [From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).]

    Change from baseline in diastolic blood pressure was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

20. Changes From Baseline for Pulse Rate [From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).]

    Change from baseline in pulse rate was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

21. Changes From Baseline for Respiratory Rate [From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).]

    Change from baseline in respiratory rate was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

22. Changes From Baseline for Temperature [From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).]

    Change from baseline for temperature was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

23. Changes From Baseline for White Blood Cells With Differentials [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Hematology parameters included white blood cell count, and differential (absolute counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils).

24. Changes From Baseline for Hemoglobin [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline for hemoglobin is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

25. Changes From Baseline for Hematocrit [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline for hematocrit is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

26. Changes From Baseline for Erythrocytes [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline for erythrocytes is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

27. Changes From Baseline for Platelets [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline for platelets is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

28. Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included sodium, potassium. chloride and bicarbonate.

29. Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included magnesium, glucose (fasting), BUN, creatinine, total bilirubin, direct bilirubin

30. Changes From Baseline for Total Protein and Albumin [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included total protein and albumin.

31. Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included AST, ALT and AP.

32. Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated [Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).]

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

33. Occurrence of Urinalysis Adverse Events Following Administration of Study Product [From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).]

    Urine for the clinical laboratory test was collected on Day -1, 24 hour post dose and the check in for the following dosing period. The results for glucose dipstick, protein dipstick and occult blood - dipstick were reported in categorical results. The possibilities were negative, trace, 1+, 2+, and 3+. If the dipsticks were 1+ or greater, microscopic evaluations were performed for erythrocytes, leukocytes and bacteria. For microscopic results to be deemed abnormal, the results must be reported 6 or greater per high power field.

34. Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval [Baseline, 1 h, 2 h, 4h, 24 h post-dose and follow up]

    Change from baseline in ECG is calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, 24 h after dosing and prior to the next dose (follow up). The following ECG Parameters were analyzed: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex), QRS Duration (Time From the Start of the Q-wave to the End of the S-wave), QT Interval (Interval From Onset of the Q-wave to the End of the T-wave), QTcF Interval (QT Interval Corrected by Fridericia's Formula) and RR Interval (Interval From the Peak of the R Wave of a QRS Complex to the Peak of the R Wave of the Next QRS Complex).

35. Changes From Baseline in ECG Measures: Ventricular Rate [Baseline, 1 h, 2 h, 4h, 24 h post-dose and follow up]

    Change from baseline in ECG Ventricular Rate is calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, 24 h after dosing and prior to the next dose (follow up).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

All must be answered YES for the subject to be eligible for study participation:

1. Informed consent form (ICF) understood and signed before initiating any study procedures

2. Healthy male or female, as assessed by authorized site clinician (listed on FDA Form

1. Willingness to comply with and be available for all protocol procedures, including inpatient confinement for 3 days in each dosing period and follow-up for the duration of the trial

2. Aged 18 to 45 years inclusive on the day of first dosing

3. Body Mass Index (BMI) > / = 18.5 and < / = to 30 kg per m^2 and weight > / = 50 kg (110 lbs.) and < / = 100 kg (220 lbs.)

4. In all female subjects, whether of childbearing potential or post-menopausal by medical history (MH), a negative serum pregnancy test at Screening Visit and on Day -1 of each dosing period

-Note: A woman is considered of childbearing potential unless post-menopausal (> / = 1 year without menses without other known or suspected cause and with a FSH level in the menopausal range), or surgically sterilized (hysterectomy, salpingectomy, oophorectomy, or tubal ligation/occlusion).

1. If female, not pregnant, not breast feeding, and not planning to become pregnant during the trial and for 30 days after Final Visit

2. Females of childbearing potential and males agree to use acceptable contraception for the duration of the trial and for 30 days (females) or 90 days (males) after Final Visit

-Note: A highly effective method of birth control is defined as one with a low failure rate (i.e., less than 1 percent per year) according to CDC criteria. These include progestin implants, intrauterine devices (IUDs), surgical (hysterectomy, salpingectomy, oophorectomy, or tubal ligation/occlusion; vasectomy), or abstinence. Use of methods with higher failure rate (such as progestin injectables, combined oral hormonal contraceptives, condoms, and diaphragms) will not be acceptable when used alone, but they could be considered if used in combination with another method (e.g., a female using combined oral contraceptives if her male partner is sterile, or if she and her non-sterile male partner use a double-barrier method), after consultation with the DMID Medical Officer.

1. Male subjects agree to refrain from sperm donation for the duration of the trial and for 90 days after Final Visit

2. Laboratory tests are in the normal reference range with acceptable exceptions

3. Vital signs (VS) are within the acceptable range

4. Has adequate venous access for blood collection

5. Urine drug screen is negative for tested substances

6. Urine alcohol test is negative

7. Willing to abstain from alcohol consumption for 2 days before Day -1 of Period 1 and for the duration of the trial

Exclusion Criteria:

All must be answered NO for the subject to be eligible for study participation:

1. History of acute or chronic cardiovascular disease or surgery

• Note: Conditions include: congestive heart failure; coronary artery disease (myocardial infarction, unstable angina); cerebrovascular disease (cerebrovascular accident or stroke or transient ischemic attack (TIA); chronic hypertension; or coronary revascularization surgery (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) 2. History of cardiac arrhythmia or syncope related to cardiac arrhythmia or unexplained, or use of a cardiac pacemaker

• Note: Conditions include: atrial fibrillation, atrial flutter, or non-sustained or sustained ventricular tachycardia; use of a cardiac pacemaker; personal or family history of LQTS; or family history of sudden death 3. History of any other chronic medical or surgical condition that would interfere with the accurate assessment of the trial's objectives or increase the subject's risk profile

• Note: Chronic medical conditions include: diabetes mellitus; asthma requiring use of medication in the year before screening; autoimmune disorder such as lupus erythematosus, Wegener's, rheumatoid arthritis, thyroid disease; malignancy except low-grade (squamous and basal cell) skin cancer thought to be cured; chronic renal, hepatic, pulmonary, or endocrine disease, myopathy, or neuropathy; gastrointestinal surgery including weight loss surgery or biliary surgery 4. Major surgical interventions are not permitted within 4 weeks of first dosing and during the trial. Minor surgical interventions are not allowed within 2 weeks of first dosing and during the trial 5. History of hypersensitivity or severe allergic reaction of any type to medications, bee stings, food, or environmental factors

• Note: Severe allergic reaction is defined as any of the following: anaphylaxis, urticaria, or angioedema 6. Active allergic symptoms to seasonal and animal allergens that are moderate to severe, affect daily activity, and require continuous treatment

1. A marked baseline prolongation of ECG intervals, or HR less than 45 bpm or greater than 100 bpm on ECG measurements

• Note: The following are considered prolonged ECG intervals: QTc/QTcF > 449 msec in males and females; PR > 209 msec; and QRS > 110 msec 8. Clinically significant abnormal ECG results

• Note: Clinically significant abnormal ECG results include: complete left or right bundle branch block; other ventricular conduction block; 2nd degree or 3rd degree atrioventricular (AV) block; sustained atrial or ventricular arrhythmia; two premature ventricular contractions in a row; pattern of ST elevation felt consistent with cardiac ischemia; evidence of a previous myocardial infarction (MI), left ventricular hypertrophy (LVH), or more than minor non-specific ST-T wave changes; any characteristics that would make QT assessment unreliable, including flat T waves; or any condition deemed clinically significant by a study investigator 9. Abnormal renal function

• Note: Normal renal function is defined as normal creatinine and normal estimated glomerular filtration rate (eGFR) [i.e., > 80.0 mL/min] values according to Cockroft-Gault 10. Positive serology results for HIV, HBsAg, or HCV 11. Febrile illness with temperature > / = 38.0 degrees Celsius for < 7 days before dosing in each treatment period 12. Donated whole blood or blood products within 60 days before first dosing, or plans to donate or receive before Final Visit (Day 8 + / - 2 after last dose in dosing period 4)

• Note: Blood products include RBCs, white blood cells (WBCs), platelets, and plasma 13. Known allergic reactions to fluoroquinolones or to components present in the formulation or processing of zoliflodacin and moxifloxacin 14. Treatment with another investigational product within 30 days of first dosing or 5 half-lives or twice the duration of the biological effect of the study drug (whichever is longer)

• Note: Investigational products include a drug, vaccine, biologic, device, or blood product 15. Active drug or alcohol binge consumption, abuse, or dependence within 12 months before Screening Visit that, in the opinion of the investigator, would interfere with adherence to study requirements 16. Use of any prescription medication within 30 days before first dosing or planned use during the trial except as noted below and approved by the designated study clinician

• Note 1: Prohibited medications include moderate or strong CYP3A4 inducers and other drugs with known risk for QT prolongation and TdP; antibiotics; injectable or oral antidiabetic drugs; anti-lipid drugs; immunosuppressive agents; immune modulators; oral corticosteroids; anti-neoplastic agents; any vaccine (licensed or investigational) except licensed influenza vaccine during the flu season, which is allowed up to 7 days before first dosing or 7 days after last dosing

• Note 2: Allowed medications include: oral contraceptives; H1 antihistamines; all medications approved for control of intraocular pressure including topical ophthalmic non-selective beta-blockers, such as betaxolol, carteolol, levobunolol, metipranolol, and timolol; topical/ intranasal corticosteroids; nonsteroidal anti-inflammatory drugs (NSAIDS); licensed influenza vaccine during the flu season, 7 days before first dosing or 7 days after last dosing 17. Use of non-prescription medications, vitamins, herbs, or nutritional supplements within 15 days before first dosing or planned use during the trial unless approved by the study clinician

• Note 1: Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug-metabolizing enzymes and transporters (e.g., grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard], and charbroiled meats) within 7 days before dosing

• Note 2: Exceptions: St. John's wart is not allowed within 30 days of dosing; vitamins and over-the-counter (OTC) medications taken for a brief period (less than 48 h) for the treatment of common symptoms (such as headache, indigestion, muscle pain) may be allowed as approved by the designated study clinician 18. Intake of caffeinated beverages or food within 72 h before first dosing or a history of high caffeine consumption (e.g., in the last 4 months drinking > 5 cups of coffee/day) 19. Smoking or use of tobacco or nicotine-containing products within 30 days before first dosing

1. Engagement in strenuous exercise within 15 days before first dosing (e.g., marathon running, long-distance cycling, weight lifting) and during the trial 21. Any specific behavioral or clinical condition that, in the judgment of the investigator, precludes participation because it could affect compliance with study procedures or subject safety 22. Plans to enroll or is already enrolled in another clinical trial that could interfere with safety assessment of the study drug at any time during the trial

• Note: Includes trials that have a study intervention such as a drug, biologic, or device 23. Is a CTU employee or staff member who is paid entirely or partially by the Office of Clinical Research Resources (OCRR)/NIAID contract for the DMID-funded trial

• Note: CTU employees or staff include the PIs, sub-investigators, or staff who are supervised by the PI or sub-investigators

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vince and Associates Clinical Research	Overland Park	Kansas	United States	66212

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 27, 2018
• Statistical Analysis Plan - Dec 19, 2018

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03613649
• Other Study ID Numbers: 16-0110; HHSN272201500005I
• First Posted: Aug 3, 2018
• Last Update Posted: Mar 27, 2020
• Last Verified: May 7, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): AZD0914; Cardiac; ETX0914; Healthy; Moxifloxacin; Repolarization; Study; TQT; Volunteers; Zoliflodacin
• Additional relevant MeSH terms: Gonorrhea; Moxifloxacin

Study Results

Participant Flow

Recruitment Details	The trial was performed at a commercial phase 1 unit. Recruitment opened on September 4, 2018 and all 72 participants were consented and screened for meeting eligibility criteria prior to enrollment and dosing. Enrollment was completed on December 04, 2018.

Arm/Group Title	2g Zoliflodacin, 4g Zoliflodacin, Placebo, 400mg Moxifloxacin	2g Zoliflodacin, Placebo, 400mg Moxifloxacin, 4g Zoliflodacin	2g Zoliflodacin, 400mg Moxifloxacin, 4g Zoliflodacin, Placebo	4g Zoliflodacin, 2g Zoliflodacin, 400mg Moxifloxacin, Placebo	4g Zoliflodacin, 400mg Moxifloxacin, Placebo, 2g Zoliflodacin,	4g Zoliflodacin, Placebo, 2g Zoliflodacin, 400mg Moxifloxacin	Placebo, 400mg Moxifloxacin, 2g Zoliflodacin, 4g Zoliflodacin,	Placebo, 2g Zoliflodacin, 4g Zoliflodacin, 400mg Moxifloxacin	Placebo, 4g Zoliflodacin, 400mg Moxifloxacin, 2g Zoliflodacin	400mg Moxifloxacin, Placebo, 4g Zoliflodacin, 2g Zoliflodacin	400mg Moxifloxacin, 4g Zoliflodacin, 2g Zoliflodacin, Placebo	400mg Moxifloxacin, 2g Zoliflodacin, Placebo, 4g Zoliflodacin
Arm/Group Description	Treatment ABCD: 2 g of zoliflodacin administered orally on Day 1, then an 8 day wash out 4 g of zoliflodacin was taken, then another 8 day wash out placebo was taken and then after the final 8 day wash out 400mg of moxifloxacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment ACDB: 2 g of zoliflodacin administered orally on Day 1, then an 8 day wash out placebo was taken, then another 8 day wash out, 400 mg moxifloxacin was taken and then after the final 8 day wash out 4 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment ADBC: 2 g of zoliflodacin administered orally on Day 1, then an 8 day wash out 400mg of moxifloxacin was taken, then another 8 day wash out 4g of zoliflodacin was taken and then after the final 8 day wash out placebo was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment BADC: 4 g of zoliflodacin administered orally on Day 1, then an 8 day wash out 2 g of zoliflodacin was taken, then another 8 day wash out 400mg of moxifloxacin was taken and then after the final 8 day wash out placebo was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment BDCA: 4 g of zoliflodacin administered orally on Day 1, then an 8 day wash out 400mg of moxifloxacin was taken, then another 8 day wash out placebo was taken and then after the final 8 day wash out 2 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment BCAD: 4 g of zoliflodacin administered orally on Day 1, then an 8 day wash out placebo was taken, then another 8 day wash out 2 g of zoliflodacin was taken and then after the final 8 day wash out 400mg of moxifloxacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment CDAB: Placebo administered orally on Day 1, then an 8 day wash out 400mg of moxifloxacin was taken, then another 8 day wash out 2 g of zoliflodacin was taken and then after the final 8 day wash out 4 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment CABD: Placebo administered orally on Day 1, then an 8 day wash out 2 g of zoliflodacin was taken, then another 8 day wash out 4 g of zoliflodacin was taken and then after the final 8 day wash out 400mg of moxifloxacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment CBDA: Placebo administered orally on Day 1, then an 8 day wash out 4 g of zoliflodacin was taken, then another 8 day wash out 400mg of moxifloxacin was taken and then after the final 8 day wash out 2 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment DCBA: 400mg of moxifloxacin was administered orally on Day 1, then an 8 day wash out placebo was taken, then another 8 day wash out 4 g of zoliflodacin was taken and then after the final 8 day wash out 2 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment DBAC: 400mg of moxifloxacin was administered orally on Day 1, then an 8 day wash out 4 g of zoliflodacin was taken, then another 8 day wash out 2 g of zoliflodacin was taken and then after the final 8 day wash out placebo was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment DACB: 400mg of moxifloxacin was administered orally on Day 1, then an 8 day wash out 2 g of zoliflodacin was taken, then another 8 day wash out placebo was taken and then after the final 8 day wash out 4 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Period Title: First Treatment
STARTED	6	6	6	6	6	6	6	6	6	6	6	6
Received Treatment	6	6	6	6	6	6	6	6	6	6	6	6
COMPLETED	6	6	6	6	6	6	6	6	6	6	6	6
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: First Treatment
STARTED	6	6	6	6	6	6	6	6	6	6	6	6
Received Treatment	6	6	6	6	6	6	6	6	6	6	6	6
COMPLETED	6	6	5	6	5	6	6	6	6	6	6	6
NOT COMPLETED	0	0	1	0	1	0	0	0	0	0	0	0
Period Title: First Treatment
STARTED	6	6	5	6	5	6	6	6	6	6	6	6
Received Treatment	6	6	5	6	5	6	5	6	6	6	6	6
COMPLETED	6	6	5	6	4	6	5	6	6	6	6	4
NOT COMPLETED	0	0	0	0	1	0	1	0	0	0	0	2
Period Title: First Treatment
STARTED	6	6	5	6	4	6	5	6	6	6	6	4
Received Treatment	5	6	5	6	4	6	4	6	6	6	6	4
COMPLETED	5	6	5	6	3	6	4	6	6	6	6	4
NOT COMPLETED	1	0	0	0	1	0	1	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	2g Zoliflodacin, 4g Zoliflodacin, Placebo, 400mg Moxifloxacin	2g Zoliflodacin, Placebo, 400mg Moxifloxacin, 4g Zoliflodacin	2g Zoliflodacin, 400mg Moxifloxacin, 4g Zoliflodacin, Placebo	4g Zoliflodacin, 2g Zoliflodacin, 400mg Moxifloxacin, Placebo	4g Zoliflodacin, 400mg Moxifloxacin, Placebo, 2g Zoliflodacin,	4g Zoliflodacin, Placebo, 2g Zoliflodacin, 400mg Moxifloxacin	Placebo, 400mg Moxifloxacin, 2g Zoliflodacin, 4g Zoliflodacin,	Placebo, 2g Zoliflodacin, 4g Zoliflodacin, 400mg Moxifloxacin	Placebo, 4g Zoliflodacin, 400mg Moxifloxacin, 2g Zoliflodacin	400mg Moxifloxacin, Placebo, 4g Zoliflodacin, 2g Zoliflodacin	400mg Moxifloxacin, 4g Zoliflodacin, 2g Zoliflodacin, Placebo	400mg Moxifloxacin, 2g Zoliflodacin, Placebo, 4g Zoliflodacin	Total
Arm/Group Description	Treatment ABCD: 2 g of zoliflodacin administered orally on Day 1, then an 8 day wash out 4 g of zoliflodacin was taken, then another 8 day wash out placebo was taken and then after the final 8 day wash out 400mg of moxifloxacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment ACDB: 2 g of zoliflodacin administered orally on Day 1, then an 8 day wash out placebo was taken, then another 8 day wash out, 400 mg moxifloxacin was taken and then after the final 8 day wash out 4 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water..	Treatment ADBC: 2 g of zoliflodacin administered orally on Day 1, then an 8 day wash out 400mg of moxifloxacin was taken, then another 8 day wash out 4g of zoliflodacin was taken and then after the final 8 day wash out placebo was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment BADC: 4 g of zoliflodacin administered orally on Day 1, then an 8 day wash out2 g of zoliflodacin was taken, then another 8 day wash out 400mg of moxifloxacin was taken and then after the final 8 day wash out placebo was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment BDCA: 4 g of zoliflodacin administered orally on Day 1, then an 8 day wash out 400mg of moxifloxacin was taken, then another 8 day wash out placebo was taken and then after the final 8 day wash out 2 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment BCAD: 4 g of zoliflodacin administered orally on Day 1, then an 8 day wash out placebo was taken, then another 8 day wash out 2 g of zoliflodacin was taken and then after the final 8 day wash out 400mg of moxifloxacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment CDAB: Placebo administered orally on Day 1, then an 8 day wash out 400mg of moxifloxacin was taken, then another 8 day wash out 2 g of zoliflodacin was taken and then after the final 8 day wash out4 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment CABD: Placebo administered orally on Day 1, then an 8 day wash out 2 g of zoliflodacin was taken, then another 8 day wash out 4 g of zoliflodacin was taken and then after the final 8 day wash out 400mg of moxifloxacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment CBDA: Placebo administered orally on Day 1, then an 8 day wash out 4 g of zoliflodacin was taken, then another 8 day wash out 400mg of moxifloxacin was taken and then after the final 8 day wash out 2 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment DCBA: 400mg of moxifloxacin was administered orally on Day 1, then an 8 day wash out placebo was taken, then another 8 day wash out 4 g of zoliflodacin was taken and then after the final 8 day wash out 2 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment DBAC: 400mg of moxifloxacin was administered orally on Day 1, then an 8 day wash out 4 g of zoliflodacin was taken, then another 8 day wash out 2 g of zoliflodacin was taken and then after the final 8 day wash out placebo was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Treatment DACB: 400mg of moxifloxacin was administered orally on Day 1, then an 8 day wash out 2 g of zoliflodacin was taken, then another 8 day wash out placebo was taken and then after the final 8 day wash out 4 g of zoliflodacin was taken. AZD0914: Spiropyrimidinetrione antibacterial drug, Powder was reconstituted in 60 mL of water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin was taken, approximately 60 mL of water was added and consumed by the subject to chase the initial dose. Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose. Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.	Total of all reporting groups
Overall Participants	6	6	6	6	6	6	6	6	6	6	6	6	72
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	72 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.8 (4.4)	29.7 (4.7)	32.5 (4.7)	36.3 (7.4)	30.0 (7.3)	32.5 (8.1)	31.7 (9.4)	34.2 (5.5)	28.7 (4.5)	30.8 (8.9)	31.2 (7.1)	29.0 (6.8)	31.7 (6.6)
Sex: Female, Male (Count of Participants)
Female	2 33.3%	3 50%	2 33.3%	4 66.7%	1 16.7%	4 66.7%	1 16.7%	3 50%	1 16.7%	2 33.3%	1 16.7%	2 33.3%	26 36.1%
Male	4 66.7%	3 50%	4 66.7%	2 33.3%	5 83.3%	2 33.3%	5 83.3%	3 50%	5 83.3%	4 66.7%	5 83.3%	4 66.7%	46 63.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%	1 16.7%	0 0%	0 0%	1 16.7%	2 33.3%	0 0%	2 33.3%	0 0%	0 0%	0 0%	3 50%	10 13.9%
Not Hispanic or Latino	5 83.3%	5 83.3%	6 100%	6 100%	5 83.3%	4 66.7%	6 100%	4 66.7%	6 100%	6 100%	6 100%	3 50%	62 86.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	1 16.7%	3 4.2%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 66.7%	3 50%	4 66.7%	3 50%	1 16.7%	2 33.3%	4 66.7%	3 50%	2 33.3%	4 66.7%	3 50%	2 33.3%	35 48.6%
White	2 33.3%	3 50%	2 33.3%	3 50%	4 66.7%	4 66.7%	2 33.3%	2 33.3%	4 66.7%	2 33.3%	3 50%	3 50%	34 47.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	6 100%	72 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	23.60 (3.20)	23.98 (2.78)	24.48 (2.76)	24.57 (3.28)	26.10 (2.50)	25.07 (3.48)	26.80 (1.58)	25.67 (2.43)	23.43 (3.72)	26.30 (1.68)	25.35 (3.71)	25.03 (2.83)	25.03 (2.87)
Weight (kiliograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kiliograms]	71.38 (11.89)	68.05 (11.16)	72.65 (14.07)	70.05 (14.31)	80.28 (13.93)	73.63 (14.97)	80.63 (7.84)	75.40 (8.74)	75.57 (17.40)	78.88 (10.18)	77.02 (10.28)	70.85 (14.62)	74.53 (12.37)

Outcome Measures

1. Primary Outcome

Title	The One-sided 95% Confidence Interval (CI) for the Largest Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin
Description	Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline QTcF intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.
Time Frame	Baseline, 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose after 2 and 4 g zolifloadacin

Outcome Measure Data

Analysis Population Description

The analysis population sample size is equal to the number of subjects in the Holter ECG Analysis Population who received a dose of zoliflodacin or a dose of placebo.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of dosing period.	4 g of zoliflodacin administered orally on Day 1 of dosing period.	Placebo was administered orally on Day 1 of dosing period.
Measure Participants	68	66	69
0.5 hour post dose	-3.2	-1.0	-2.1
1 hour post dose	-1.9	0.1	-2.3
2 hour post dose	-2.3	0.1	-2.2
3 hour post dose	-1.6	0.1	-2.6
4 hour post dose	-2.4	0.1	-3.3
6 hour post dose	-2.0	-0.7	-2.3
8 hour post dose	-5.6	-4.7	-4.4
12 hour post dose	-2.8	-0.4	-2.2
24 hour post dose	-2.9	-0.3	-2.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 2 g dose causes a prolongation of the QTcF interval 0.5 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms). Power Calculation: Enrollment of 72 subjects would provide at least 84% power to conclude a negative effect, given that up to 16 subjects may withdraw early prior to beginning to replace subjects (at least 56 subjects evaluable), and assuming a standard deviation of ΔΔQTcF of 7 msec and an underlying effect of 5 msec.
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern. Statistically, the test of prolongation is equivalent to a non-inferiority test versus placebo by crossover design, with an non-inferiority margin of 10 ms.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	-0.99
	Confidence Interval	(1-Sided) 95%; to 0.635
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 2 g dose causes a prolongation of the QTcF interval 1 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	0.59
	Confidence Interval	(1-Sided) 95%; to 2.200
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 2 g dose causes a prolongation of the QTcF interval 2 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	0.17
	Confidence Interval	(1-Sided) 95%; to 1.795
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 2 g dose causes a prolongation of the QTcF interval 3 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	1.42
	Confidence Interval	(1-Sided) 95%; to 3.044
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 2 g dose causes a prolongation of the QTcF interval 4 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	1.17
	Confidence Interval	(1-Sided) 95%; to 2.792
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 2 g dose causes a prolongation of the QTcF interval 6 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	0.45
	Confidence Interval	(1-Sided) 95%; to 2.074
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 2 g dose causes a prolongation of the QTcF interval 8 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	-0.83
	Confidence Interval	(1-Sided) 95%; to 0.790
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 2 g dose causes a prolongation of the QTcF interval 12 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	0.03
	Confidence Interval	(1-Sided) 95%; to 1.650
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 2 g dose causes a prolongation of the QTcF interval 24 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	-0.53
	Confidence Interval	(1-Sided) 95%; to 1.131
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	4 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 4 g dose causes a prolongation of the QTcF interval 0.5 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	1.17
	Confidence Interval	(1-Sided) 95%; to 2.815
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	4 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 4 g dose causes a prolongation of the QTcF interval 1 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	2.36
	Confidence Interval	(1-Sided) 95%; to 3.997
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	4 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 4 g dose causes a prolongation of the QTcF interval 2 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	2.18
	Confidence Interval	(1-Sided) 95%; to 3.812
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	4 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 4 g dose causes a prolongation of the QTcF interval 3 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	2.59
	Confidence Interval	(1-Sided) 95%; to 4.228
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	4 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 4 g dose causes a prolongation of the QTcF interval 4 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	3.04
	Confidence Interval	(1-Sided) 95%; to 4.674
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	4 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 4 g dose causes a prolongation of the QTcF interval 6 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	1.63
	Confidence Interval	(1-Sided) 95%; to 3.259
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	4 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 4 g dose causes a prolongation of the QTcF interval 8 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	-0.07
	Confidence Interval	(1-Sided) 95%; to 1.566
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	4 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 4 g dose causes a prolongation of the QTcF interval 12 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	1.82
	Confidence Interval	(1-Sided) 95%; to 3.459
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	4 g of Zoliflodacin, Placebo
	Comments	Null Hypothesis: Zoliflodacin administered at a 4 g dose causes a prolongation of the QTcF interval 24 h post-dose that exceeds the criteria in the ICH Guidance E14 (5 ms).
	Type of Statistical Test	Non-Inferiority
	Comments	Per ICH E14, an increase in the QTcF interval of 5 ms, as evidenced by the upper bound of a 95% one-sided confidence interval above 0.10, is the threshold for regulatory concern.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	1.72
	Confidence Interval	(1-Sided) 95%; to 3.415
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin
Description	Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline heart rate by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

The analysis population sample size is equal to the number of subjects in the Holter ECG Analysis Population who received both a dose of zoliflodacin and a dose of placebo.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of dosing period.	4 g of zoliflodacin administered orally on Day 1 of dosing period.	Placebo was administered orally on Day 1 of dosing period.
Measure Participants	68	66	69
0.5 hour post dose	0.4	2.2	0.1
1 hour post dose	1.6	2.3	-0.6
2 hour post dose	1.0	3.6	0.1
3 hour post dose	2.2	4.5	0.7
4 hour post dose	1.6	3.7	0.00
6 hour post dose	9.4	10.0	7.8
8 hour post dose	8.7	8.3	5.8
12 hour post dose	10.6	10.4	9.7
24 hour post dose	2.5	2.8	3.4

3. Secondary Outcome

Title	Time-matched, Placebo-corrected, Baseline-adjusted, the Time From the Onset of the P Wave to the Start of the QRS Complex (PR Interval) Following Administration of Zoliflodacin
Description	Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline PR intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

The analysis population sample size is equal to the number of subjects in the Holter ECG Analysis Population who received both a dose of zoliflodacin and a dose of placebo.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of dosing period.	4 g of zoliflodacin administered orally on Day 1 of dosing period.	Placebo was administered orally on Day 1 of dosing period.
Measure Participants	68	66	69
0.5 hour post dose	-0.7	-1.1	-0.3
1 hour post dose	-0.9	-2.3	0.2
2 hour post dose	-1.6	-1.8	-0.2
3 hour post dose	-2.6	-2.9	-1.1
4 hour post dose	-2.8	-3.2	-0.6
6 hour post dose	-3.6	-3.9	-1.8
8 hour post dose	-5.7	-5.4	-5.3
12 hour post dose	-3.0	-3.5	-4.3
24 hour post dose	-1.7	-0.8	-0.7

4. Secondary Outcome

Title	Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin
Description	Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline RR intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

The analysis population sample size is equal to the number of subjects in the Holter ECG Analysis Population who received both a dose of zoliflodacin and a dose of placebo.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of dosing period.	4 g of zoliflodacin administered orally on Day 1 of dosing period.	Placebo was administered orally on Day 1 of dosing period.
Measure Participants	68	66	69
0.5 hour post dose	-5.8	-33.5	-1.2
1 hour post dose	-22.6	-35.0	9.7
2 hour post dose	-13.8	-51.0	3.0
3 hour post dose	-32.0	-63.1	-10.1
4 hour post dose	-23.3	-47.6	-0.7
6 hour post dose	-127.1	-133.0	-113.7
8 hour post dose	-120.2	-111.0	-87.5
12 hour post dose	-141.2	-139.8	-140.5
24 hour post dose	-37.4	-41.2	-50.2

5. Secondary Outcome

Title	Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin
Description	Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline QRS durations by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

The analysis population sample size is equal to the number of subjects in the Holter ECG Analysis Population who received both a dose of zoliflodacin and a dose of placebo.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of dosing period.	4 g of zoliflodacin administered orally on Day 1 of dosing period.	Placebo was administered orally on Day 1 of dosing period.
Measure Participants	68	66	69
0.5 hour post dose	-0.3	-0.1	-0.3
1 hour post dose	-0.5	0.1	0.0
2 hour post dose	-0.6	-0.5	0.0
3 hour post dose	-0.4	-0.4	-0.1
4 hour post dose	-0.5	-0.2	-0.1
6 hour post dose	0.1	0.1	0.8
8 hour post dose	-0.7	-0.7	-0.3
12 hour post dose	-0.4	-0.5	-0.3
24 hour post dose	-0.5	-0.2	-0.4

6. Secondary Outcome

Title	The One-sided 95% Confidence Interval (CI) of the Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) After a Single Dose of Moxifloxacin
Description	Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline QTcF intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.
Time Frame	Baseline, 1 h, 2 h, 3 h, and 4 h post-dose

Outcome Measure Data

Analysis Population Description

Any participants who received a dose of moxifloxacin and placebo and had post dose assessments is counted in the population.

Arm/Group Title	400 mg of Moxifloxacin	Placebo
Arm/Group Description	400 mg of moxifloxacin administered orally on Day 1 of dosing period.	Placebo administered orally on Day 1 of dosing period.
Measure Participants	70	69
1 hour post dose	7.9	-2.3
2 hour post dose	8.5	-2.2
3 hour post dose	8.0	-2.6
4 hour post dose	7.2	-3.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, 4 g of Zoliflodacin
	Comments	Null Hypothesis: The trial does not have the sensitivity to detect an effect on QTcF of regulatory concern, as produced by 400 mg moxifloxacin 1 h after dose.
	Type of Statistical Test	Non-Inferiority
	Comments	According to ICH E14, "the positive control should have an effect on the mean QT/QTc interval of about 5 ms." Comparison of the lower bound of the confidence interval to 5 ms for a 400 mg dose of moxifloxacin is standard practice for demonstrating assay sensitivity in thorough QT studies.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	10.19
	Confidence Interval	(1-Sided) 98.75%; 8.257 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, 4 g of Zoliflodacin
	Comments	Null Hypothesis: The trial does not have the sensitivity to detect an effect on QTcF of regulatory concern, as produced by 400 mg moxifloxacin 2 h after dose.
	Type of Statistical Test	Non-Inferiority
	Comments	According to ICH E14, "the positive control should have an effect on the mean QT/QTc interval of about 5 ms." Comparison of the lower bound of the confidence interval to 5 ms for a 400 mg dose of moxifloxacin is standard practice for demonstrating assay sensitivity in thorough QT studies.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	10.79
	Confidence Interval	(1-Sided) 98.75%; 8.860 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, 4 g of Zoliflodacin
	Comments	Null Hypothesis: The trial does not have the sensitivity to detect an effect on QTcF of regulatory concern, as produced by 400 mg moxifloxacin 3 h after dose.
	Type of Statistical Test	Non-Inferiority
	Comments	According to ICH E14, "the positive control should have an effect on the mean QT/QTc interval of about 5 ms." Comparison of the lower bound of the confidence interval to 5 ms for a 400 mg dose of moxifloxacin is standard practice for demonstrating assay sensitivity in thorough QT studies.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	10.62
	Confidence Interval	(1-Sided) 98.75%; 8.683 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	2 g of Zoliflodacin, 4 g of Zoliflodacin
	Comments	Null Hypothesis: The trial does not have the sensitivity to detect an effect on QTcF of regulatory concern, as produced by 400 mg moxifloxacin 4 h after dose.
	Type of Statistical Test	Non-Inferiority
	Comments	According to ICH E14, "the positive control should have an effect on the mean QT/QTc interval of about 5 ms." Comparison of the lower bound of the confidence interval to 5 ms for a 400 mg dose of moxifloxacin is standard practice for demonstrating assay sensitivity in thorough QT studies.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Double Delta Value
	Estimated Value	10.63
	Confidence Interval	(1-Sided) 98.75%; 8.698 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin
Description	Categorical T-wave morphology analysis was collected in three ECG replicates at each timepoint (Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose). Abnormalities present in any one or more of the baseline timepoint replicate ECGs recorded for a particular period was considered to be present at baseline for post-dose ECGs from that specific period. If a subject had an ECG morphological abnormality in more than one replicate ECG of a study timepoint, the subject was counted only once for that timepoint. Flat is defined as T amplitude <1 mm (either positive or negative) including flat isoelectric line and Biphasic is defined as T-wave that contains a second component with an opposite phase that was at least 0.1 millivolts (mV) deep (both positive and negative/positive and polyphasic T-waves included).
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose assessments.

Arm/Group Title	Placebo	2 g of Zoliflodacin	4 g of Zoliflodacin	400 mg of Moxifloxacin
Arm/Group Description	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	68	66	70
0.5 h post dose: T wave: Abnormal, Biphasic	0 0%	0 0%	0 0%	0 0%
0.5 h post dose: T wave: Abnormal, Flat	0 0%	0 0%	0 0%	0 0%
0.5 h post: T wave:Abnormal, Inverted, Asymmetric	0 0%	0 0%	0 0%	0 0%
1 h post dose: T wave: Abnormal, Biphasic	0 0%	0 0%	0 0%	0 0%
1 h post dose: T wave: Abnormal, Flat	0 0%	0 0%	0 0%	0 0%
1 h post: T wave: Abnormal, Inverted, Asymmetric	0 0%	0 0%	0 0%	0 0%
2 h post dose: T wave: Abnormal, Biphasic	0 0%	0 0%	0 0%	0 0%
2 h post dose: T wave: Abnormal, Flat	0 0%	0 0%	2 33.3%	1 16.7%
2 h post: T wave: Abnormal, Inverted, Asymmetric	0 0%	0 0%	0 0%	0 0%
3 h post dose: T wave: Abnormal, Biphasic	0 0%	0 0%	0 0%	0 0%
3 h post dose: T wave: Abnormal, Flat	0 0%	0 0%	2 33.3%	0 0%
3 h post:T wave: Abnormal, Inverted, Asymmetric	0 0%	0 0%	1 16.7%	0 0%
4 h post dose: T wave: Abnormal, Biphasic	0 0%	0 0%	0 0%	0 0%
4 h post dose: T wave: Abnormal, Flat	0 0%	0 0%	2 33.3%	0 0%
4 h post:T wave: Abnormal, Inverted, Asymmetric	0 0%	0 0%	1 16.7%	0 0%
6 h post dose: T wave: Abnormal, Biphasic	0 0%	0 0%	1 16.7%	0 0%
6 h post dose: T wave: Abnormal, Flat	6 100%	4 66.7%	4 66.7%	5 83.3%
6 h post:T wave: Abnormal, Inverted, Asymmetric	2 33.3%	0 0%	1 16.7%	1 16.7%
8 h post dose: T wave: Abnormal, Biphasic	0 0%	0 0%	1 16.7%	0 0%
8 h post dose: T wave: Abnormal, Flat	3 50%	1 16.7%	2 33.3%	1 16.7%
8 h post:T wave: Abnormal, Inverted, Asymmetric	0 0%	0 0%	1 16.7%	0 0%
12 h post dose: T wave: Abnormal, Biphasic	0 0%	0 0%	1 16.7%	0 0%
12 h post dose: T wave: Abnormal, Flat	1 16.7%	4 66.7%	2 33.3%	1 16.7%
12 h post:T wave: Abnormal, Inverted, Asymmetric	0 0%	1 16.7%	1 16.7%	0 0%
24 h post dose: T wave: Abnormal, Biphasic	0 0%	0 0%	1 16.7%	0 0%
24 h post dose: T wave: Abnormal, Flat	0 0%	0 0%	0 0%	1 16.7%
24 h post:T wave: Abnormal, Inverted, Asymmetric	0 0%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of Zoliflodacin
Description	Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations computed from concentrations that were measured using a validated HPLC-MS/MS method. Pharmacokinetic (PK) parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.
Measure Participants	69	67
Mean (Standard Deviation) [ng/mL]	12120 (2985)	20350 (8682)

9. Secondary Outcome

Title	Time of Maximum Observed Concentration (Tmax) of Zoliflodacin
Description	Tmax is defined as the time at which the maximum concentration (Cmax) occurs in plasma computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.
Measure Participants	69	67
Mean (Standard Deviation) [hour]	2.90 (1.08)	3.03 (2.05)

10. Secondary Outcome

Title	Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0 - Infinity)) for Zoliflodacin
Description	AUC(0 - infinity) was defined as the total area under the concentration-time curve from dosing (time 0) taken to the limit as the end time becomes arbitrarily large. AUC(0 - infinity) was calculated by adding AUC(0-last) to an extrapolated value equal to the last measured concentration greater than the lower limit of quantification of the bioanalytical assay divided by the terminal phase elimination rate constant (Ke) computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.
Measure Participants	69	67
Mean (Standard Deviation) [h x ng/mL]	108300 (32980)	181400 (52890)

11. Secondary Outcome

Title	Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin
Description	AUC(0-last) was defined as the area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.
Measure Participants	69	67
Mean (Standard Deviation) [h*ng/mL]	102700 (28580)	177300 (52370)

12. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) of Zoliflodacin
Description	Apparent volume of distribution during terminal phase (Vz/F) after non-intravenous administration was calculated as (CL/F)/ Ke computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.
Measure Participants	50	42
Mean (Standard Deviation) [Liter]	160.55 (50.46)	204.29 (55.13)

13. Secondary Outcome

Title	Apparent Oral Clearance (CL/F) of Zoliflodacin
Description	Apparent oral clearance (CL/F) computed as Dose/Area under the curve (AUC) from time zero to infinity (0-infinity) computed from concentrations that were measured using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.
Measure Participants	50	42
Mean (Standard Deviation) [Liter/hour]	20.08 (5.74)	23.77 (6.34)

14. Secondary Outcome

Title	Elimination Rate Constant (Ke) of Zoliflodacin
Description	The terminal phase elimination rate constant (Ke) was defined as the first-order rate constant describing the rate of decrease of drug concentration in the terminal phase (defined as the terminal region of the PK curve where drug concentration follows first-order elimination kinetics) computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.
Measure Participants	50	42
Mean (Standard Deviation) [1/hour]	0.1267 (0.01590)	0.1174 (0.01467)

15. Secondary Outcome

Title	Terminal Elimination Half-life (t1/2) of Zoliflodacin
Description	The apparent terminal elimination half-life (t1/2) was defined as the time required for the drug concentration to decrease by a factor of one-half in the terminal phase computed from concentrations that were measured using a validated HPLC-MS/MS method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.
Measure Participants	50	42
Mean (Standard Deviation) [Hour]	5.55 (0.67)	5.99 (0.71)

16. Secondary Outcome

Title	Relationship Between Plasma Concentrations of Zoliflodacin and Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin
Description	One-sided 95% confidence intervals of population mean QTcF time-matched, placebo-corrected, baseline-adjusted mean QTcF interval at plasma concentration corresponding to the observed geometric mean Cmax for 2 g and 4 g doses of zoliflodacin were computed using a linear mixed effect model with PK and concentration data collected at baseline and intervals post-dose.
Time Frame	Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.
Measure Participants	67	65
Mean (95% Confidence Interval) [milliseconds (msec)]	1.5	3.0

17. Secondary Outcome

Title	Number of Participants With Treatment-emergent Serious Adverse Events Following Administration of Zoliflodacin and Moxifloxacin
Description	Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect.
Time Frame	From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	71
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events Following Administration of Study Product
Description	Adverse events are defined as any untoward medical occurrence regardless of its causal relationship to the study treatment.
Time Frame	From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	71
Count of Participants [Participants]	38 633.3%	46 766.7%	35 583.3%	41 683.3%

19. Secondary Outcome

Title	Changes From Baseline for Blood Pressure - Systolic
Description	Change from baseline in systolic blood pressure was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.
Time Frame	From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	71
1 hour post dose	0.8 (7.3)	1.3 (7.9)	0.8 (7.6)	0.4 (7.8)
2 hour post dose	0.4 (8.0)	-0.3 (7.6)	1.0 (8.6)	-0.5 (6.8)
4 hour post dose	0.1 (7.1)	-0.9 (7.5)	1.0 (7.6)	-1.7 (7.7)
24 hour post dose	0.0 (8.2)	-0.4 (7.8)	1.1 (7.3)	0.5 (6.9)
Follow up	3.5 (8.2)	2.3 (6.9)	3.7 (9.2)	5.0 (8.4)

20. Secondary Outcome

Title	Changes From Baseline for Blood Pressure - Diastolic
Description	Change from baseline in diastolic blood pressure was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.
Time Frame	From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	71
1 hour post dose	0.3 (5.3)	0.3 (4.8)	0.8 (6.1)	1.5 (5.3)
2 hour post dose	-0.4 (6.0)	-0.9 (5.1)	0.6 (6.7)	1.2 (5.5)
4 hour post dose	-0.4 (4.9)	-2.3 (5.3)	1.1 (5.7)	-0.1 (5.5)
24 hour post dose	0.2 (5.3)	-0.5 (5.7)	1.4 (5.4)	1.1 (5.5)
Follow up	2.2 (5.3)	0.5 (5.5)	2.7 (6.7)	3.8 (7.2)

21. Secondary Outcome

Title	Changes From Baseline for Pulse Rate
Description	Change from baseline in pulse rate was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.
Time Frame	From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	71
1 hour post dose	5.2 (8.3)	5.7 (7.8)	2.8 (8.1)	6.9 (6.8)
2 hour post dose	3.9 (7.8)	6.5 (8.0)	3.8 (7.5)	5.5 (5.8)
4 hour post dose	5.4 (8.5)	5.8 (8.3)	3.0 (9.6)	5.2 (8.2)
24 hour post dose	4.9 (7.7)	5.2 (7.3)	5.4 (8.4)	6.3 (8.1)
Follow up	2.0 (8.7)	2.8 (7.7)	2.0 (10.3)	4.2 (7.2)

22. Secondary Outcome

Title	Changes From Baseline for Respiratory Rate
Description	Change from baseline in respiratory rate was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.
Time Frame	From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	71
1 hour post dose	0.8 (3.1)	1.1 (2.9)	1.0 (2.8)	0.4 (3.0)
2 hour post dose	0.4 (3.2)	0.7 (2.9)	-0.3 (3.0)	0.0 (3.0)
4 hour post dose	0.8 (3.6)	1.3 (3.3)	-0.2 (2.7)	0.1 (3.1)
24 hour post dose	0.9 (3.1)	1.0 (2.9)	0.6 (2.7)	0.5 (3.0)
Follow up	0.6 (3.1)	1.3 (3.3)	0.2 (3.0)	0.6 (3.6)

23. Secondary Outcome

Title	Changes From Baseline for Temperature
Description	Change from baseline for temperature was calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h and 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.
Time Frame	From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	71
1 hour post dose	0.08 (0.26)	0.03 (0.25)	0.03 (0.27)	0.05 (0.31)
2 hour post dose	0.10 (0.21)	0.06 (0.22)	0.09 (0.24)	0.11 (0.23)
4 hour post dose	0.08 (0.23)	0.05 (0.27)	0.09 (0.24)	0.13 (0.26)
24 hour post dose	0.09 (0.27)	0.06 (0.27)	0.04 (0.27)	0.10 (0.26)
Follow up	0.05 (0.28)	-0.02 (0.31)	0.00 (0.28)	0.05 (0.29)

24. Secondary Outcome

Title	Changes From Baseline for White Blood Cells With Differentials
Description	Change from baseline calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Hematology parameters included white blood cell count, and differential (absolute counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils).
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
Leukocytes: 24 hour post dose	-246.4 (1031.5)	-129.9 (1249.6)	-64.3 (1130.2)	-282.9 (1075.4)
Leukocytes: Follow up	-273.5 (1253.1)	140.3 (1486.1)	35.8 (1153.9)	-84.1 (1477.6)
Neutrophils: 24 hour post dose	-248.0 (667.7)	-39.6 (955.3)	-54.3 (1036.5)	-351.3 (1008.5)
Neutrophils: Follow up	-272.2 (945.4)	220.4 (1136.7)	-36.1 (986.4)	-59.2 (1216.6)
Lymphocytes: 24 hour post dose	3.4 (583.2)	-77.9 (499.6)	-1.9 (549.7)	79.4 (556.9)
Lymphocytes: Follow up	-19.6 (497.9)	-74.1 (530.5)	96.9 (482.9)	-33.7 (625.8)
Monocytes: 24 hour post dose	-7.8 (118.2)	-13.9 (125.3)	-10.6 (123.7)	-16.1 (114.8)
Monocytes: Follow up	4.6 (118.8)	-7.6 (158.7)	-25.4 (141.0)	5.2 (138.9)
Eosinophils: 24 hour post dose	9.4 (65.1)	4.0 (71.0)	6.0 (72.8)	8.2 (64.7)
Eosinophils: Follow up	12.9 (80.9)	2.2 (83.9)	0.7 (69.7)	2.3 (61.2)
Basophils: 24 hour post dose	-3.4 (13.8)	-2.5 (13.3)	-3.3 (13.5)	-3.1 (14.4)
Basophils: Follow up	0.6 (15.7)	-0.5 (14.9)	-0.2 (10.7)	1.4 (14.7)

25. Secondary Outcome

Title	Changes From Baseline for Hemoglobin
Description	Change from baseline for hemoglobin is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
Hemoglobin: 24 hour post dose	0.15 (0.71)	0.01 (0.65)	0.04 (0.67)	-0.06 (0.68)
Hemoglobin: Follow up	-0.01 (0.72)	-0.23 (0.68)	-0.06 (0.64)	-0.13 (0.70)

26. Secondary Outcome

Title	Changes From Baseline for Hematocrit
Description	Change from baseline for hematocrit is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
Hematocrit: 24 hour post dose	0.39 (2.04)	-0.10 (2.02)	0.08 (2.08)	-0.26 (2.13)
Hematocrit: Follow up	-0.03 (2.26)	-0.69 (2.15)	-0.10 (1.90)	-0.33 (2.19)

27. Secondary Outcome

Title	Changes From Baseline for Erythrocytes
Description	Change from baseline for erythrocytes is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
Erythrocytes: 24 hour post dose	0.050 (0.243)	-0.008 (0.228)	-0.002 (0.233)	-0.031 (0.253)
Erythrocytes: Follow up	-0.005 (0.280)	-0.088 (0.249)	-0.029 (0.212)	-0.053 (0.248)

28. Secondary Outcome

Title	Changes From Baseline for Platelets
Description	Change from baseline for platelets is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product for that dosing period and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
Platelets: 24 hour post dose	-8.2 (25.8)	-10.3 (26.9)	-10.5 (24.4)	-15.4 (23.3)
Platelets: Follow up	1.7 (27.8)	2.9 (30.4)	6.2 (30.3)	-3.8 (29.3)

29. Secondary Outcome

Title	Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate
Description	Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included sodium, potassium. chloride and bicarbonate.
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product for that dosing period and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
Sodium: 24 hour post dose	0.2 (1.9)	-0.1 (1.9)	0.6 (1.9)	0.7 (1.9)
Sodium: Follow up	0.1 (2.3)	-0.3 (1.7)	0.6 (1.8)	0.2 (1.9)
Potassium: 24 hour post dose	0.26 (0.41)	0.25 (0.39)	0.17 (0.41)	0.11 (0.36)
Potassium: Follow up	0.01 (0.33)	-0.02 (0.45)	0.01 (0.40)	-0.01 (0.41)
Chloride: 24 hour post dose	1.3 (2.0)	1.0 (1.9)	1.4 (2.0)	1.4 (2.0)
Chloride: Follow up	0.3 (2.1)	-0.3 (2.3)	0.5 (1.7)	0.1 (2.1)
Bicarbonate: 24 hour post dose	0.2 (2.4)	0.1 (1.8)	0.6 (1.9)	0.4 (2.1)
Bicarbonate: Follow up	-0.2 (2.2)	-0.3 (2.2)	0.3 (2.1)	-0.1 (2.2)

30. Secondary Outcome

Title	Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin
Description	Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included magnesium, glucose (fasting), BUN, creatinine, total bilirubin, direct bilirubin
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product for that dosing period and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
Magnesium: 24 hour post dose	0.05 (0.13)	0.03 (0.13)	0.02 (0.14)	0.01 (0.14)
Magnesium: Follow up	0.04 (0.12)	0.00 (0.13)	0.02 (0.13)	0.01 (0.12)
Glucose (fasting): 24 hour post dose	4.6 (7.8)	6.4 (9.7)	4.2 (8.3)	3.2 (7.4)
Glucose (fasting): Follow up	-1.2 (8.7)	1.5 (9.8)	-0.6 (8.9)	1.0 (9.5)
BUN: 24 hour post dose	2.1 (3.2)	1.6 (3.0)	1.4 (2.9)	2.5 (3.4)
BUN: Follow up	0.7 (3.3)	0.0 (2.9)	0.1 (3.0)	-0.2 (4.0)
Creatinine: 24 hour post dose	0.082 (0.082)	0.086 (0.072)	0.003 (0.059)	0.059 (0.078)
Creatinine: Follow up	0.034 (0.102)	-0.011 (0.089)	0.006 (0.071)	-0.007 (0.087)
Total Bilirubin: 24 hour post dose	0.07 (0.25)	0.14 (0.23)	-0.01 (0.24)	-0.04 (0.20)
Total Bilirubin: Follow up	0.01 (0.21)	-0.04 (0.14)	-0.01 (0.17)	-0.02 (0.16)
Direct Bilirubin: 24 hour post dose	0.00 (0.07)	0.02 (0.06)	0.00 (0.06)	-0.01 (0.05)
Direct Bilirubin: Follow up	-0.01 (0.06)	0.00 (0.05)	0.01 (0.06)	-0.01 (0.05)

31. Secondary Outcome

Title	Changes From Baseline for Total Protein and Albumin
Description	Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included total protein and albumin.
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product for that dosing period and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
Total Protein: 24 hour post dose	-0.42 (0.45)	-0.42 (0.39)	-0.45 (0.43)	-0.45 (0.38)
Total Protein: Follow up	-0.01 (0.49)	-0.06 (0.39)	-0.01 (0.40)	0.03 (0.41)
Albumin: 24 hour post dose	-0.28 (0.25)	-0.30 (0.23)	-0.30 (0.24)	-0.32 (0.23)
Albumin: Follow up	0.00 (0.28)	-0.05 (0.22)	0.01 (0.23)	0.02 (0.23)

32. Secondary Outcome

Title	Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP)
Description	Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included AST, ALT and AP.
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product for that dosing period and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
AST: 24 hour post dose	-2.9 (3.0)	-2.7 (5.6)	-2.7 (3.5)	-2.8 (4.4)
AST: Follow up	0.1 (5.6)	0.0 (4.0)	-0.5 (3.3)	0.6 (5.9)
ALT: 24 hour post dose	-2.2 (4.1)	-1.7 (2.7)	-1.7 (4.0)	-1.4 (3.8)
ALT: Follow up	-0.7 (6.9)	1.6 (7.5)	-0.6 (4.2)	0.8 (4.3)
AP: 24 hour post dose	-5.2 (6.3)	-3.9 (4.6)	-4.1 (4.9)	-4.2 (5.8)
AP: Follow up	-1.7 (8.1)	-0.4 (7.0)	-0.7 (4.8)	1.0 (7.0)

33. Secondary Outcome

Title	Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated
Description	Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit.
Time Frame	Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
GFR: 24 hour post dose	-10.4 (11.1)	-9.5 (8.1)	-0.1 (8.1)	-6.2 (10.3)
GFR: Follow up	-5.3 (16.3)	1.8 (11.0)	-0.7 (8.5)	1.5 (11.9)

34. Secondary Outcome

Title	Occurrence of Urinalysis Adverse Events Following Administration of Study Product
Description	Urine for the clinical laboratory test was collected on Day -1, 24 hour post dose and the check in for the following dosing period. The results for glucose dipstick, protein dipstick and occult blood - dipstick were reported in categorical results. The possibilities were negative, trace, 1+, 2+, and 3+. If the dipsticks were 1+ or greater, microscopic evaluations were performed for erythrocytes, leukocytes and bacteria. For microscopic results to be deemed abnormal, the results must be reported 6 or greater per high power field.
Time Frame	From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose laboratory assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	70
Glucose dipstick: 24 hour post dose	0 0%	0 0%	0 0%	0 0%
Glucose dipstick: Follow up	0 0%	0 0%	0 0%	0 0%
Protein dipstick: 24 hour post dose	1 16.7%	1 16.7%	0 0%	0 0%
Protein dipstick: Follow up	2 33.3%	0 0%	0 0%	1 16.7%
Occult blood dipstick: 24 hour post dose	1 16.7%	4 66.7%	5 83.3%	3 50%
Occult blood dipstick: Follow up	4 66.7%	2 33.3%	0 0%	1 16.7%
Erythrocytes microscopic: 24 hour post dose	2 33.3%	2 33.3%	2 33.3%	3 50%
Erythrocytes microscopic: Follow up	3 50%	1 16.7%	2 33.3%	2 33.3%
Leukocytes microscopic: 24 hour post dose	0 0%	1 16.7%	0 0%	2 33.3%
Leukocytes microscopic: Follow up	0 0%	0 0%	1 16.7%	0 0%
Bacteria microscopic: 24 hour post dose	0 0%	3 50%	2 33.3%	2 33.3%
Bacteria microscopic: Follow up	2 33.3%	1 16.7%	2 33.3%	0 0%

35. Secondary Outcome

Title	Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval
Description	Change from baseline in ECG is calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, 24 h after dosing and prior to the next dose (follow up). The following ECG Parameters were analyzed: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex), QRS Duration (Time From the Start of the Q-wave to the End of the S-wave), QT Interval (Interval From Onset of the Q-wave to the End of the T-wave), QTcF Interval (QT Interval Corrected by Fridericia's Formula) and RR Interval (Interval From the Peak of the R Wave of a QRS Complex to the Peak of the R Wave of the Next QRS Complex).
Time Frame	Baseline, 1 h, 2 h, 4h, 24 h post-dose and follow up

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose ECG assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	71
PR Interval: 1 hr post dose	1.2 (8.9)	0.0 (7.7)	1.3 (8.5)	1.3 (11.7)
PR Interval: 2 hr post dose	1.2 (8.3)	-0.7 (7.8)	0.6 (7.6)	0.4 (11.5)
PR Interval: 4 hr post dose	-0.3 (8.0)	-1.4 (8.3)	-0.4 (7.8)	-0.9 (11.6)
PR Interval: 24 hr post dose	1.1 (7.8)	0.7 (7.9)	0.5 (8.2)	2.8 (11.3)
PR Interval: Follow up	-1.2 (8.8)	-1.9 (9.8)	-3.1 (9.9)	-0.9 (13.3)
QRS Duration: 1 hr post dose	-1.8 (4.1)	-0.6 (5.1)	0.4 (5.1)	-0.5 (6.7)
QRS Duration: 2 hr post dose	-1.9 (6.6)	-1.4 (4.9)	-0.7 (5.9)	-1.5 (8.0)
QRS Duration: 4 hr post dose	-2.0 (3.9)	-1.0 (5.2)	-0.7 (5.1)	-1.6 (7.4)
QRS Duration: 24 hr post dose	-2.7 (4.9)	-1.1 (6.8)	-0.9 (5.0)	-1.1 (7.0)
QRS Duration: Follow up	-1.4 (6.0)	0.3 (6.9)	-1.1 (5.3)	-0.2 (8.6)
QT Interval: 1 hr post dose	-3.6 (13.1)	-6.2 (12.2)	-2.5 (11.1)	-1.4 (12.6)
QT Interval: 2 hr post dose	-5.3 (14.6)	-7.6 (15.6)	-3.6 (13.3)	2.3 (16.7)
QT Interval: 4 hr post dose	-5.0 (13.8)	-9.1 (18.3)	-3.8 (14.3)	2.0 (16.1)
QT Interval: 24 hr post dose	-6.8 (12.3)	-7.6 (15.9)	-9.9 (15.1)	-3.7 (14.1)
QT Interval: Follow up	-7.1 (20.7)	-6.6 (21.1)	-8.3 (20.2)	-10.0 (18.4)
QTcF Interval: 1 hr post dose	1.5 (10.8)	0.6 (9.3)	-0.4 (9.2)	9.2 (10.9)
QTcF Interval: 2 hr post dose	0.4 (9.9)	2.0 (10.2)	-2.9 (9.5)	10.6 (11.5)
QTcF Interval: 4 hr post dose	0.7 (10.8)	-1.3 (12.2)	-3.0 (9.9)	8.5 (12.0)
QTcF Interval: 24 hr post dose	1.5 (8.5)	1.9 (9.3)	-3.5 (10.3)	4.1 (11.6)
QTcF Interval: Follow up	-1.4 (12.7)	-0.2 (12.8)	-3.8 (14.4)	-1.4 (14.9)
RR Interval: 1 hr post dose	-34.9 (99.9)	-48.4 (86.0)	-14.1 (80.6)	-74.5 (100.2)
RR Interval: 2 hr post dose	-38.5 (99.7)	-68.7 (82.0)	-3.3 (94.0)	-59.0 (107.3)
RR Interval: 4 hr post dose	-38.8 (94.7)	-54.3 (102.3)	-4.8 (113.1)	-46.6 (114.0)
RR Interval: 24 hr post dose	-57.6 (83.5)	-66.9 (91.3)	-45.9 (106.1)	-56.8 (87.0)
RR Interval: Follow up	-39.6 (112.7)	-45.6 (108.6)	-32.4 (125.5)	-62.1 (103.1)

36. Secondary Outcome

Title	Changes From Baseline in ECG Measures: Ventricular Rate
Description	Change from baseline in ECG Ventricular Rate is calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, 24 h after dosing and prior to the next dose (follow up).
Time Frame	Baseline, 1 h, 2 h, 4h, 24 h post-dose and follow up

Outcome Measure Data

Analysis Population Description

Any participants who received study product and had post dose ECG assessments.

Arm/Group Title	2 g of Zoliflodacin	4 g of Zoliflodacin	Placebo	400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.	Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.	400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
Measure Participants	69	67	70	71
Ventricular Rate: 1 hr post dose	2.4 (6.6)	3.3 (5.3)	0.9 (5.1)	4.7 (6.2)
Ventricular Rate: 2 hr post dose	2.9 (6.8)	4.6 (6.2)	0.4 (6.5)	3.6 (6.8)
Ventricular Rate: 4 hr post dose	2.8 (6.6)	4.1 (7.5)	0.2 (7.3)	2.8 (7.4)
Ventricular Rate: 24 hr post dose	3.9 (5.8)	4.6 (6.4)	2.9 (8.0)	3.5 (5.8)
Ventricular Rate: Follow up	2.8 (8.2)	3.1 (7.3)	1.8 (8.9)	3.9 (7.0)

Adverse Events

Time Frame	Unsolicited adverse events and serious adverse events (SAEs) were collected from study product administration to Day 8 after treatment administration or final visit.
Adverse Event Reporting Description	Treatment emergent adverse events were defined as new events post-dose, or worsening of existing conditions post-dose. The adverse events were captured by changes in laboratory values, vital signs, ECGs and unsolicited adverse events immediately post dose to Day 8 post each treatment administration or early termination, whichever came first.
Arm/Group Title	2 g of Zoliflodacin		4 g of Zoliflodacin		Placebo		400 mg of Moxifloxacin
Arm/Group Description	2 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.		4 g of zoliflodacin administered orally on Day 1 of each dosing period AZD0914: Spiropyrimidinetrione antibacterial drug, powder (zoliflodacin) was reconstituted in 60 mL of water and dosed orally following an overnight fast, after which approximately 60 mL of water was added to the cup and consumed by the subject.		Placebo for zoliflodacin administered orally on Day 1 of each dosing period Placebo: Composed of 4g of the same excipients found in zoliflodacin. Powder was reconstituted in 60 mL of water and dosed orally. After the cup containing 60 mL of placebo was taken, approximately 60 mL of water was consumed by the subject to chase the initial dose.		400 mg of moxifloxacin administered orally on Day 1 of each dosing period Moxifloxacin: Broad-spectrum 8-methoxy fluoroquinolone. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride was administered orally with 120 mL of water.
All Cause Mortality
	2 g of Zoliflodacin		4 g of Zoliflodacin		Placebo		400 mg of Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/67 (0%)		0/70 (0%)		0/71 (0%)
Serious Adverse Events
	2 g of Zoliflodacin		4 g of Zoliflodacin		Placebo		400 mg of Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/67 (0%)		0/70 (0%)		0/71 (0%)
Other (Not Including Serious) Adverse Events
	2 g of Zoliflodacin		4 g of Zoliflodacin		Placebo		400 mg of Moxifloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/69 (55.1%)		46/67 (68.7%)		30/70 (42.9%)		34/71 (47.9%)
Gastrointestinal disorders
DIARRHOEA	0/69 (0%)	0	4/67 (6%)	4	0/70 (0%)	0	0/71 (0%)	0
NAUSEA	2/69 (2.9%)	2	6/67 (9%)	6	1/70 (1.4%)	1	3/71 (4.2%)	3
Investigations
BACTERIAL TEST POSITIVE	2/69 (2.9%)	2	4/67 (6%)	4	5/70 (7.1%)	5	2/71 (2.8%)	2
ELECTROCARDIOGRAM QT PROLONGED	5/69 (7.2%)	8	3/67 (4.5%)	4	2/70 (2.9%)	2	15/71 (21.1%)	15
HAEMOGLOBIN DECREASED	2/69 (2.9%)	2	4/67 (6%)	4	3/70 (4.3%)	3	1/71 (1.4%)	1
HEART RATE DECREASED	13/69 (18.8%)	14	10/67 (14.9%)	12	13/70 (18.6%)	16	11/71 (15.5%)	16
NEUTROPHIL COUNT DECREASED	1/69 (1.4%)	1	4/67 (6%)	4	2/70 (2.9%)	2	1/71 (1.4%)	1
Nervous system disorders
DYSGEUSIA	6/69 (8.7%)	6	5/67 (7.5%)	5	2/70 (2.9%)	2	0/71 (0%)	0
HEADACHE	7/69 (10.1%)	7	12/67 (17.9%)	13	2/70 (2.9%)	2	1/71 (1.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.