Electrocardiogram Repolarisation Abnormality, Gonococcal Infection
Conditions
Keywords
AZD0914, Cardiac, ETX0914, Healthy, Moxifloxacin, Repolarization, Study, TQT, Volunteers, Zoliflodacin
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).
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.
Interventions
DRUGAZD0914
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.
DRUGMoxifloxacin
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.
OTHERPlacebo
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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
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 1572) 3. 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 4. Aged 18 to 45 years inclusive on the day of first dosing 5. Body Mass Index (BMI) \> / = 18.5 and \< / = to 30 kg per m\^2 and weight \> / = 50 kg (110 lbs.) and \< / = 100 kg (220 lbs.) 6. 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). 7. If female, not pregnant, not breast feeding, and not planning to become pregnant during the trial and for 30 days after Final Visit 8. 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. 9. Male subjects agree to refrain from sperm donation for the duration of the trial and for 90 days after Final Visit 10. Laboratory tests are in the normal reference range with acceptable exceptions 11. Vital signs (VS) are within the acceptable range 12. Has adequate venous access for blood collection 13. Urine drug screen is negative for tested substances 14. Urine alcohol test is negative 15. 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 7. 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 20. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| 2g Zoliflodacin, 4g Zoliflodacin, Placebo, 400mg Moxifloxacin 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. | 6 |
| 2g Zoliflodacin, Placebo, 400mg Moxifloxacin, 4g Zoliflodacin 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.. | 6 |
| 2g Zoliflodacin, 400mg Moxifloxacin, 4g Zoliflodacin, Placebo 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. | 6 |
| 4g Zoliflodacin, 2g Zoliflodacin, 400mg Moxifloxacin, Placebo 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. | 6 |
| 4g Zoliflodacin, 400mg Moxifloxacin, Placebo, 2g Zoliflodacin, 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. | 6 |
| 4g Zoliflodacin, Placebo, 2g Zoliflodacin, 400mg Moxifloxacin 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. | 6 |
| Placebo, 400mg Moxifloxacin, 2g Zoliflodacin, 4g Zoliflodacin, 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. | 6 |
| Placebo, 2g Zoliflodacin, 4g Zoliflodacin, 400mg Moxifloxacin 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. | 6 |
| Placebo, 4g Zoliflodacin, 400mg Moxifloxacin, 2g Zoliflodacin 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. | 6 |
| 400mg Moxifloxacin, Placebo, 4g Zoliflodacin, 2g Zoliflodacin 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. | 6 |
| 400mg Moxifloxacin, 4g Zoliflodacin, 2g Zoliflodacin, Placebo 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. | 6 |
| 400mg Moxifloxacin, 2g Zoliflodacin, Placebo, 4g Zoliflodacin 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. | 6 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fourth Treatment | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Fourth Treatment | Protocol Violation | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Second Treatment | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Second Treatment | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Third Treatment | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Third Treatment | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 72 Participants |
| Age, Continuous | 33.8 years STANDARD_DEVIATION 4.4 | 29.7 years STANDARD_DEVIATION 4.7 | 32.5 years STANDARD_DEVIATION 4.7 | 36.3 years STANDARD_DEVIATION 7.4 | 30.0 years STANDARD_DEVIATION 7.3 | 32.5 years STANDARD_DEVIATION 8.1 | 31.7 years STANDARD_DEVIATION 9.4 | 34.2 years STANDARD_DEVIATION 5.5 | 28.7 years STANDARD_DEVIATION 4.5 | 30.8 years STANDARD_DEVIATION 8.9 | 31.2 years STANDARD_DEVIATION 7.1 | 29.0 years STANDARD_DEVIATION 6.8 | 31.7 years STANDARD_DEVIATION 6.6 |
| BMI | 23.60 kg/m^2 STANDARD_DEVIATION 3.2 | 23.98 kg/m^2 STANDARD_DEVIATION 2.78 | 24.48 kg/m^2 STANDARD_DEVIATION 2.76 | 24.57 kg/m^2 STANDARD_DEVIATION 3.28 | 26.10 kg/m^2 STANDARD_DEVIATION 2.5 | 25.07 kg/m^2 STANDARD_DEVIATION 3.48 | 26.80 kg/m^2 STANDARD_DEVIATION 1.58 | 25.67 kg/m^2 STANDARD_DEVIATION 2.43 | 23.43 kg/m^2 STANDARD_DEVIATION 3.72 | 26.30 kg/m^2 STANDARD_DEVIATION 1.68 | 25.35 kg/m^2 STANDARD_DEVIATION 3.71 | 25.03 kg/m^2 STANDARD_DEVIATION 2.83 | 25.03 kg/m^2 STANDARD_DEVIATION 2.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 4 Participants | 6 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 35 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 34 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 72 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 4 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 26 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 5 Participants | 4 Participants | 46 Participants |
| Weight | 71.38 kiliograms STANDARD_DEVIATION 11.89 | 68.05 kiliograms STANDARD_DEVIATION 11.16 | 72.65 kiliograms STANDARD_DEVIATION 14.07 | 70.05 kiliograms STANDARD_DEVIATION 14.31 | 80.28 kiliograms STANDARD_DEVIATION 13.93 | 73.63 kiliograms STANDARD_DEVIATION 14.97 | 80.63 kiliograms STANDARD_DEVIATION 7.84 | 75.40 kiliograms STANDARD_DEVIATION 8.74 | 75.57 kiliograms STANDARD_DEVIATION 17.4 | 78.88 kiliograms STANDARD_DEVIATION 10.18 | 77.02 kiliograms STANDARD_DEVIATION 10.28 | 70.85 kiliograms STANDARD_DEVIATION 14.62 | 74.53 kiliograms STANDARD_DEVIATION 12.37 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 67 | 0 / 70 | 0 / 71 |
| other Total, other adverse events | 38 / 69 | 46 / 67 | 30 / 70 | 34 / 71 |
| serious Total, serious adverse events | 0 / 69 | 0 / 67 | 0 / 70 | 0 / 71 |
Outcome results
Primary
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
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 2 g of Zoliflodacin | 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 | 3 hour post dose | -1.6 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 24 hour post dose | -2.9 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 6 hour post dose | -2.0 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 4 hour post dose | -2.4 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 0.5 hour post dose | -3.2 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 12 hour post dose | -2.8 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 2 hour post dose | -2.3 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 1 hour post dose | -1.9 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 8 hour post dose | -5.6 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 4 hour post dose | 0.1 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 0.5 hour post dose | -1.0 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 1 hour post dose | 0.1 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 2 hour post dose | 0.1 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 3 hour post dose | 0.1 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 6 hour post dose | -0.7 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 8 hour post dose | -4.7 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 12 hour post dose | -0.4 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 24 hour post dose | -0.3 milliseconds (msec) |
| Placebo | 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 | 2 hour post dose | -2.2 milliseconds (msec) |
| Placebo | 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 | 0.5 hour post dose | -2.1 milliseconds (msec) |
| Placebo | 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 | 8 hour post dose | -4.4 milliseconds (msec) |
| Placebo | 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 | 1 hour post dose | -2.3 milliseconds (msec) |
| Placebo | 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 | 24 hour post dose | -2.2 milliseconds (msec) |
| Placebo | 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 | 4 hour post dose | -3.3 milliseconds (msec) |
| Placebo | 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 | 3 hour post dose | -2.6 milliseconds (msec) |
| Placebo | 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 | 12 hour post dose | -2.2 milliseconds (msec) |
| Placebo | 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 | 6 hour post dose | -2.3 milliseconds (msec) |
Comparison: 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.
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Comparison: 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).
Secondary
Apparent Oral Clearance (CL/F) of Zoliflodacin
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 g of Zoliflodacin | Apparent Oral Clearance (CL/F) of Zoliflodacin | 20.08 Liter/hour | Standard Deviation 5.74 |
| 4 g of Zoliflodacin | Apparent Oral Clearance (CL/F) of Zoliflodacin | 23.77 Liter/hour | Standard Deviation 6.34 |
Secondary
Apparent Volume of Distribution (Vz/F) of Zoliflodacin
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 g of Zoliflodacin | Apparent Volume of Distribution (Vz/F) of Zoliflodacin | 160.55 Liter | Standard Deviation 50.46 |
| 4 g of Zoliflodacin | Apparent Volume of Distribution (Vz/F) of Zoliflodacin | 204.29 Liter | Standard Deviation 55.13 |
Secondary
Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0 - Infinity)) for Zoliflodacin
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 g of Zoliflodacin | Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0 - Infinity)) for Zoliflodacin | 108300 h x ng/mL | Standard Deviation 32980 |
| 4 g of Zoliflodacin | Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0 - Infinity)) for Zoliflodacin | 181400 h x ng/mL | Standard Deviation 52890 |
Secondary
Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 g of Zoliflodacin | Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin | 102700 h*ng/mL | Standard Deviation 28580 |
| 4 g of Zoliflodacin | Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin | 177300 h*ng/mL | Standard Deviation 52370 |
Secondary
Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP)
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).
Population: Any participants who received study product for that dosing period and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AST: 24 hour post dose | -2.9 U/L | Standard Deviation 3 |
| 2 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AST: Follow up | 0.1 U/L | Standard Deviation 5.6 |
| 2 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | ALT: 24 hour post dose | -2.2 U/L | Standard Deviation 4.1 |
| 2 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | ALT: Follow up | -0.7 U/L | Standard Deviation 6.9 |
| 2 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AP: 24 hour post dose | -5.2 U/L | Standard Deviation 6.3 |
| 2 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AP: Follow up | -1.7 U/L | Standard Deviation 8.1 |
| 4 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AP: Follow up | -0.4 U/L | Standard Deviation 7 |
| 4 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | ALT: Follow up | 1.6 U/L | Standard Deviation 7.5 |
| 4 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AST: 24 hour post dose | -2.7 U/L | Standard Deviation 5.6 |
| 4 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | ALT: 24 hour post dose | -1.7 U/L | Standard Deviation 2.7 |
| 4 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AST: Follow up | 0.0 U/L | Standard Deviation 4 |
| 4 g of Zoliflodacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AP: 24 hour post dose | -3.9 U/L | Standard Deviation 4.6 |
| Placebo | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AST: Follow up | -0.5 U/L | Standard Deviation 3.3 |
| Placebo | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | ALT: 24 hour post dose | -1.7 U/L | Standard Deviation 4 |
| Placebo | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | ALT: Follow up | -0.6 U/L | Standard Deviation 4.2 |
| Placebo | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AP: Follow up | -0.7 U/L | Standard Deviation 4.8 |
| Placebo | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AP: 24 hour post dose | -4.1 U/L | Standard Deviation 4.9 |
| Placebo | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AST: 24 hour post dose | -2.7 U/L | Standard Deviation 3.5 |
| 400 mg of Moxifloxacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AP: 24 hour post dose | -4.2 U/L | Standard Deviation 5.8 |
| 400 mg of Moxifloxacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AP: Follow up | 1.0 U/L | Standard Deviation 7 |
| 400 mg of Moxifloxacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AST: Follow up | 0.6 U/L | Standard Deviation 5.9 |
| 400 mg of Moxifloxacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | ALT: Follow up | 0.8 U/L | Standard Deviation 4.3 |
| 400 mg of Moxifloxacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | AST: 24 hour post dose | -2.8 U/L | Standard Deviation 4.4 |
| 400 mg of Moxifloxacin | Changes From Baseline for Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) | ALT: 24 hour post dose | -1.4 U/L | Standard Deviation 3.8 |
Secondary
Changes From Baseline for Blood Pressure - Diastolic
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).
Population: Any participants who received study product and had post dose assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | 24 hour post dose | 0.2 mmHg | Standard Deviation 5.3 |
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | 2 hour post dose | -0.4 mmHg | Standard Deviation 6 |
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | Follow up | 2.2 mmHg | Standard Deviation 5.3 |
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | 4 hour post dose | -0.4 mmHg | Standard Deviation 4.9 |
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | 1 hour post dose | 0.3 mmHg | Standard Deviation 5.3 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | 4 hour post dose | -2.3 mmHg | Standard Deviation 5.3 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | 24 hour post dose | -0.5 mmHg | Standard Deviation 5.7 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | Follow up | 0.5 mmHg | Standard Deviation 5.5 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | 2 hour post dose | -0.9 mmHg | Standard Deviation 5.1 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Diastolic | 1 hour post dose | 0.3 mmHg | Standard Deviation 4.8 |
| Placebo | Changes From Baseline for Blood Pressure - Diastolic | 4 hour post dose | 1.1 mmHg | Standard Deviation 5.7 |
| Placebo | Changes From Baseline for Blood Pressure - Diastolic | 1 hour post dose | 0.8 mmHg | Standard Deviation 6.1 |
| Placebo | Changes From Baseline for Blood Pressure - Diastolic | 2 hour post dose | 0.6 mmHg | Standard Deviation 6.7 |
| Placebo | Changes From Baseline for Blood Pressure - Diastolic | 24 hour post dose | 1.4 mmHg | Standard Deviation 5.4 |
| Placebo | Changes From Baseline for Blood Pressure - Diastolic | Follow up | 2.7 mmHg | Standard Deviation 6.7 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Diastolic | 24 hour post dose | 1.1 mmHg | Standard Deviation 5.5 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Diastolic | 2 hour post dose | 1.2 mmHg | Standard Deviation 5.5 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Diastolic | 1 hour post dose | 1.5 mmHg | Standard Deviation 5.3 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Diastolic | 4 hour post dose | -0.1 mmHg | Standard Deviation 5.5 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Diastolic | Follow up | 3.8 mmHg | Standard Deviation 7.2 |
Secondary
Changes From Baseline for Blood Pressure - Systolic
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).
Population: Any participants who received study product and had post dose assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | 24 hour post dose | 0.0 mmHg | Standard Deviation 8.2 |
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | 2 hour post dose | 0.4 mmHg | Standard Deviation 8 |
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | Follow up | 3.5 mmHg | Standard Deviation 8.2 |
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | 4 hour post dose | 0.1 mmHg | Standard Deviation 7.1 |
| 2 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | 1 hour post dose | 0.8 mmHg | Standard Deviation 7.3 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | 4 hour post dose | -0.9 mmHg | Standard Deviation 7.5 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | 24 hour post dose | -0.4 mmHg | Standard Deviation 7.8 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | Follow up | 2.3 mmHg | Standard Deviation 6.9 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | 2 hour post dose | -0.3 mmHg | Standard Deviation 7.6 |
| 4 g of Zoliflodacin | Changes From Baseline for Blood Pressure - Systolic | 1 hour post dose | 1.3 mmHg | Standard Deviation 7.9 |
| Placebo | Changes From Baseline for Blood Pressure - Systolic | 4 hour post dose | 1.0 mmHg | Standard Deviation 7.6 |
| Placebo | Changes From Baseline for Blood Pressure - Systolic | 1 hour post dose | 0.8 mmHg | Standard Deviation 7.6 |
| Placebo | Changes From Baseline for Blood Pressure - Systolic | 2 hour post dose | 1.0 mmHg | Standard Deviation 8.6 |
| Placebo | Changes From Baseline for Blood Pressure - Systolic | 24 hour post dose | 1.1 mmHg | Standard Deviation 7.3 |
| Placebo | Changes From Baseline for Blood Pressure - Systolic | Follow up | 3.7 mmHg | Standard Deviation 9.2 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Systolic | 24 hour post dose | 0.5 mmHg | Standard Deviation 6.9 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Systolic | 2 hour post dose | -0.5 mmHg | Standard Deviation 6.8 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Systolic | 1 hour post dose | 0.4 mmHg | Standard Deviation 7.8 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Systolic | 4 hour post dose | -1.7 mmHg | Standard Deviation 7.7 |
| 400 mg of Moxifloxacin | Changes From Baseline for Blood Pressure - Systolic | Follow up | 5.0 mmHg | Standard Deviation 8.4 |
Secondary
Changes From Baseline for Erythrocytes
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).
Population: Any participants who received study product and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Erythrocytes | Erythrocytes: 24 hour post dose | 0.050 10^6 cells/microliter | Standard Deviation 0.243 |
| 2 g of Zoliflodacin | Changes From Baseline for Erythrocytes | Erythrocytes: Follow up | -0.005 10^6 cells/microliter | Standard Deviation 0.28 |
| 4 g of Zoliflodacin | Changes From Baseline for Erythrocytes | Erythrocytes: Follow up | -0.088 10^6 cells/microliter | Standard Deviation 0.249 |
| 4 g of Zoliflodacin | Changes From Baseline for Erythrocytes | Erythrocytes: 24 hour post dose | -0.008 10^6 cells/microliter | Standard Deviation 0.228 |
| Placebo | Changes From Baseline for Erythrocytes | Erythrocytes: 24 hour post dose | -0.002 10^6 cells/microliter | Standard Deviation 0.233 |
| Placebo | Changes From Baseline for Erythrocytes | Erythrocytes: Follow up | -0.029 10^6 cells/microliter | Standard Deviation 0.212 |
| 400 mg of Moxifloxacin | Changes From Baseline for Erythrocytes | Erythrocytes: 24 hour post dose | -0.031 10^6 cells/microliter | Standard Deviation 0.253 |
| 400 mg of Moxifloxacin | Changes From Baseline for Erythrocytes | Erythrocytes: Follow up | -0.053 10^6 cells/microliter | Standard Deviation 0.248 |
Secondary
Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated
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).
Population: Any participants who received study product and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated | GFR: Follow up | -5.3 mL/minute | Standard Deviation 16.3 |
| 2 g of Zoliflodacin | Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated | GFR: 24 hour post dose | -10.4 mL/minute | Standard Deviation 11.1 |
| 4 g of Zoliflodacin | Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated | GFR: 24 hour post dose | -9.5 mL/minute | Standard Deviation 8.1 |
| 4 g of Zoliflodacin | Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated | GFR: Follow up | 1.8 mL/minute | Standard Deviation 11 |
| Placebo | Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated | GFR: 24 hour post dose | -0.1 mL/minute | Standard Deviation 8.1 |
| Placebo | Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated | GFR: Follow up | -0.7 mL/minute | Standard Deviation 8.5 |
| 400 mg of Moxifloxacin | Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated | GFR: Follow up | 1.5 mL/minute | Standard Deviation 11.9 |
| 400 mg of Moxifloxacin | Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated | GFR: 24 hour post dose | -6.2 mL/minute | Standard Deviation 10.3 |
Secondary
Changes From Baseline for Hematocrit
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).
Population: Any participants who received study product and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Hematocrit | Hematocrit: 24 hour post dose | 0.39 volume percentage of RBC in blood | Standard Deviation 2.04 |
| 2 g of Zoliflodacin | Changes From Baseline for Hematocrit | Hematocrit: Follow up | -0.03 volume percentage of RBC in blood | Standard Deviation 2.26 |
| 4 g of Zoliflodacin | Changes From Baseline for Hematocrit | Hematocrit: Follow up | -0.69 volume percentage of RBC in blood | Standard Deviation 2.15 |
| 4 g of Zoliflodacin | Changes From Baseline for Hematocrit | Hematocrit: 24 hour post dose | -0.10 volume percentage of RBC in blood | Standard Deviation 2.02 |
| Placebo | Changes From Baseline for Hematocrit | Hematocrit: 24 hour post dose | 0.08 volume percentage of RBC in blood | Standard Deviation 2.08 |
| Placebo | Changes From Baseline for Hematocrit | Hematocrit: Follow up | -0.10 volume percentage of RBC in blood | Standard Deviation 1.9 |
| 400 mg of Moxifloxacin | Changes From Baseline for Hematocrit | Hematocrit: 24 hour post dose | -0.26 volume percentage of RBC in blood | Standard Deviation 2.13 |
| 400 mg of Moxifloxacin | Changes From Baseline for Hematocrit | Hematocrit: Follow up | -0.33 volume percentage of RBC in blood | Standard Deviation 2.19 |
Secondary
Changes From Baseline for Hemoglobin
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).
Population: Any participants who received study product and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Hemoglobin | Hemoglobin: 24 hour post dose | 0.15 g/dL | Standard Deviation 0.71 |
| 2 g of Zoliflodacin | Changes From Baseline for Hemoglobin | Hemoglobin: Follow up | -0.01 g/dL | Standard Deviation 0.72 |
| 4 g of Zoliflodacin | Changes From Baseline for Hemoglobin | Hemoglobin: Follow up | -0.23 g/dL | Standard Deviation 0.68 |
| 4 g of Zoliflodacin | Changes From Baseline for Hemoglobin | Hemoglobin: 24 hour post dose | 0.01 g/dL | Standard Deviation 0.65 |
| Placebo | Changes From Baseline for Hemoglobin | Hemoglobin: 24 hour post dose | 0.04 g/dL | Standard Deviation 0.67 |
| Placebo | Changes From Baseline for Hemoglobin | Hemoglobin: Follow up | -0.06 g/dL | Standard Deviation 0.64 |
| 400 mg of Moxifloxacin | Changes From Baseline for Hemoglobin | Hemoglobin: 24 hour post dose | -0.06 g/dL | Standard Deviation 0.68 |
| 400 mg of Moxifloxacin | Changes From Baseline for Hemoglobin | Hemoglobin: Follow up | -0.13 g/dL | Standard Deviation 0.7 |
Secondary
Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin
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).
Population: Any participants who received study product for that dosing period and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Total Bilirubin: Follow up | 0.01 mg/dL | Standard Deviation 0.21 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Direct Bilirubin: Follow up | -0.01 mg/dL | Standard Deviation 0.06 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Creatinine: Follow up | 0.034 mg/dL | Standard Deviation 0.102 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Magnesium: 24 hour post dose | 0.05 mg/dL | Standard Deviation 0.13 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Total Bilirubin: 24 hour post dose | 0.07 mg/dL | Standard Deviation 0.25 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Glucose (fasting): 24 hour post dose | 4.6 mg/dL | Standard Deviation 7.8 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Glucose (fasting): Follow up | -1.2 mg/dL | Standard Deviation 8.7 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Magnesium: Follow up | 0.04 mg/dL | Standard Deviation 0.12 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Direct Bilirubin: 24 hour post dose | 0.00 mg/dL | Standard Deviation 0.07 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | BUN: 24 hour post dose | 2.1 mg/dL | Standard Deviation 3.2 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | BUN: Follow up | 0.7 mg/dL | Standard Deviation 3.3 |
| 2 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Creatinine: 24 hour post dose | 0.082 mg/dL | Standard Deviation 0.082 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Magnesium: Follow up | 0.00 mg/dL | Standard Deviation 0.13 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Creatinine: 24 hour post dose | 0.086 mg/dL | Standard Deviation 0.072 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Glucose (fasting): Follow up | 1.5 mg/dL | Standard Deviation 9.8 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Total Bilirubin: 24 hour post dose | 0.14 mg/dL | Standard Deviation 0.23 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Total Bilirubin: Follow up | -0.04 mg/dL | Standard Deviation 0.14 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Creatinine: Follow up | -0.011 mg/dL | Standard Deviation 0.089 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Magnesium: 24 hour post dose | 0.03 mg/dL | Standard Deviation 0.13 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | BUN: Follow up | 0.0 mg/dL | Standard Deviation 2.9 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | BUN: 24 hour post dose | 1.6 mg/dL | Standard Deviation 3 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Glucose (fasting): 24 hour post dose | 6.4 mg/dL | Standard Deviation 9.7 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Direct Bilirubin: Follow up | 0.00 mg/dL | Standard Deviation 0.05 |
| 4 g of Zoliflodacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Direct Bilirubin: 24 hour post dose | 0.02 mg/dL | Standard Deviation 0.06 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Creatinine: Follow up | 0.006 mg/dL | Standard Deviation 0.071 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Magnesium: 24 hour post dose | 0.02 mg/dL | Standard Deviation 0.14 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Magnesium: Follow up | 0.02 mg/dL | Standard Deviation 0.13 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Glucose (fasting): 24 hour post dose | 4.2 mg/dL | Standard Deviation 8.3 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Glucose (fasting): Follow up | -0.6 mg/dL | Standard Deviation 8.9 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | BUN: 24 hour post dose | 1.4 mg/dL | Standard Deviation 2.9 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | BUN: Follow up | 0.1 mg/dL | Standard Deviation 3 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Creatinine: 24 hour post dose | 0.003 mg/dL | Standard Deviation 0.059 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Total Bilirubin: 24 hour post dose | -0.01 mg/dL | Standard Deviation 0.24 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Total Bilirubin: Follow up | -0.01 mg/dL | Standard Deviation 0.17 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Direct Bilirubin: 24 hour post dose | 0.00 mg/dL | Standard Deviation 0.06 |
| Placebo | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Direct Bilirubin: Follow up | 0.01 mg/dL | Standard Deviation 0.06 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | BUN: Follow up | -0.2 mg/dL | Standard Deviation 4 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | BUN: 24 hour post dose | 2.5 mg/dL | Standard Deviation 3.4 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Magnesium: 24 hour post dose | 0.01 mg/dL | Standard Deviation 0.14 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Total Bilirubin: Follow up | -0.02 mg/dL | Standard Deviation 0.16 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Glucose (fasting): Follow up | 1.0 mg/dL | Standard Deviation 9.5 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Glucose (fasting): 24 hour post dose | 3.2 mg/dL | Standard Deviation 7.4 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Direct Bilirubin: Follow up | -0.01 mg/dL | Standard Deviation 0.05 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Direct Bilirubin: 24 hour post dose | -0.01 mg/dL | Standard Deviation 0.05 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Creatinine: Follow up | -0.007 mg/dL | Standard Deviation 0.087 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Creatinine: 24 hour post dose | 0.059 mg/dL | Standard Deviation 0.078 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Magnesium: Follow up | 0.01 mg/dL | Standard Deviation 0.12 |
| 400 mg of Moxifloxacin | Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin | Total Bilirubin: 24 hour post dose | -0.04 mg/dL | Standard Deviation 0.2 |
Secondary
Changes From Baseline for Platelets
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).
Population: Any participants who received study product for that dosing period and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Platelets | Platelets: 24 hour post dose | -8.2 10^3 platelets/microliter | Standard Deviation 25.8 |
| 2 g of Zoliflodacin | Changes From Baseline for Platelets | Platelets: Follow up | 1.7 10^3 platelets/microliter | Standard Deviation 27.8 |
| 4 g of Zoliflodacin | Changes From Baseline for Platelets | Platelets: Follow up | 2.9 10^3 platelets/microliter | Standard Deviation 30.4 |
| 4 g of Zoliflodacin | Changes From Baseline for Platelets | Platelets: 24 hour post dose | -10.3 10^3 platelets/microliter | Standard Deviation 26.9 |
| Placebo | Changes From Baseline for Platelets | Platelets: 24 hour post dose | -10.5 10^3 platelets/microliter | Standard Deviation 24.4 |
| Placebo | Changes From Baseline for Platelets | Platelets: Follow up | 6.2 10^3 platelets/microliter | Standard Deviation 30.3 |
| 400 mg of Moxifloxacin | Changes From Baseline for Platelets | Platelets: 24 hour post dose | -15.4 10^3 platelets/microliter | Standard Deviation 23.3 |
| 400 mg of Moxifloxacin | Changes From Baseline for Platelets | Platelets: Follow up | -3.8 10^3 platelets/microliter | Standard Deviation 29.3 |
Secondary
Changes From Baseline for Pulse Rate
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).
Population: Any participants who received study product and had post dose assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Pulse Rate | 24 hour post dose | 4.9 beats/minute | Standard Deviation 7.7 |
| 2 g of Zoliflodacin | Changes From Baseline for Pulse Rate | 2 hour post dose | 3.9 beats/minute | Standard Deviation 7.8 |
| 2 g of Zoliflodacin | Changes From Baseline for Pulse Rate | Follow up | 2.0 beats/minute | Standard Deviation 8.7 |
| 2 g of Zoliflodacin | Changes From Baseline for Pulse Rate | 4 hour post dose | 5.4 beats/minute | Standard Deviation 8.5 |
| 2 g of Zoliflodacin | Changes From Baseline for Pulse Rate | 1 hour post dose | 5.2 beats/minute | Standard Deviation 8.3 |
| 4 g of Zoliflodacin | Changes From Baseline for Pulse Rate | 4 hour post dose | 5.8 beats/minute | Standard Deviation 8.3 |
| 4 g of Zoliflodacin | Changes From Baseline for Pulse Rate | 24 hour post dose | 5.2 beats/minute | Standard Deviation 7.3 |
| 4 g of Zoliflodacin | Changes From Baseline for Pulse Rate | Follow up | 2.8 beats/minute | Standard Deviation 7.7 |
| 4 g of Zoliflodacin | Changes From Baseline for Pulse Rate | 2 hour post dose | 6.5 beats/minute | Standard Deviation 8 |
| 4 g of Zoliflodacin | Changes From Baseline for Pulse Rate | 1 hour post dose | 5.7 beats/minute | Standard Deviation 7.8 |
| Placebo | Changes From Baseline for Pulse Rate | 4 hour post dose | 3.0 beats/minute | Standard Deviation 9.6 |
| Placebo | Changes From Baseline for Pulse Rate | 1 hour post dose | 2.8 beats/minute | Standard Deviation 8.1 |
| Placebo | Changes From Baseline for Pulse Rate | 2 hour post dose | 3.8 beats/minute | Standard Deviation 7.5 |
| Placebo | Changes From Baseline for Pulse Rate | 24 hour post dose | 5.4 beats/minute | Standard Deviation 8.4 |
| Placebo | Changes From Baseline for Pulse Rate | Follow up | 2.0 beats/minute | Standard Deviation 10.3 |
| 400 mg of Moxifloxacin | Changes From Baseline for Pulse Rate | 24 hour post dose | 6.3 beats/minute | Standard Deviation 8.1 |
| 400 mg of Moxifloxacin | Changes From Baseline for Pulse Rate | 2 hour post dose | 5.5 beats/minute | Standard Deviation 5.8 |
| 400 mg of Moxifloxacin | Changes From Baseline for Pulse Rate | 1 hour post dose | 6.9 beats/minute | Standard Deviation 6.8 |
| 400 mg of Moxifloxacin | Changes From Baseline for Pulse Rate | 4 hour post dose | 5.2 beats/minute | Standard Deviation 8.2 |
| 400 mg of Moxifloxacin | Changes From Baseline for Pulse Rate | Follow up | 4.2 beats/minute | Standard Deviation 7.2 |
Secondary
Changes From Baseline for Respiratory Rate
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).
Population: Any participants who received study product and had post dose assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | 24 hour post dose | 0.9 breaths/minute | Standard Deviation 3.1 |
| 2 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | 2 hour post dose | 0.4 breaths/minute | Standard Deviation 3.2 |
| 2 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | Follow up | 0.6 breaths/minute | Standard Deviation 3.1 |
| 2 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | 4 hour post dose | 0.8 breaths/minute | Standard Deviation 3.6 |
| 2 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | 1 hour post dose | 0.8 breaths/minute | Standard Deviation 3.1 |
| 4 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | 4 hour post dose | 1.3 breaths/minute | Standard Deviation 3.3 |
| 4 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | 24 hour post dose | 1.0 breaths/minute | Standard Deviation 2.9 |
| 4 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | Follow up | 1.3 breaths/minute | Standard Deviation 3.3 |
| 4 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | 2 hour post dose | 0.7 breaths/minute | Standard Deviation 2.9 |
| 4 g of Zoliflodacin | Changes From Baseline for Respiratory Rate | 1 hour post dose | 1.1 breaths/minute | Standard Deviation 2.9 |
| Placebo | Changes From Baseline for Respiratory Rate | 4 hour post dose | -0.2 breaths/minute | Standard Deviation 2.7 |
| Placebo | Changes From Baseline for Respiratory Rate | 1 hour post dose | 1.0 breaths/minute | Standard Deviation 2.8 |
| Placebo | Changes From Baseline for Respiratory Rate | 2 hour post dose | -0.3 breaths/minute | Standard Deviation 3 |
| Placebo | Changes From Baseline for Respiratory Rate | 24 hour post dose | 0.6 breaths/minute | Standard Deviation 2.7 |
| Placebo | Changes From Baseline for Respiratory Rate | Follow up | 0.2 breaths/minute | Standard Deviation 3 |
| 400 mg of Moxifloxacin | Changes From Baseline for Respiratory Rate | 24 hour post dose | 0.5 breaths/minute | Standard Deviation 3 |
| 400 mg of Moxifloxacin | Changes From Baseline for Respiratory Rate | 2 hour post dose | 0.0 breaths/minute | Standard Deviation 3 |
| 400 mg of Moxifloxacin | Changes From Baseline for Respiratory Rate | 1 hour post dose | 0.4 breaths/minute | Standard Deviation 3 |
| 400 mg of Moxifloxacin | Changes From Baseline for Respiratory Rate | 4 hour post dose | 0.1 breaths/minute | Standard Deviation 3.1 |
| 400 mg of Moxifloxacin | Changes From Baseline for Respiratory Rate | Follow up | 0.6 breaths/minute | Standard Deviation 3.6 |
Secondary
Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate
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).
Population: Any participants who received study product for that dosing period and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Sodium: 24 hour post dose | 0.2 mmol/L | Standard Deviation 1.9 |
| 2 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Sodium: Follow up | 0.1 mmol/L | Standard Deviation 2.3 |
| 2 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Potassium: 24 hour post dose | 0.26 mmol/L | Standard Deviation 0.41 |
| 2 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Potassium: Follow up | 0.01 mmol/L | Standard Deviation 0.33 |
| 2 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Chloride: 24 hour post dose | 1.3 mmol/L | Standard Deviation 2 |
| 2 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Chloride: Follow up | 0.3 mmol/L | Standard Deviation 2.1 |
| 2 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Bicarbonate: 24 hour post dose | 0.2 mmol/L | Standard Deviation 2.4 |
| 2 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Bicarbonate: Follow up | -0.2 mmol/L | Standard Deviation 2.2 |
| 4 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Chloride: Follow up | -0.3 mmol/L | Standard Deviation 2.3 |
| 4 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Chloride: 24 hour post dose | 1.0 mmol/L | Standard Deviation 1.9 |
| 4 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Sodium: Follow up | -0.3 mmol/L | Standard Deviation 1.7 |
| 4 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Bicarbonate: Follow up | -0.3 mmol/L | Standard Deviation 2.2 |
| 4 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Bicarbonate: 24 hour post dose | 0.1 mmol/L | Standard Deviation 1.8 |
| 4 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Potassium: Follow up | -0.02 mmol/L | Standard Deviation 0.45 |
| 4 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Potassium: 24 hour post dose | 0.25 mmol/L | Standard Deviation 0.39 |
| 4 g of Zoliflodacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Sodium: 24 hour post dose | -0.1 mmol/L | Standard Deviation 1.9 |
| Placebo | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Bicarbonate: 24 hour post dose | 0.6 mmol/L | Standard Deviation 1.9 |
| Placebo | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Potassium: 24 hour post dose | 0.17 mmol/L | Standard Deviation 0.41 |
| Placebo | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Potassium: Follow up | 0.01 mmol/L | Standard Deviation 0.4 |
| Placebo | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Chloride: 24 hour post dose | 1.4 mmol/L | Standard Deviation 2 |
| Placebo | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Chloride: Follow up | 0.5 mmol/L | Standard Deviation 1.7 |
| Placebo | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Bicarbonate: Follow up | 0.3 mmol/L | Standard Deviation 2.1 |
| Placebo | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Sodium: 24 hour post dose | 0.6 mmol/L | Standard Deviation 1.9 |
| Placebo | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Sodium: Follow up | 0.6 mmol/L | Standard Deviation 1.8 |
| 400 mg of Moxifloxacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Potassium: 24 hour post dose | 0.11 mmol/L | Standard Deviation 0.36 |
| 400 mg of Moxifloxacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Potassium: Follow up | -0.01 mmol/L | Standard Deviation 0.41 |
| 400 mg of Moxifloxacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Sodium: Follow up | 0.2 mmol/L | Standard Deviation 1.9 |
| 400 mg of Moxifloxacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Sodium: 24 hour post dose | 0.7 mmol/L | Standard Deviation 1.9 |
| 400 mg of Moxifloxacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Chloride: 24 hour post dose | 1.4 mmol/L | Standard Deviation 2 |
| 400 mg of Moxifloxacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Bicarbonate: Follow up | -0.1 mmol/L | Standard Deviation 2.2 |
| 400 mg of Moxifloxacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Bicarbonate: 24 hour post dose | 0.4 mmol/L | Standard Deviation 2.1 |
| 400 mg of Moxifloxacin | Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate | Chloride: Follow up | 0.1 mmol/L | Standard Deviation 2.1 |
Secondary
Changes From Baseline for Temperature
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).
Population: Any participants who received study product and had post dose assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Temperature | Follow up | 0.05 Celsius | Standard Deviation 0.28 |
| 2 g of Zoliflodacin | Changes From Baseline for Temperature | 1 hour post dose | 0.08 Celsius | Standard Deviation 0.26 |
| 2 g of Zoliflodacin | Changes From Baseline for Temperature | 2 hour post dose | 0.10 Celsius | Standard Deviation 0.21 |
| 2 g of Zoliflodacin | Changes From Baseline for Temperature | 4 hour post dose | 0.08 Celsius | Standard Deviation 0.23 |
| 2 g of Zoliflodacin | Changes From Baseline for Temperature | 24 hour post dose | 0.09 Celsius | Standard Deviation 0.27 |
| 4 g of Zoliflodacin | Changes From Baseline for Temperature | 2 hour post dose | 0.06 Celsius | Standard Deviation 0.22 |
| 4 g of Zoliflodacin | Changes From Baseline for Temperature | 4 hour post dose | 0.05 Celsius | Standard Deviation 0.27 |
| 4 g of Zoliflodacin | Changes From Baseline for Temperature | 1 hour post dose | 0.03 Celsius | Standard Deviation 0.25 |
| 4 g of Zoliflodacin | Changes From Baseline for Temperature | 24 hour post dose | 0.06 Celsius | Standard Deviation 0.27 |
| 4 g of Zoliflodacin | Changes From Baseline for Temperature | Follow up | -0.02 Celsius | Standard Deviation 0.31 |
| Placebo | Changes From Baseline for Temperature | 1 hour post dose | 0.03 Celsius | Standard Deviation 0.27 |
| Placebo | Changes From Baseline for Temperature | 2 hour post dose | 0.09 Celsius | Standard Deviation 0.24 |
| Placebo | Changes From Baseline for Temperature | Follow up | 0.00 Celsius | Standard Deviation 0.28 |
| Placebo | Changes From Baseline for Temperature | 4 hour post dose | 0.09 Celsius | Standard Deviation 0.24 |
| Placebo | Changes From Baseline for Temperature | 24 hour post dose | 0.04 Celsius | Standard Deviation 0.27 |
| 400 mg of Moxifloxacin | Changes From Baseline for Temperature | 4 hour post dose | 0.13 Celsius | Standard Deviation 0.26 |
| 400 mg of Moxifloxacin | Changes From Baseline for Temperature | 2 hour post dose | 0.11 Celsius | Standard Deviation 0.23 |
| 400 mg of Moxifloxacin | Changes From Baseline for Temperature | 1 hour post dose | 0.05 Celsius | Standard Deviation 0.31 |
| 400 mg of Moxifloxacin | Changes From Baseline for Temperature | 24 hour post dose | 0.10 Celsius | Standard Deviation 0.26 |
| 400 mg of Moxifloxacin | Changes From Baseline for Temperature | Follow up | 0.05 Celsius | Standard Deviation 0.29 |
Secondary
Changes From Baseline for Total Protein and Albumin
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).
Population: Any participants who received study product for that dosing period and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for Total Protein and Albumin | Total Protein: 24 hour post dose | -0.42 g/dL | Standard Deviation 0.45 |
| 2 g of Zoliflodacin | Changes From Baseline for Total Protein and Albumin | Total Protein: Follow up | -0.01 g/dL | Standard Deviation 0.49 |
| 2 g of Zoliflodacin | Changes From Baseline for Total Protein and Albumin | Albumin: 24 hour post dose | -0.28 g/dL | Standard Deviation 0.25 |
| 2 g of Zoliflodacin | Changes From Baseline for Total Protein and Albumin | Albumin: Follow up | 0.00 g/dL | Standard Deviation 0.28 |
| 4 g of Zoliflodacin | Changes From Baseline for Total Protein and Albumin | Total Protein: Follow up | -0.06 g/dL | Standard Deviation 0.39 |
| 4 g of Zoliflodacin | Changes From Baseline for Total Protein and Albumin | Albumin: 24 hour post dose | -0.30 g/dL | Standard Deviation 0.23 |
| 4 g of Zoliflodacin | Changes From Baseline for Total Protein and Albumin | Albumin: Follow up | -0.05 g/dL | Standard Deviation 0.22 |
| 4 g of Zoliflodacin | Changes From Baseline for Total Protein and Albumin | Total Protein: 24 hour post dose | -0.42 g/dL | Standard Deviation 0.39 |
| Placebo | Changes From Baseline for Total Protein and Albumin | Albumin: 24 hour post dose | -0.30 g/dL | Standard Deviation 0.24 |
| Placebo | Changes From Baseline for Total Protein and Albumin | Total Protein: Follow up | -0.01 g/dL | Standard Deviation 0.4 |
| Placebo | Changes From Baseline for Total Protein and Albumin | Albumin: Follow up | 0.01 g/dL | Standard Deviation 0.23 |
| Placebo | Changes From Baseline for Total Protein and Albumin | Total Protein: 24 hour post dose | -0.45 g/dL | Standard Deviation 0.43 |
| 400 mg of Moxifloxacin | Changes From Baseline for Total Protein and Albumin | Albumin: Follow up | 0.02 g/dL | Standard Deviation 0.23 |
| 400 mg of Moxifloxacin | Changes From Baseline for Total Protein and Albumin | Total Protein: Follow up | 0.03 g/dL | Standard Deviation 0.41 |
| 400 mg of Moxifloxacin | Changes From Baseline for Total Protein and Albumin | Total Protein: 24 hour post dose | -0.45 g/dL | Standard Deviation 0.38 |
| 400 mg of Moxifloxacin | Changes From Baseline for Total Protein and Albumin | Albumin: 24 hour post dose | -0.32 g/dL | Standard Deviation 0.23 |
Secondary
Changes From Baseline for White Blood Cells With Differentials
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).
Population: Any participants who received study product and had post dose laboratory assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Leukocytes: 24 hour post dose | -246.4 cells/microliter | Standard Deviation 1031.5 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Monocytes: Follow up | 4.6 cells/microliter | Standard Deviation 118.8 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Neutrophils: Follow up | -272.2 cells/microliter | Standard Deviation 945.4 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Monocytes: 24 hour post dose | -7.8 cells/microliter | Standard Deviation 118.2 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Basophils: Follow up | 0.6 cells/microliter | Standard Deviation 15.7 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Basophils: 24 hour post dose | -3.4 cells/microliter | Standard Deviation 13.8 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Lymphocytes: 24 hour post dose | 3.4 cells/microliter | Standard Deviation 583.2 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Eosinophils: 24 hour post dose | 9.4 cells/microliter | Standard Deviation 65.1 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Leukocytes: Follow up | -273.5 cells/microliter | Standard Deviation 1253.1 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Neutrophils: 24 hour post dose | -248.0 cells/microliter | Standard Deviation 667.7 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Lymphocytes: Follow up | -19.6 cells/microliter | Standard Deviation 497.9 |
| 2 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Eosinophils: Follow up | 12.9 cells/microliter | Standard Deviation 80.9 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Lymphocytes: Follow up | -74.1 cells/microliter | Standard Deviation 530.5 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Monocytes: 24 hour post dose | -13.9 cells/microliter | Standard Deviation 125.3 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Leukocytes: 24 hour post dose | -129.9 cells/microliter | Standard Deviation 1249.6 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Eosinophils: 24 hour post dose | 4.0 cells/microliter | Standard Deviation 71 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Monocytes: Follow up | -7.6 cells/microliter | Standard Deviation 158.7 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Neutrophils: 24 hour post dose | -39.6 cells/microliter | Standard Deviation 955.3 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Basophils: 24 hour post dose | -2.5 cells/microliter | Standard Deviation 13.3 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Neutrophils: Follow up | 220.4 cells/microliter | Standard Deviation 1136.7 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Basophils: Follow up | -0.5 cells/microliter | Standard Deviation 14.9 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Lymphocytes: 24 hour post dose | -77.9 cells/microliter | Standard Deviation 499.6 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Eosinophils: Follow up | 2.2 cells/microliter | Standard Deviation 83.9 |
| 4 g of Zoliflodacin | Changes From Baseline for White Blood Cells With Differentials | Leukocytes: Follow up | 140.3 cells/microliter | Standard Deviation 1486.1 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Eosinophils: 24 hour post dose | 6.0 cells/microliter | Standard Deviation 72.8 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Eosinophils: Follow up | 0.7 cells/microliter | Standard Deviation 69.7 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Leukocytes: 24 hour post dose | -64.3 cells/microliter | Standard Deviation 1130.2 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Leukocytes: Follow up | 35.8 cells/microliter | Standard Deviation 1153.9 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Neutrophils: 24 hour post dose | -54.3 cells/microliter | Standard Deviation 1036.5 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Neutrophils: Follow up | -36.1 cells/microliter | Standard Deviation 986.4 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Lymphocytes: 24 hour post dose | -1.9 cells/microliter | Standard Deviation 549.7 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Lymphocytes: Follow up | 96.9 cells/microliter | Standard Deviation 482.9 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Monocytes: 24 hour post dose | -10.6 cells/microliter | Standard Deviation 123.7 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Monocytes: Follow up | -25.4 cells/microliter | Standard Deviation 141 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Basophils: 24 hour post dose | -3.3 cells/microliter | Standard Deviation 13.5 |
| Placebo | Changes From Baseline for White Blood Cells With Differentials | Basophils: Follow up | -0.2 cells/microliter | Standard Deviation 10.7 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Eosinophils: 24 hour post dose | 8.2 cells/microliter | Standard Deviation 64.7 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Lymphocytes: Follow up | -33.7 cells/microliter | Standard Deviation 625.8 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Lymphocytes: 24 hour post dose | 79.4 cells/microliter | Standard Deviation 556.9 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Eosinophils: Follow up | 2.3 cells/microliter | Standard Deviation 61.2 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Neutrophils: Follow up | -59.2 cells/microliter | Standard Deviation 1216.6 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Neutrophils: 24 hour post dose | -351.3 cells/microliter | Standard Deviation 1008.5 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Basophils: Follow up | 1.4 cells/microliter | Standard Deviation 14.7 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Basophils: 24 hour post dose | -3.1 cells/microliter | Standard Deviation 14.4 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Leukocytes: Follow up | -84.1 cells/microliter | Standard Deviation 1477.6 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Leukocytes: 24 hour post dose | -282.9 cells/microliter | Standard Deviation 1075.4 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Monocytes: 24 hour post dose | -16.1 cells/microliter | Standard Deviation 114.8 |
| 400 mg of Moxifloxacin | Changes From Baseline for White Blood Cells With Differentials | Monocytes: Follow up | 5.2 cells/microliter | Standard Deviation 138.9 |
Secondary
Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval
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
Population: Any participants who received study product and had post dose ECG assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 4 hr post dose | -5.0 milliseconds (msec) | Standard Deviation 13.8 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 4 hr post dose | -2.0 milliseconds (msec) | Standard Deviation 3.9 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 1 hr post dose | -3.6 milliseconds (msec) | Standard Deviation 13.1 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 2 hr post dose | 1.2 milliseconds (msec) | Standard Deviation 8.3 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 2 hr post dose | -38.5 milliseconds (msec) | Standard Deviation 99.7 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 2 hr post dose | -5.3 milliseconds (msec) | Standard Deviation 14.6 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 4 hr post dose | -38.8 milliseconds (msec) | Standard Deviation 94.7 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: Follow up | -1.2 milliseconds (msec) | Standard Deviation 8.8 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 24 hr post dose | -6.8 milliseconds (msec) | Standard Deviation 12.3 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 24 hr post dose | 1.5 milliseconds (msec) | Standard Deviation 8.5 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 1 hr post dose | -1.8 milliseconds (msec) | Standard Deviation 4.1 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: Follow up | -7.1 milliseconds (msec) | Standard Deviation 20.7 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 1 hr post dose | 1.5 milliseconds (msec) | Standard Deviation 10.8 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 1 hr post dose | 1.2 milliseconds (msec) | Standard Deviation 8.9 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 4 hr post dose | -0.3 milliseconds (msec) | Standard Deviation 8 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 2 hr post dose | 0.4 milliseconds (msec) | Standard Deviation 9.9 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: Follow up | -39.6 milliseconds (msec) | Standard Deviation 112.7 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 4 hr post dose | 0.7 milliseconds (msec) | Standard Deviation 10.8 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 1 hr post dose | -34.9 milliseconds (msec) | Standard Deviation 99.9 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 24 hr post dose | -57.6 milliseconds (msec) | Standard Deviation 83.5 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 24 hr post dose | -2.7 milliseconds (msec) | Standard Deviation 4.9 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: Follow up | -1.4 milliseconds (msec) | Standard Deviation 12.7 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: Follow up | -1.4 milliseconds (msec) | Standard Deviation 6 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 24 hr post dose | 1.1 milliseconds (msec) | Standard Deviation 7.8 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 2 hr post dose | -1.9 milliseconds (msec) | Standard Deviation 6.6 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: Follow up | -0.2 milliseconds (msec) | Standard Deviation 12.8 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 4 hr post dose | -54.3 milliseconds (msec) | Standard Deviation 102.3 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 4 hr post dose | -1.0 milliseconds (msec) | Standard Deviation 5.2 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 2 hr post dose | -68.7 milliseconds (msec) | Standard Deviation 82 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 24 hr post dose | -66.9 milliseconds (msec) | Standard Deviation 91.3 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 1 hr post dose | -6.2 milliseconds (msec) | Standard Deviation 12.2 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 1 hr post dose | 0.6 milliseconds (msec) | Standard Deviation 9.3 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 24 hr post dose | 0.7 milliseconds (msec) | Standard Deviation 7.9 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: Follow up | -45.6 milliseconds (msec) | Standard Deviation 108.6 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 2 hr post dose | -7.6 milliseconds (msec) | Standard Deviation 15.6 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 24 hr post dose | 1.9 milliseconds (msec) | Standard Deviation 9.3 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 1 hr post dose | -48.4 milliseconds (msec) | Standard Deviation 86 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: Follow up | 0.3 milliseconds (msec) | Standard Deviation 6.9 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 4 hr post dose | -9.1 milliseconds (msec) | Standard Deviation 18.3 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 2 hr post dose | 2.0 milliseconds (msec) | Standard Deviation 10.2 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 24 hr post dose | -7.6 milliseconds (msec) | Standard Deviation 15.9 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 4 hr post dose | -1.4 milliseconds (msec) | Standard Deviation 8.3 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: Follow up | -1.9 milliseconds (msec) | Standard Deviation 9.8 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 2 hr post dose | -0.7 milliseconds (msec) | Standard Deviation 7.8 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 24 hr post dose | -1.1 milliseconds (msec) | Standard Deviation 6.8 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 2 hr post dose | -1.4 milliseconds (msec) | Standard Deviation 4.9 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 1 hr post dose | -0.6 milliseconds (msec) | Standard Deviation 5.1 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 1 hr post dose | 0.0 milliseconds (msec) | Standard Deviation 7.7 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 4 hr post dose | -1.3 milliseconds (msec) | Standard Deviation 12.2 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: Follow up | -6.6 milliseconds (msec) | Standard Deviation 21.1 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: Follow up | -32.4 milliseconds (msec) | Standard Deviation 125.5 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 1 hr post dose | 1.3 milliseconds (msec) | Standard Deviation 8.5 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 2 hr post dose | 0.6 milliseconds (msec) | Standard Deviation 7.6 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 4 hr post dose | -0.4 milliseconds (msec) | Standard Deviation 7.8 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 24 hr post dose | 0.5 milliseconds (msec) | Standard Deviation 8.2 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: Follow up | -3.1 milliseconds (msec) | Standard Deviation 9.9 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 4 hr post dose | -0.7 milliseconds (msec) | Standard Deviation 5.1 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: Follow up | -8.3 milliseconds (msec) | Standard Deviation 20.2 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 1 hr post dose | -0.4 milliseconds (msec) | Standard Deviation 9.2 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 2 hr post dose | -2.9 milliseconds (msec) | Standard Deviation 9.5 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 1 hr post dose | 0.4 milliseconds (msec) | Standard Deviation 5.1 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 24 hr post dose | -0.9 milliseconds (msec) | Standard Deviation 5 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: Follow up | -1.1 milliseconds (msec) | Standard Deviation 5.3 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 2 hr post dose | -0.7 milliseconds (msec) | Standard Deviation 5.9 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 1 hr post dose | -2.5 milliseconds (msec) | Standard Deviation 11.1 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 2 hr post dose | -3.6 milliseconds (msec) | Standard Deviation 13.3 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 4 hr post dose | -3.8 milliseconds (msec) | Standard Deviation 14.3 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 24 hr post dose | -9.9 milliseconds (msec) | Standard Deviation 15.1 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 1 hr post dose | -14.1 milliseconds (msec) | Standard Deviation 80.6 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 2 hr post dose | -3.3 milliseconds (msec) | Standard Deviation 94 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 4 hr post dose | -4.8 milliseconds (msec) | Standard Deviation 113.1 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 24 hr post dose | -45.9 milliseconds (msec) | Standard Deviation 106.1 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 4 hr post dose | -3.0 milliseconds (msec) | Standard Deviation 9.9 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 24 hr post dose | -3.5 milliseconds (msec) | Standard Deviation 10.3 |
| Placebo | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: Follow up | -3.8 milliseconds (msec) | Standard Deviation 14.4 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 24 hr post dose | 4.1 milliseconds (msec) | Standard Deviation 11.6 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 2 hr post dose | -59.0 milliseconds (msec) | Standard Deviation 107.3 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 2 hr post dose | -1.5 milliseconds (msec) | Standard Deviation 8 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 24 hr post dose | -1.1 milliseconds (msec) | Standard Deviation 7 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 4 hr post dose | -0.9 milliseconds (msec) | Standard Deviation 11.6 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 4 hr post dose | -46.6 milliseconds (msec) | Standard Deviation 114 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 4 hr post dose | -1.6 milliseconds (msec) | Standard Deviation 7.4 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: 1 hr post dose | -0.5 milliseconds (msec) | Standard Deviation 6.7 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 2 hr post dose | 0.4 milliseconds (msec) | Standard Deviation 11.5 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 24 hr post dose | -56.8 milliseconds (msec) | Standard Deviation 87 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 2 hr post dose | 10.6 milliseconds (msec) | Standard Deviation 11.5 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 1 hr post dose | 9.2 milliseconds (msec) | Standard Deviation 10.9 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: Follow up | -10.0 milliseconds (msec) | Standard Deviation 18.4 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: Follow up | -62.1 milliseconds (msec) | Standard Deviation 103.1 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 1 hr post dose | 1.3 milliseconds (msec) | Standard Deviation 11.7 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: 4 hr post dose | 8.5 milliseconds (msec) | Standard Deviation 12 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: Follow up | -0.9 milliseconds (msec) | Standard Deviation 13.3 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 4 hr post dose | 2.0 milliseconds (msec) | Standard Deviation 16.1 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval: 24 hr post dose | 2.8 milliseconds (msec) | Standard Deviation 11.3 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 24 hr post dose | -3.7 milliseconds (msec) | Standard Deviation 14.1 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 2 hr post dose | 2.3 milliseconds (msec) | Standard Deviation 16.7 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QTcF Interval: Follow up | -1.4 milliseconds (msec) | Standard Deviation 14.9 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | RR Interval: 1 hr post dose | -74.5 milliseconds (msec) | Standard Deviation 100.2 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QT Interval: 1 hr post dose | -1.4 milliseconds (msec) | Standard Deviation 12.6 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | QRS Duration: Follow up | -0.2 milliseconds (msec) | Standard Deviation 8.6 |
Secondary
Changes From Baseline in ECG Measures: Ventricular Rate
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
Population: Any participants who received study product and had post dose ECG assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 2 hr post dose | 2.9 beats/minute | Standard Deviation 6.8 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 1 hr post dose | 2.4 beats/minute | Standard Deviation 6.6 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 4 hr post dose | 2.8 beats/minute | Standard Deviation 6.6 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: Follow up | 2.8 beats/minute | Standard Deviation 8.2 |
| 2 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 24 hr post dose | 3.9 beats/minute | Standard Deviation 5.8 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 4 hr post dose | 4.1 beats/minute | Standard Deviation 7.5 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 1 hr post dose | 3.3 beats/minute | Standard Deviation 5.3 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 2 hr post dose | 4.6 beats/minute | Standard Deviation 6.2 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 24 hr post dose | 4.6 beats/minute | Standard Deviation 6.4 |
| 4 g of Zoliflodacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: Follow up | 3.1 beats/minute | Standard Deviation 7.3 |
| Placebo | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 4 hr post dose | 0.2 beats/minute | Standard Deviation 7.3 |
| Placebo | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 1 hr post dose | 0.9 beats/minute | Standard Deviation 5.1 |
| Placebo | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: Follow up | 1.8 beats/minute | Standard Deviation 8.9 |
| Placebo | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 24 hr post dose | 2.9 beats/minute | Standard Deviation 8 |
| Placebo | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 2 hr post dose | 0.4 beats/minute | Standard Deviation 6.5 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 24 hr post dose | 3.5 beats/minute | Standard Deviation 5.8 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 4 hr post dose | 2.8 beats/minute | Standard Deviation 7.4 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 1 hr post dose | 4.7 beats/minute | Standard Deviation 6.2 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: Follow up | 3.9 beats/minute | Standard Deviation 7 |
| 400 mg of Moxifloxacin | Changes From Baseline in ECG Measures: Ventricular Rate | Ventricular Rate: 2 hr post dose | 3.6 beats/minute | Standard Deviation 6.8 |
Secondary
Elimination Rate Constant (Ke) of Zoliflodacin
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 g of Zoliflodacin | Elimination Rate Constant (Ke) of Zoliflodacin | 0.1267 1/hour | Standard Deviation 0.0159 |
| 4 g of Zoliflodacin | Elimination Rate Constant (Ke) of Zoliflodacin | 0.1174 1/hour | Standard Deviation 0.01467 |
Secondary
Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin
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
Population: Any participants who received study product and had post dose assessments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post dose: T wave: Abnormal, Flat | 6 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post: T wave:Abnormal, Inverted, Asymmetric | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post dose: T wave: Abnormal, Flat | 1 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post: T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post: T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post dose: T wave: Abnormal, Flat | 3 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 2 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post:T wave: Abnormal, Inverted, Asymmetric | 2 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post: T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post: T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post dose: T wave: Abnormal, Flat | 4 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post dose: T wave: Abnormal, Flat | 1 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post dose: T wave: Abnormal, Flat | 4 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post:T wave: Abnormal, Inverted, Asymmetric | 1 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post: T wave:Abnormal, Inverted, Asymmetric | 0 Participants |
| 4 g of Zoliflodacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post dose: T wave: Abnormal, Flat | 4 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post:T wave: Abnormal, Inverted, Asymmetric | 1 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post: T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post dose: T wave: Abnormal, Biphasic | 1 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post dose: T wave: Abnormal, Flat | 2 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post dose: T wave: Abnormal, Flat | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post dose: T wave: Abnormal, Flat | 2 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post dose: T wave: Abnormal, Flat | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post:T wave: Abnormal, Inverted, Asymmetric | 1 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post: T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post dose: T wave: Abnormal, Biphasic | 1 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post dose: T wave: Abnormal, Flat | 2 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post dose: T wave: Abnormal, Flat | 2 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post: T wave:Abnormal, Inverted, Asymmetric | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post:T wave: Abnormal, Inverted, Asymmetric | 1 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post dose: T wave: Abnormal, Flat | 2 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post dose: T wave: Abnormal, Biphasic | 1 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post:T wave: Abnormal, Inverted, Asymmetric | 1 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post dose: T wave: Abnormal, Flat | 0 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post:T wave: Abnormal, Inverted, Asymmetric | 1 Participants |
| Placebo | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post dose: T wave: Abnormal, Biphasic | 1 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post dose: T wave: Abnormal, Flat | 5 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 6 h post:T wave: Abnormal, Inverted, Asymmetric | 1 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post dose: T wave: Abnormal, Flat | 1 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post: T wave:Abnormal, Inverted, Asymmetric | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post dose: T wave: Abnormal, Flat | 1 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post: T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 4 h post dose: T wave: Abnormal, Biphasic | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 12 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 8 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post dose: T wave: Abnormal, Flat | 1 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 3 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 0.5 h post dose: T wave: Abnormal, Flat | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post: T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 24 h post:T wave: Abnormal, Inverted, Asymmetric | 0 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 2 h post dose: T wave: Abnormal, Flat | 1 Participants |
| 400 mg of Moxifloxacin | Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin | 1 h post dose: T wave: Abnormal, Flat | 0 Participants |
Secondary
Maximum Observed Concentration (Cmax) of Zoliflodacin
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 g of Zoliflodacin | Maximum Observed Concentration (Cmax) of Zoliflodacin | 12120 ng/mL | Standard Deviation 2985 |
| 4 g of Zoliflodacin | Maximum Observed Concentration (Cmax) of Zoliflodacin | 20350 ng/mL | Standard Deviation 8682 |
Secondary
Number of Participants With Treatment-emergent Adverse Events Following Administration of Study Product
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).
Population: Any participants who received study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2 g of Zoliflodacin | Number of Participants With Treatment-emergent Adverse Events Following Administration of Study Product | 38 Participants |
| 4 g of Zoliflodacin | Number of Participants With Treatment-emergent Adverse Events Following Administration of Study Product | 46 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events Following Administration of Study Product | 35 Participants |
| 400 mg of Moxifloxacin | Number of Participants With Treatment-emergent Adverse Events Following Administration of Study Product | 41 Participants |
Secondary
Number of Participants With Treatment-emergent Serious Adverse Events Following Administration of Zoliflodacin and Moxifloxacin
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).
Population: Any participants who received study product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2 g of Zoliflodacin | Number of Participants With Treatment-emergent Serious Adverse Events Following Administration of Zoliflodacin and Moxifloxacin | 0 Participants |
| 4 g of Zoliflodacin | Number of Participants With Treatment-emergent Serious Adverse Events Following Administration of Zoliflodacin and Moxifloxacin | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Serious Adverse Events Following Administration of Zoliflodacin and Moxifloxacin | 0 Participants |
| 400 mg of Moxifloxacin | Number of Participants With Treatment-emergent Serious Adverse Events Following Administration of Zoliflodacin and Moxifloxacin | 0 Participants |
Secondary
Occurrence of Urinalysis Adverse Events Following Administration of Study Product
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).
Population: Any participants who received study product and had post dose laboratory assessments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Erythrocytes microscopic: 24 hour post dose | 2 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Occult blood dipstick: Follow up | 4 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Protein dipstick: Follow up | 2 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Bacteria microscopic: 24 hour post dose | 0 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Occult blood dipstick: 24 hour post dose | 1 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Leukocytes microscopic: Follow up | 0 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Glucose dipstick: Follow up | 0 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Glucose dipstick: 24 hour post dose | 0 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Leukocytes microscopic: 24 hour post dose | 0 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Erythrocytes microscopic: Follow up | 3 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Protein dipstick: 24 hour post dose | 1 Participants |
| 2 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Bacteria microscopic: Follow up | 2 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Occult blood dipstick: 24 hour post dose | 4 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Glucose dipstick: 24 hour post dose | 0 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Glucose dipstick: Follow up | 0 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Protein dipstick: 24 hour post dose | 1 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Protein dipstick: Follow up | 0 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Occult blood dipstick: Follow up | 2 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Erythrocytes microscopic: 24 hour post dose | 2 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Erythrocytes microscopic: Follow up | 1 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Leukocytes microscopic: 24 hour post dose | 1 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Leukocytes microscopic: Follow up | 0 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Bacteria microscopic: 24 hour post dose | 3 Participants |
| 4 g of Zoliflodacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Bacteria microscopic: Follow up | 1 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Erythrocytes microscopic: Follow up | 2 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Erythrocytes microscopic: 24 hour post dose | 2 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Leukocytes microscopic: Follow up | 1 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Glucose dipstick: Follow up | 0 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Glucose dipstick: 24 hour post dose | 0 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Protein dipstick: Follow up | 0 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Leukocytes microscopic: 24 hour post dose | 0 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Occult blood dipstick: 24 hour post dose | 5 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Bacteria microscopic: 24 hour post dose | 2 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Bacteria microscopic: Follow up | 2 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Occult blood dipstick: Follow up | 0 Participants |
| Placebo | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Protein dipstick: 24 hour post dose | 0 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Occult blood dipstick: Follow up | 1 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Erythrocytes microscopic: 24 hour post dose | 3 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Glucose dipstick: Follow up | 0 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Bacteria microscopic: 24 hour post dose | 2 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Erythrocytes microscopic: Follow up | 2 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Leukocytes microscopic: 24 hour post dose | 2 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Protein dipstick: Follow up | 1 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Bacteria microscopic: Follow up | 0 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Leukocytes microscopic: Follow up | 0 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Glucose dipstick: 24 hour post dose | 0 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Protein dipstick: 24 hour post dose | 0 Participants |
| 400 mg of Moxifloxacin | Occurrence of Urinalysis Adverse Events Following Administration of Study Product | Occult blood dipstick: 24 hour post dose | 3 Participants |
Secondary
Relationship Between Plasma Concentrations of Zoliflodacin and Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin
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
Population: Any participants who received study product and had post dose assessments.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 2 g of Zoliflodacin | Relationship Between Plasma Concentrations of Zoliflodacin and Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin | 1.5 milliseconds (msec) |
| 4 g of Zoliflodacin | Relationship Between Plasma Concentrations of Zoliflodacin and Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin | 3.0 milliseconds (msec) |
Secondary
Terminal Elimination Half-life (t1/2) of Zoliflodacin
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 g of Zoliflodacin | Terminal Elimination Half-life (t1/2) of Zoliflodacin | 5.55 Hour | Standard Deviation 0.67 |
| 4 g of Zoliflodacin | Terminal Elimination Half-life (t1/2) of Zoliflodacin | 5.99 Hour | Standard Deviation 0.71 |
Secondary
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
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
Population: Any participants who received a dose of moxifloxacin and placebo and had post dose assessments is counted in the population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 2 g of Zoliflodacin | 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 | 1 hour post dose | 7.9 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 2 hour post dose | 8.5 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 3 hour post dose | 8.0 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 4 hour post dose | 7.2 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 4 hour post dose | -3.3 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 1 hour post dose | -2.3 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 3 hour post dose | -2.6 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 2 hour post dose | -2.2 milliseconds (msec) |
Comparison: 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.
Comparison: 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.
Comparison: 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.
Comparison: 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.
Secondary
Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 3 hour post dose | 2.2 beats/minute |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 24 hour post dose | 2.5 beats/minute |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 6 hour post dose | 9.4 beats/minute |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 4 hour post dose | 1.6 beats/minute |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 0.5 hour post dose | 0.4 beats/minute |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 12 hour post dose | 10.6 beats/minute |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 2 hour post dose | 1.0 beats/minute |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 1 hour post dose | 1.6 beats/minute |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 8 hour post dose | 8.7 beats/minute |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 4 hour post dose | 3.7 beats/minute |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 0.5 hour post dose | 2.2 beats/minute |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 1 hour post dose | 2.3 beats/minute |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 2 hour post dose | 3.6 beats/minute |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 3 hour post dose | 4.5 beats/minute |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 6 hour post dose | 10.0 beats/minute |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 8 hour post dose | 8.3 beats/minute |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 12 hour post dose | 10.4 beats/minute |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 24 hour post dose | 2.8 beats/minute |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 2 hour post dose | 0.1 beats/minute |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 0.5 hour post dose | 0.1 beats/minute |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 8 hour post dose | 5.8 beats/minute |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 1 hour post dose | -0.6 beats/minute |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 24 hour post dose | 3.4 beats/minute |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 4 hour post dose | 0.00 beats/minute |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 3 hour post dose | 0.7 beats/minute |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 12 hour post dose | 9.7 beats/minute |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin | 6 hour post dose | 7.8 beats/minute |
Secondary
Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 3 hour post dose | -0.4 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 24 hour post dose | -0.5 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 6 hour post dose | 0.1 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 4 hour post dose | -0.5 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 0.5 hour post dose | -0.3 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 12 hour post dose | -0.4 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 2 hour post dose | -0.6 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 1 hour post dose | -0.5 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 8 hour post dose | -0.7 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 4 hour post dose | -0.2 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 0.5 hour post dose | -0.1 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 1 hour post dose | 0.1 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 2 hour post dose | -0.5 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 3 hour post dose | -0.4 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 6 hour post dose | 0.1 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 8 hour post dose | -0.7 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 12 hour post dose | -0.5 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 24 hour post dose | -0.2 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 2 hour post dose | 0.0 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 0.5 hour post dose | -0.3 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 8 hour post dose | -0.3 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 1 hour post dose | 0.0 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 24 hour post dose | -0.4 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 4 hour post dose | -0.1 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 3 hour post dose | -0.1 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 12 hour post dose | -0.3 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin | 6 hour post dose | 0.8 milliseconds (msec) |
Secondary
Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 3 hour post dose | -32.0 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 24 hour post dose | -37.4 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 6 hour post dose | -127.1 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 4 hour post dose | -23.3 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 0.5 hour post dose | -5.8 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 12 hour post dose | -141.2 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 2 hour post dose | -13.8 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 1 hour post dose | -22.6 milliseconds (msec) |
| 2 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 8 hour post dose | -120.2 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 4 hour post dose | -47.6 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 0.5 hour post dose | -33.5 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 1 hour post dose | -35.0 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 2 hour post dose | -51.0 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 3 hour post dose | -63.1 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 6 hour post dose | -133.0 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 8 hour post dose | -111.0 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 12 hour post dose | -139.8 milliseconds (msec) |
| 4 g of Zoliflodacin | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 24 hour post dose | -41.2 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 2 hour post dose | 3.0 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 0.5 hour post dose | -1.2 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 8 hour post dose | -87.5 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 1 hour post dose | 9.7 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 24 hour post dose | -50.2 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 4 hour post dose | -0.7 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 3 hour post dose | -10.1 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 12 hour post dose | -140.5 milliseconds (msec) |
| Placebo | Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin | 6 hour post dose | -113.7 milliseconds (msec) |
Secondary
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
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 2 g of Zoliflodacin | 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 | 3 hour post dose | -2.6 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 24 hour post dose | -1.7 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 6 hour post dose | -3.6 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 4 hour post dose | -2.8 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 0.5 hour post dose | -0.7 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 12 hour post dose | -3.0 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 2 hour post dose | -1.6 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 1 hour post dose | -0.9 milliseconds (msec) |
| 2 g of Zoliflodacin | 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 | 8 hour post dose | -5.7 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 4 hour post dose | -3.2 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 0.5 hour post dose | -1.1 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 1 hour post dose | -2.3 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 2 hour post dose | -1.8 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 3 hour post dose | -2.9 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 6 hour post dose | -3.9 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 8 hour post dose | -5.4 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 12 hour post dose | -3.5 milliseconds (msec) |
| 4 g of Zoliflodacin | 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 | 24 hour post dose | -0.8 milliseconds (msec) |
| Placebo | 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 | 2 hour post dose | -0.2 milliseconds (msec) |
| Placebo | 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 | 0.5 hour post dose | -0.3 milliseconds (msec) |
| Placebo | 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 | 8 hour post dose | -5.3 milliseconds (msec) |
| Placebo | 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 | 1 hour post dose | 0.2 milliseconds (msec) |
| Placebo | 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 | 24 hour post dose | -0.7 milliseconds (msec) |
| Placebo | 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 | 4 hour post dose | -0.6 milliseconds (msec) |
| Placebo | 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 | 3 hour post dose | -1.1 milliseconds (msec) |
| Placebo | 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 | 12 hour post dose | -4.3 milliseconds (msec) |
| Placebo | 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 | 6 hour post dose | -1.8 milliseconds (msec) |
Secondary
Time of Maximum Observed Concentration (Tmax) of Zoliflodacin
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 g of Zoliflodacin | Time of Maximum Observed Concentration (Tmax) of Zoliflodacin | 2.90 hour | Standard Deviation 1.08 |
| 4 g of Zoliflodacin | Time of Maximum Observed Concentration (Tmax) of Zoliflodacin | 3.03 hour | Standard Deviation 2.05 |