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

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ClinicalTrials.gov Identifier: NCT03613649
Recruitment Status : Completed
First Posted : August 3, 2018
Last Update Posted : May 10, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE July 26, 2018
First Posted Date  ICMJE August 3, 2018
Last Update Posted Date May 10, 2019
Actual Study Start Date  ICMJE September 25, 2018
Actual Primary Completion Date January 2, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
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 [ Time Frame: Day 1 through Day 26 ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 1, 2018)
  • The upper bound of the one-sided 95% confidence interval (CI) for the largest time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin is < 10 msec [ Time Frame: Day 1 to Day 2 ]
  • The upper bound of the one-sided 95% confidence interval (CI) for the largest time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin is < 10 msec [ Time Frame: Day 17 to Day 18 ]
  • The upper bound of the one-sided 95% confidence interval (CI) for the largest time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin is < 10 msec [ Time Frame: Day 25 to Day 26 ]
  • The upper bound of the one-sided 95% confidence interval (CI) for the largest time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin is < 10 msec [ Time Frame: Day 9 to Day 10 ]
  • The upper bound of the one-sided 95% confidence interval (CI) for the largest time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin is < 10 msec [ Time Frame: Day 1 to Day 2 ]
  • The upper bound of the one-sided 95% confidence interval (CI) for the largest time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin is < 10 msec [ Time Frame: Day 17 to Day 18 ]
  • The upper bound of the one-sided 95% confidence interval (CI) for the largest time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin is < 10 msec [ Time Frame: Day 25 to Day 26 ]
  • The upper bound of the one-sided 95% confidence interval (CI) for the largest time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin is < 10 msec [ Time Frame: Day 9 to Day 10 ]
Change History Complete list of historical versions of study NCT03613649 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
  • Incidence of abnormal T-wave morphology following administration of zoliflodacin [ Time Frame: Up to 24 hours after dosing ]
  • Occurrence of treatment-emergent serious adverse events (SAEs) and other unsolicited treatment-emergent AEs, including AE-graded changes in vital signs, clinical labs, and ECG following administration of zoliflodacin and moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Relationship between plasma concentrations of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) following administration of zoliflodacin [ Time Frame: Up to 24 hours after dosing ]
  • Single-dose plasma concentrations of zoliflodacin [ Time Frame: Up to 24 hours after dosing ]
  • 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 [ Time Frame: Up to 4 hours after dosing ]
  • Time-matched, placebo-corrected, baseline-adjusted heart rate (HR) following administration of zoliflodacin [ Time Frame: Up to 24 hours after dosing ]
  • Time-matched, placebo-corrected, baseline-adjusted PR interval following administration of zoliflodacin [ Time Frame: Up to 24 hours after dosing ]
  • Time-matched, placebo-corrected, baseline-adjusted QRS interval following administration of zoliflodacin [ Time Frame: Up to 24 hours after dosing ]
  • Time-matched, placebo-corrected, baseline-adjusted RR interval following administration of zoliflodacin [ Time Frame: Up to 24 hours after dosing ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2018)
  • Apparent oral clearance (CL/F) of zoliflodacin after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Apparent oral clearance (CL/F) of zoliflodacin after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Apparent volume of distribution (Vz/F) of zoliflodacin after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Apparent volume of distribution (Vz/F) of zoliflodacin after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Area under the concentration time-curve from time zero to infinity (AUC(0-infinity)) of zoliflodacin after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Area under the concentration time-curve from time zero to infinity (AUC(0-infinity)) of zoliflodacin after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Area under the concentration time-curve from time zero to the last concentration above the lower limit of quantitation (AUC(0-last)) of zoliflodacin after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Area under the concentration time-curve from time zero to the last concentration above the lower limit of quantitation (AUC(0-last)) of zoliflodacin after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Area under the concentration time-curve from time zero to time t (AUC(0-t)) of zoliflodacin after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Area under the concentration time-curve from time zero to time t (AUC(0-t)) of zoliflodacin after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Change in alanine transferase (ALT) from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in alanine transferase (ALT) from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in alanine transferase (ALT) from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in albumin from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in albumin from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in albumin from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in alkaline phosphatase from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in alkaline phosphatase from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in alkaline phosphatase from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in aspartate transferase (AST) from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in aspartate transferase (AST) from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in aspartate transferase (AST) from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in basophil count from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in basophil count from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in basophil count from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in bicarbonate (CO2) level from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in bicarbonate (CO2) level from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in bicarbonate (CO2) level from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in blood urea nitrogen (BUN) from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in blood urea nitrogen (BUN) from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in blood urea nitrogen (BUN) from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in calcium level from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in calcium level from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in calcium level from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in chloride level from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in chloride level from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in chloride level from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in diastolic blood pressure from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in diastolic blood pressure from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in diastolic blood pressure from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in direct bilirubin from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in direct bilirubin from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in direct bilirubin from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in eosinophil count from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in eosinophil count from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in eosinophil count from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in fasting glucose from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in fasting glucose from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in fasting glucose from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in hematocrit (Hct) from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in hematocrit (Hct) from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in hematocrit (Hct) from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in hemoglobin (Hgb) from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in hemoglobin (Hgb) from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in hemoglobin (Hgb) from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in HR from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in HR from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in HR from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in lymphocyte count from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in lymphocyte count from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in lymphocyte count from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in magnesium level from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in magnesium level from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in magnesium level from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in monocyte count from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in monocyte count from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in monocyte count from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in neutrophil count from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in neutrophil count from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in neutrophil count from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in oral temperature from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in oral temperature from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in oral temperature from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in phosphorous level from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in phosphorous level from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in phosphorous level from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in platelet count from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in platelet count from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in platelet count from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in potassium level from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in potassium level from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in potassium level from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in PR interval from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in PR interval from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in PR interval from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in pulse rate from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in pulse rate from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in pulse rate from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in QRS interval from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in QRS interval from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in QRS interval from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in QT interval from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in QT interval from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in QT interval from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in QTcF interval from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in QTcF interval from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in QTcF interval from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in red blood cell (RBC) count from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in red blood cell (RBC) count from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in red blood cell (RBC) count from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in red blood cells (RBCs) in urine (sediment) from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in red blood cells (RBCs) in urine (sediment) from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in red blood cells (RBCs) in urine (sediment) from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in respiratory rate from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in respiratory rate from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in respiratory rate from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in RR interval from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in RR interval from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in RR interval from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in serum creatinine, with estimation of glomerular filtration rate (GFR), from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in serum creatinine, with estimation of glomerular filtration rate (GFR), from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in serum creatinine, with estimation of glomerular filtration rate (GFR), from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in sodium level from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in sodium level from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in sodium level from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in systolic blood pressure from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in systolic blood pressure from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in systolic blood pressure from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in total bilirubin from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in total bilirubin from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in total bilirubin from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in total protein from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in total protein from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in total protein from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in urine bacteria from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in urine bacteria from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in urine bacteria from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in urine crystals from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in urine crystals from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in urine crystals from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in urine hyaline casts from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in urine hyaline casts from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in urine hyaline casts from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in white blood cell (WBC) count from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in white blood cell (WBC) count from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in white blood cell (WBC) count from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Change in white blood cells (WBCs) in urine (sediment) from baseline following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in white blood cells (WBCs) in urine (sediment) from baseline following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Change in white blood cells (WBCs) in urine (sediment) from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Elimination rate constant (Ke) of zoliflodacin after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Elimination rate constant (Ke) of zoliflodacin after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Incidence of biphasic T-waves after 2 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of biphasic T-waves after 2 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of biphasic T-waves after 2 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of biphasic T-waves after 2 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Incidence of biphasic T-waves after 4 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of biphasic T-waves after 4 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of biphasic T-waves after 4 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of biphasic T-waves after 4 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Incidence of flat T-waves after 2 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of flat T-waves after 2 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of flat T-waves after 2 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of flat T-waves after 2 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Incidence of flat T-waves after 4 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of flat T-waves after 4 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of flat T-waves after 4 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of flat T-waves after 4 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Incidence of normal T-waves (-) after 2 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of normal T-waves (-) after 2 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of normal T-waves (-) after 2 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of normal T-waves (-) after 2 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Incidence of normal T-waves (-) after 4 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of normal T-waves (-) after 4 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of normal T-waves (-) after 4 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of normal T-waves (-) after 4 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Incidence of notched T-waves (+) after 2 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of notched T-waves (+) after 2 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of notched T-waves (+) after 2 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of notched T-waves (+) after 2 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Incidence of notched T-waves (+) after 4 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of notched T-waves (+) after 4 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of notched T-waves (+) after 4 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of notched T-waves (+) after 4 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Incidence of notched T-waves (-) after 2 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of notched T-waves (-) after 2 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of notched T-waves (-) after 2 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of notched T-waves (-) after 2 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Incidence of notched T-waves (-) after 4 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Incidence of notched T-waves (-) after 4 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Incidence of notched T-waves (-) after 4 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Incidence of notched T-waves (-) after 4 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Maximum observed concentration (Cmax) of zoliflodacin after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Maximum observed concentration (Cmax) of zoliflodacin after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Occurrence of blood in urine following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of blood in urine following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of blood in urine following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of clinically significant ECG abnormalities following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of clinically significant ECG abnormalities following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of clinically significant ECG abnormalities following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of glucose in urine following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of glucose in urine following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of glucose in urine from baseline following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of protein in urine following administration of 2 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of protein in urine following administration of 4 g zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of protein in urine following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of treatment-emergent serious adverse events (SAEs) following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of treatment-emergent serious adverse events (SAEs) following administration of zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of unsolicited treatment-emergent adverse events (AEs) following administration of moxifloxacin [ Time Frame: Day 1 through Day 32 ]
  • Occurrence of unsolicited treatment-emergent adverse events (AEs) following administration of zoliflodacin [ Time Frame: Day 1 through Day 32 ]
  • Relationship between apparent oral clearance (CL/F) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between apparent oral clearance (CL/F) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between apparent volume of distribution (Vz/F) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between apparent volume of distribution (Vz/F) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between area under concentration time-curve from time zero to infinity (AUC(0-infinity)) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between area under concentration time-curve from time zero to infinity (AUC(0-infinity)) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between area under concentration time-curve from time zero to last concentration above lower limit of quantitation (AUC(0-last)) zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval after 2 g zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between area under concentration time-curve from time zero to last concentration above lower limit of quantitation (AUC(0-last)) zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval after 4 g zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between area under concentration time-curve from time zero to time t (AUC(0-t)) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between area under concentration time-curve from time zero to time t (AUC(0-t)) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between elimination rate constant (Ke) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between elimination rate constant (Ke) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between maximum observed concentration (Cmax) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between maximum observed concentration (Cmax) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between terminal elimination half-life (t1/2) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between terminal elimination half-life (t1/2) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between time of maximum observed concentration (Tmax) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Relationship between time of maximum observed concentration (Tmax) of zoliflodacin and time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Terminal elimination half-life (t1/2) of zoliflodacin after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Terminal elimination half-life (t1/2) of zoliflodacin after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • The lower bound of the one-sided 95% confidence interval (CI) of the time-matched, placebo-corrected, baseline-adjusted mean QTcF interval (delta delta QTcF) is > 5 msec after a single dose of moxifloxacin 400 mg [ Time Frame: 1 hour to 4 hours after dosing ]
  • Time of maximum observed concentration (Tmax) of zoliflodacin after 2 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Time of maximum observed concentration (Tmax) of zoliflodacin after 4 g dose of zoliflodacin [ Time Frame: From 0.5h before dosing to 24h after dosing ]
  • Time-matched, placebo-corrected, baseline-adjusted HR collected after 2 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Time-matched, placebo-corrected, baseline-adjusted HR collected after 2 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Time-matched, placebo-corrected, baseline-adjusted HR collected after 2 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Time-matched, placebo-corrected, baseline-adjusted HR collected after 2 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Time-matched, placebo-corrected, baseline-adjusted HR collected after 4 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Time-matched, placebo-corrected, baseline-adjusted HR collected after 4 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Time-matched, placebo-corrected, baseline-adjusted HR collected after 4 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Time-matched, placebo-corrected, baseline-adjusted HR collected after 4 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Time-matched, placebo-corrected, baseline-adjusted PR interval after 2 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Time-matched, placebo-corrected, baseline-adjusted PR interval after 2 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Time-matched, placebo-corrected, baseline-adjusted PR interval after 2 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Time-matched, placebo-corrected, baseline-adjusted PR interval after 2 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Time-matched, placebo-corrected, baseline-adjusted PR interval after 4 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Time-matched, placebo-corrected, baseline-adjusted PR interval after 4 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Time-matched, placebo-corrected, baseline-adjusted PR interval after 4 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Time-matched, placebo-corrected, baseline-adjusted PR interval after 4 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Time-matched, placebo-corrected, baseline-adjusted QRS interval after 2 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Time-matched, placebo-corrected, baseline-adjusted QRS interval after 2 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Time-matched, placebo-corrected, baseline-adjusted QRS interval after 2 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Time-matched, placebo-corrected, baseline-adjusted QRS interval after 2 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Time-matched, placebo-corrected, baseline-adjusted QRS interval after 4 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Time-matched, placebo-corrected, baseline-adjusted QRS interval after 4 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Time-matched, placebo-corrected, baseline-adjusted QRS interval after 4 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Time-matched, placebo-corrected, baseline-adjusted QRS interval after 4 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Time-matched, placebo-corrected, baseline-adjusted RR interval after 2 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Time-matched, placebo-corrected, baseline-adjusted RR interval after 2 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Time-matched, placebo-corrected, baseline-adjusted RR interval after 2 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Time-matched, placebo-corrected, baseline-adjusted RR interval after 2 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
  • Time-matched, placebo-corrected, baseline-adjusted RR interval after 4 g dose of zoliflodacin [ Time Frame: Day 1 to Day 2 ]
  • Time-matched, placebo-corrected, baseline-adjusted RR interval after 4 g dose of zoliflodacin [ Time Frame: Day 17 to Day 18 ]
  • Time-matched, placebo-corrected, baseline-adjusted RR interval after 4 g dose of zoliflodacin [ Time Frame: Day 25 to Day 26 ]
  • Time-matched, placebo-corrected, baseline-adjusted RR interval after 4 g dose of zoliflodacin [ Time Frame: Day 9 to Day 10 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Thorough QT/QTC (TQT) Clinical Trial to Evaluate the Effect of Zoliflodacin on Cardiac Repolarization in Healthy Male and Female Subjects
Official Title  ICMJE A Phase 1, Randomized, Double-blinded, Four-period Crossover, Thorough QT/QTC (TQT) Clinical Trial to Evaluate the Effect of Zoliflodacin on Cardiac Repolarization in Healthy Male and Female Subjects
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE
  • Electrocardiogram Repolarisation Abnormality
  • Gonococcal Infection
Intervention  ICMJE
  • Drug: AZD0914
    Spiropyrimidinetrione antibacterial drug, which inhibits bacterial DNA synthesis by a novel mechanism. Powder will be reconstituted in 60 mL of tap water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin is taken, approximately 60 mL of tap water will be added to the cup and consumed by the subject to chase the initial dose.
  • Drug: Moxifloxacin
    Broad-spectrum 8-methoxy fluoroquinolone with activity against both Gram-positive and Gram-negative bacteria, including anaerobes. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride will be administered orally with 120 mL of tap water.
  • Other: Placebo
    Composed of 4 g of the same excipients found in zoliflodacin. Powder will be reconstituted in 60 mL of tap water and dosed orally after an overnight fast. After the cup containing 60 mL of placebo is taken, approximately 60 mL of tap water will be added to the cup and consumed by the subject to chase the initial dose.
Study Arms  ICMJE
  • Experimental: Treatment A
    2 g of zoliflodacin administered orally on Day 1 of each dosing period, n=72
    Intervention: Drug: AZD0914
  • Experimental: Treatment B
    4 g of zoliflodacin administered orally on Day 1 of each dosing period, n=72
    Intervention: Drug: AZD0914
  • Placebo Comparator: Treatment C
    Placebo for zoliflodacin administered orally on Day 1 of each dosing period, n=72
    Intervention: Other: Placebo
  • Active Comparator: Treatment D
    400 mg of moxifloxacin administered orally on Day 1 of each dosing period, n=72
    Intervention: Drug: Moxifloxacin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 1, 2018)
72
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2, 2019
Actual Primary Completion Date January 2, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03613649
Other Study ID Numbers  ICMJE 16-0110
HHSN272201500005I
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date May 7, 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP