Thorough QT/QTC (TQT) Clinical Trial to Evaluate the Effect of Zoliflodacin on Cardiac Repolarization in Healthy Male and Female Subjects
Condition: Electrocardiogram Repolarisation Abnormality; Gonococcal Infection
MeSH terms: Gonorrhea
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): AZD0914; Moxifloxacin; Placebo
Intervention type(s): Drug; Drug; Other
Intervention description(s): 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.; 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.; 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.
Intervention MeSH terms: Moxifloxacin; Zoliflodacin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: AZD0914; Cardiac; ETX0914; Healthy; Moxifloxacin; Repolarization; Study; TQT; Volunteers; Zoliflodacin