title: Effect of pomaglumetad methionil on the QT interval in subjects with schizophrenia.
abstract: OBJECTIVE
  This thorough QT/QTc (TQT) study assessed the effects of a supratherapeutic dose of pomaglumetad methionil, a potential treatment for schizophrenia, compared to placebo on the QT interval in subjects with schizophrenia.
  
  
  METHODS
  This double-blind, 3-period crossover study enrolled 86 subjects aged 22 - 63 years, who met Diagnostic and Statistical Manual, Fourth Edition, Test Revision (DSM-IV-TR) criteria for schizophrenia; 78 subjects completed the study. Subjects were randomly assigned to sequences of 3 treatment periods of single oral doses of pomaglumetad methionil 400 mg, moxifloxacin 400 mg, and placebo. Quadruplicate electrocardiograms (ECGs) were extracted from 2 hours predose to 12 hours postdose and were overread by a blinded central reader. Time-matched pharmacokinetic (PK) parameters were assessed.
  
  
  RESULTS
  At all-time points, the upper bound of the 90% 2-sided confidence interval (CI) for the least squares (LS) mean difference in changes from baseline in Fridericia's corrected QT interval (ΔQTcF) between pomaglumetad methionil and placebo was < 10 milliseconds (msec). Sufficient assay sensitivity was not achieved, likely due to food effect; although the maximum observed drug concentration (Cmax) with moxifloxacin (1,410 ng/mL) was lower than expected, the slope of the regression line of moxifloxacin plasma concentrations versus placebo-subtracted ΔQTcF was similar to that reported in the literature.
  
  
  CONCLUSIONS
  A single supratherapeutic dose of 400 mg pomaglumetad methionil did not prolong QTcF to a clinically significant degree and, importantly, did not result in any absolute QTcF > 450 msec or increase in QTcF from predose > 30 msec.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Malcolm I
authors.initials: MI
authors.lastname: Mitchell
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: Knadler
authors.forename: Amanda
authors.initials: A
authors.lastname: Long
authors.forename: Jennifer
authors.initials: J
authors.lastname: Witcher
authors.forename: David
authors.initials: D
authors.lastname: Walling
authors.forename: William
authors.initials: W
authors.lastname: Annes
authors.forename: Mosun
authors.initials: M
authors.lastname: Ayan-Oshodi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000596:Amino Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016903:Drug Monitoring; D004562:Electrocardiography; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018570:Risk Assessment; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000596:Amino Acids; D018690:Excitatory Amino Acid Agonists; C534551:LY 2140023; D011355:Prodrugs