title: A Phase 1, double-blind, 4-period crossover study to investigate the effects of pomalidomide on QT interval in healthy male subjects.
abstract: OBJECTIVE
  Pomalidomide is a distinct immunomodulatory agent approved for the treatment of relapsed and refractory multiple myeloma. QT interval was monitored in prior studies, and although there was no indication that pomalidomide could induce QT prolongation, a formal analysis was not previously conducted. Therefore, we present here the results of a study evaluating the effects of pomalidomide on QT interval corrected for heart rate (QTc) using Fridericia's formula (QTcF) and other electrocardiogram (ECG) parameters.
  
  
  METHODS
  Healthy male volunteers with normal or clinically acceptable laboratory tests and ECG results were randomized to receive single oral doses of placebo, pomalidomide 4 mg, pomalidomide 20 mg, and moxifloxacin 400 mg (positive control) in different sequences. Subjects were evaluated by digital ECG monitoring and underwent blood sampling and standard safety monitoring.
  
  
  RESULTS
  Seventy-two subjects were enrolled. In ECG evaluations performed after dosing with pomalidomide 4 mg (therapeutic dose) or 20 mg (supratherapeutic dose), the upper limit of the two-sided 90 % CI for mean change from baseline and placebo-corrected QTcF was <10 ms at all postdose time points, which is below the defined threshold of regulatory concern. In contrast, moxifloxacin induced a clear prolongation in QT interval. Changes in heart rate and other ECG parameters after pomalidomide dosing were clinically insignificant.
  
  
  CONCLUSIONS
  Pomalidomide given as a single oral dose of up to 20 mg was not associated with QT prolongation in healthy male subjects.
authors.affiliation: PPD Phase 1 Clinic, Austin, TX, USA.
authors.forename: Sabiha A
authors.initials: SA
authors.lastname: Mondal
authors.affiliation: Celgene Corporation, 86 Morris Avenue, Summit, NJ, 07901, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Assaf
authors.affiliation: Celgene Corporation, 86 Morris Avenue, Summit, NJ, 07901, USA.
authors.forename: Liangang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Celgene Corporation, 86 Morris Avenue, Summit, NJ, 07901, USA. omara_edward@yahoo.com.
authors.forename: Edward
authors.initials: E
authors.lastname: O'Mara
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects; D064368:Healthy Volunteers; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D000077266:Moxifloxacin; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D013792:Thalidomide; C467566:pomalidomide; D000077266:Moxifloxacin
keywords: Immunomodulatory agent; Pharmacokinetics; Phase 1; Pomalidomide; QT interval; Safety