title: Phosphodiesterase-5 Inhibitor PF-03049423 Effect on Stroke Recovery: A Double-Blind, Placebo-Controlled Randomized Clinical Trial.
abstract: BACKGROUND
  The therapeutic potential of phosphodiesterase-5 inhibitor PF-03049423 was evaluated in a phase 2, multicenter, randomized, double-blind, placebo-controlled study of subjects with acute ischemic stroke (
  
  
  BACKGROUND
  http://www.clinicaltrials.gov, unique identifier: NCT01208233; http://www.clinicaltrialsregister.eu, EudraCT number: 2010-021414-32).
  
  
  METHODS
  Subjects (N = 70) received PF-03049423 6 mg (or placebo, N = 67) once daily, orally, commencing between 24 and 78 hours of stroke onset, and continuing for 90 days. Postbaseline efficacy assessments were performed on Days 7, 14, 30, 60, and 90. Modified Rankin Scale (mRS), Barthel Index, National Institutes of Health Stroke Scale, Box and Blocks Test, Hand-Grip Strength Test, 10-Meter Walk Test, Repeatable Battery Assessment of Neuropsychological Status Naming and Coding Subtests, Line Cancellation Test, and Recognition Memory Test were administered to evaluate poststroke recovery. The primary endpoint was the mRS responder rate (score 0-2 at Day 90). The study included a planned interim analysis of efficacy data.
  
  
  RESULTS
  The primary efficacy analysis using logistic regression showed no statistically significant difference between PF-03049423 6 mg and placebo (responder rate of 42.6% and 46.2%, respectively). Although PF-03049423 showed a satisfactory safety and tolerability profile, no signal of efficacy emerged from any of the outcome measures.
  
  
  CONCLUSIONS
  PF-03049423 showed no therapeutic potential for acute ischemic stroke.
authors.affiliation: Leoben Research Limited, Glasgow, United Kingdom.
authors.forename: Franco
authors.initials: F
authors.lastname: Di Cesare
authors.affiliation: Research Statistics, Pfizer, Groton, CT.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mancuso
authors.affiliation: Research Statistics, Pfizer, Cambridge, United Kingdom.
authors.forename: Phil
authors.initials: P
authors.lastname: Woodward
authors.affiliation: Neuroscience and Pain Research Unit, Pfizer, Cambridge, MA.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Bednar
authors.affiliation: Neuroscience and Pain Research Unit, Pfizer, Cambridge, United Kingdom. Electronic address: peter.t.loudon@Pfizer.com.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Loudon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy*; D013997:Time Factors
chemical_list: C549061:3-(4-(2-hydroxyethyl)piperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido(3,4-b)pyrazin-2(1H)-one; D018696:Neuroprotective Agents; D058986:Phosphodiesterase 5 Inhibitors; D011719:Pyrazines; D011725:Pyridines
keywords: PDE5; Stroke; clinical trial; neurorestoration