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 (

CLINICAL TRIAL REGISTRATION INFORMATION:

http://www.clinicaltrials.gov, unique identifier: NCT01208233; http://www.clinicaltrialsregister.eu, EudraCT number: 2010-021414-32).

MATERIALS AND 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: Franco Di Cesare, Jessica Mancuso, Phil Woodward, Martin M Bednar, Peter T Loudon, A9541004 Stroke Study Group
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 25 Issue 3 Pg. 642-9 (Mar 2016) ISSN: 1532-8511 [Electronic] United States
• PMID: 26738812 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• 3-(4-(2-hydroxyethyl)piperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido(3,4-b)pyrazin-2(1H)-one
• Neuroprotective Agents
• Phosphodiesterase 5 Inhibitors
• Pyrazines
• Pyridines

Topics

• Adult
• Aged
• Aged, 80 and over
• Double-Blind Method
• Female
• Humans
• International Cooperation
• Male
• Middle Aged
• Neuroprotective Agents (therapeutic use)
• Phosphodiesterase 5 Inhibitors (therapeutic use)
• Pyrazines (therapeutic use)
• Pyridines (therapeutic use)
• Severity of Illness Index
• Stroke (drug therapy)
• Time Factors