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Research Article| Volume 25, ISSUE 3, P642-649, March 2016

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Phosphodiesterase-5 Inhibitor PF-03049423 Effect on Stroke Recovery: A Double-Blind, Placebo-Controlled Randomized Clinical Trial

Published:December 28, 2015DOI:https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.11.026
Phosphodiesterase-5 Inhibitor PF-03049423 Effect on Stroke Recovery: A Double-Blind, Placebo-Controlled Randomized Clinical Trial
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      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.

      Key Words

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      Article info

      Publication history

      Published online: December 28, 2015
      Accepted: November 22, 2015
      Received in revised form: October 14, 2015
      Received: June 17, 2015

      Footnotes

      Grant support: The study was sponsored and financed by Pfizer.

      Disclosure of conflicts of interest: Jessica Mancuso, Phil Woodward, Martin Bednar, and Peter Loudon are employed by Pfizer; Franco Di Cesare, Leoben Research Ltd, provided medical and scientific consulting services that were funded by Pfizer.

      The A9541004 Stroke Study Investigators Group: Bulgaria: Prof. Staykov, Dr. Petrova, Prof. Penkov Daskalov, Prof. Paraskeva Kostova Stamenova, Prof. Tsvetanov Georgiev, Dr. Naydenov; Canada: Dr. Siddiqui; Czech Republic: Dr. Mikulik, Dr. Polivka; France: Prof. Sibon, Prof. Samson; Germany: Prof. Weimar, Prof. Berrouschot, Dr. Hobohm, Dr. Ritter, Dr. Schlachetzki; Hungary: Dr. Szakacs, Dr. Panczel, Dr. Csanyi, Dr. Szabo, Dr. Ovary, Dr. Debreczeni; India: Dr. Anand Alurkar, Dr. Puneet Agarwal; Republic of Korea: Dr. Sun Uck Kwon, Prof. Dr. Byung-Woo Yoon, Dr. Kwang Ho Lee, Dr. Ji Hoe Heo, Dr. Hee-Joon Bae, Dr. Joung-Ho Rha, Dr. Joon-Tae Kim, Dr. Byung-Chul Lee; Taiwan: Dr. Jiann-Shing Jeng, Dr. Tsong-Hai Lee, Dr. Chung-Hsiang Liu, Dr. Chia-Wei Liou; United States: Dr. Fen-Lei Finland Chang, Dr. Jin-Moo Lee, Dr. Reichwein, Dr. Huang, Dr. Singhal, Dr. Chiu, Dr. Harris.

      Identification

      DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.11.026

      Copyright

      © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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