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Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations§

Authors


  • Disclosures: Drs. Hauser, Shulman, Trugman and Roberts' institutions received compensation from Kyowa Pharmaceutical, Inc. for their sites' conduct of the study. Drs. Hauser, Shulman, and Trugman have received honoraria, and consulting fees from Kyowa Pharmaceutical, Inc. Dr. Mori is an employee of Kyowa Hakko Kogyo Co., Ltd. Drs. Ballerini and Sussman are employees of Kyowa Pharmaceutical, Inc. Since completion of the study, Dr. Trugman has become an employee of Forest Laboratories, Inc.

  • Non-sponsor Disclosures: Dr. Hauser has received honoraria or consulting fees from Bayer Schering Pharma AG, Bertek, Boehringer Ingelheim, Centopharm, Eisai Ltd, Genzyme, GlaxoSmithKline, Impax, Kyowa Pharmaceutical, Merck KgaA, Novartis, Ortho McNeil, Pfizer, Prestwick, Schwarz Pharma, Schering, Solvay, Teva Neuroscience, Valeant, and Vernalis. Dr. Trugman has received honoraria from GlaxoSmithKline. Dr. Shulman has received honoraria from Teva, Schwarz Pharma, and Boehringer Ingelheim.

  • §

    The authors have confirmed with the Editor that their work complies with the Journal's Editorial policy on ghost-writing. (Movement Disordres Vol. 20., No. 12, 2005, p. 1536).

  • Members of the group “Istradefy line 6002-US-013 study group” are listed as an Appendix

Abstract

The objective of this study was to evaluate the efficacy, safety, and tolerability of istradefylline 20 mg once daily versus placebo as an adjunct to levodopa in subjects with Parkinson's disease (PD) who have motor fluctuations. Istradefylline (KW-6002) is an adenosine A2A receptor antagonist that in primate models of PD improves motor function without causing or worsening dyskinesia. This 12-week, multicenter, double-blind, placebo-controlled, randomized, Phase 3 study of istradefylline was conducted in subjects experiencing an average daily OFF time of at least 3 hours (116 randomized to istradefylline; 115 to placebo). All were on stable levodopa regimens; 90% were also on stable regimens of other anti-Parkinson's medications. Istradefylline-treated subjects had significant placebo-corrected reductions in daily OFF time from baseline to endpoint: 4.6% (P = 0.03) and 0.7 hours (P = 0.03). For ON time with troublesome dyskinesia, the changes between istradefylline and placebo were not significant. Istradefylline was well tolerated, with 6 (5.2%) istradefylline-treated and 7 (6.1%) placebo-treated subjects withdrawing from the study because of adverse events. Dyskinesia, lightheadedness, tremor, constipation, and weight decrease were reported more often with istradefylline than placebo. We conclude that istradefylline is well tolerated and significantly reduces OFF time as an adjunct to levodopa in PD subjects with motor fluctuations. © 2008 Movement Disorder Society

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