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See the Appendix on page 303 for a list of Group members.
From the Departments of Neurology, Pharmacology, and Experimental Therapeutics (Dr. Hauser), University of South Florida, and Tampa General Healthcare; Department of Neurology (Dr. Hubble), Ohio State University, Columbus; and Parkinson’s and Movement Disorder Institute (Dr. Truong), Fountain Valley, CA.
Address correspondence and reprint requests to Dr. R.A. Hauser, Parkinson’s Disease and Movement Disorders Center, University of South Florida and Tampa General Healthcare, 4 Columbia Dr., Suite 410, Tampa, FL 33606; e-mail: rhauser{at}hsc.usf.edu
Objective: To evaluate the safety and efficacy of the adenosine A2A receptor antagonist istradefylline (KW-6002) in patients with levodopa-treated Parkinson’s disease (PD) with both motor fluctuations and peak-dose dyskinesias.
Methods: This was a 12-week, double-blind, randomized, placebo-controlled, exploratory study in which PD subjects with both motor fluctuations and peak-dose dyskinesias were randomized to treatment with placebo (n = 29), istradefylline up to 20 mg/day (n = 26), or istradefylline up to 40 mg/day (n = 28). There was no prespecified primary outcome measure, and 19 outcome variables were analyzed.
Results: As assessed by home diaries, subjects assigned to istradefylline experienced a mean (± SE) reduction in the proportion of awake time spent in the "off" state of 7.1 ± 2.0% compared with an increase of 2.2 ± 2.7% in the placebo group (p = 0.008). There was a decrease in "off" time of 1.2 ± 0.3 hours in the istradefylline group compared with an increase of 0.5 ± 0.5 hour in the placebo group (p = 0.004). Dyskinesia severity was unchanged, but "on" time with dyskinesia increased in the istradefylline group compared with the placebo group (percent, p = 0.002; hours, p = 0.001). No differences were observed in change in Unified Parkinson’s Disease Rating Scale scores or Clinical Global Impression of Change. Twenty-four percent of placebo-assigned subjects and 20% of istradefylline-assigned subjects withdrew from the study. Both dose regimens of istradefylline were generally well tolerated, and nausea was the most common adverse event.
Conclusion: Istradefylline was generally well tolerated and reduced "off" time as assessed by home diaries. Severity of dyskinesia was unchanged, but "on" time with dyskinesia increased.
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