Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations.
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 A(2A) 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.
Hauser
Robert A
RA
Department of Neurology, University of South Florida, Tampa, Florida 33606, USA. rhauser@health.usf.edu
Shulman
Lisa M
LM
Trugman
Joel M
JM
Roberts
John W
JW
Mori
Akihisa
A
Ballerini
Rocco
R
Sussman
Neil M
NM
D000368:Aged; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology; D011687:Purines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors
D000978:Antiparkinson Agents; D011687:Purines; C111599:istradefylline; D007980:Levodopa