OBJECTIVE: To evaluate the safety and efficacy of the adenosine A(2A) 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.
RCT Entities:
OBJECTIVE: To evaluate the safety and efficacy of the adenosine A(2A) 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.
Authors: K Fuxe; D Marcellino; D O Borroto-Escuela; M Guescini; V Fernández-Dueñas; S Tanganelli; A Rivera; F Ciruela; L F Agnati Journal: CNS Neurosci Ther Date: 2010-03-16 Impact factor: 5.243
Authors: Kjell Fuxe; Sergi Ferré; Meritxell Canals; Maria Torvinen; Anton Terasmaa; Daniel Marcellino; Steven R Goldberg; William Staines; Kirsten X Jacobsen; Carmen Lluis; Amina S Woods; Luigi F Agnati; Rafael Franco Journal: J Mol Neurosci Date: 2005 Impact factor: 3.444
Authors: K Fuxe; M Canals; M Torvinen; D Marcellino; A Terasmaa; S Genedani; G Leo; D Guidolin; Z Diaz-Cabiale; A Rivera; L Lundstrom; U Langel; J Narvaez; S Tanganelli; C Lluis; S Ferré; A Woods; R Franco; L F Agnati Journal: J Neural Transm (Vienna) Date: 2006-10-27 Impact factor: 3.575
Authors: S Ferré; I Diamond; S R Goldberg; L Yao; S M O Hourani; Z L Huang; Y Urade; I Kitchen Journal: Prog Neurobiol Date: 2007-05-01 Impact factor: 11.685