Members of the 6002-US-005 Study Group are listed in the Appendix on page xx.
Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson's disease: A double-blind, randomized, multicenter clinical trial (6002-US-005)
Article first published online: 27 FEB 2008
Copyright © 2008 American Neurological Association
Annals of Neurology
Volume 63, Issue 3, pages 295–302, March 2008
How to Cite
LeWitt, P. A., Guttman, M., Tetrud, J. W., Tuite, P. J., Mori, A., Chaikin, P. and Sussman, N. M. (2008), Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson's disease: A double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol., 63: 295–302. doi: 10.1002/ana.21315
- Issue published online: 26 MAR 2008
- Article first published online: 27 FEB 2008
- Manuscript Accepted: 5 NOV 2007
- Manuscript Revised: 30 OCT 2007
- Manuscript Received: 6 SEP 2007
- Kyowa Pharmaceutical, Inc
Based on new understanding of nondopaminergic pathways involved in Parkinson's disease (PD) pathophysiology, a selective adenosine A2A receptor antagonist, istradefylline, shows promise for the treatment of PD.
Istradefylline (40mg/day) was studied in levodopa-treated PD subjects experiencing prominent wearing-off motor fluctuations. At 23 North American sites, 196 subjects were randomized in a double-blind, 12-week outpatient clinical trial of istradefylline (114 completing the trial) or placebo (58 completing the trial). The primary efficacy measure was change from baseline to end point in the percentage of daily awake “off” time, recorded by subjects using a patient PD diary. Secondary end points evaluated “on” time (including “on time with dyskinesia”), the Unified Parkinson's Disease Rating Scale, and a Clinical Global Impression–Improvement of Illness score. Clinical laboratory, electrocardiograms, vital signs, and adverse event monitoring comprised the safety monitoring.
After randomization, approximately 88% of subjects completed the double-blind period. Compared with baseline, the decrease of daily awake “off” time for istradefylline was a mean (± standard deviation) of −10.8 ± 16.6% (95% confidence interval, −13.46 to −7.52) and for placebo, −4.0 ± 15.7% (95% confidence interval, −7.73–0.31; p = 0.007 using two-way analysis of variance). This effect corresponded to changes from baseline in total daily awake “off” time of −1.8 ± 2.8 hours for istradefylline and −0.6 ± 2.7 hours for placebo (p = 0.005). Treatment-emergent adverse effects with istradefylline were generally mild.
Istradefylline was safe, well tolerated, and offered a clinically meaningful reduction in “off” time without increased troublesome dyskinesia. Ann Neurol 2008