A 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson disease.
BACKGROUND
The safety and efficacy of istradefylline, a selective adenosine A(2A) receptor antagonist, was evaluated in a 12-week, double-blind study in levodopa-treated Parkinson disease (PD) subjects with motor complications.


METHODS
Levodopa-treated PD subjects (n = 395) received istradefylline 20 mg/day (n = 163), istradefylline 60 mg/day (n = 155), or placebo (n = 77) at 40 sites. The primary efficacy variable was the change in the percentage of time per day spent in the OFF state. Secondary measurements assessed change in ON time, Unified Parkinson's Disease Rating Scale, and Clinical Global Impression. Safety monitoring included clinical laboratory, electrocardiograms, vital signs, physical/neurologic examinations, and adverse events (AEs).


RESULTS
Changes from baseline to endpoint in the percentage OFF time in the active groups compared with placebo were -4.35% (95% CI -8.16 to -0.54; p = 0.026) for istradefylline 20 mg/day and -4.49% (95% CI -8.35 to -0.62; p = 0.024) for 60 mg/day; these changes were significant (analysis of covariance). For total hours, istradefylline demonstrated mean differences from placebo of -0.64 hours (95% CI -1.30 to 0.01) for 20 mg/day and -0.77 hours (95% CI -1.44 to -0.11) for 60 mg/day (p = 0.065; overall treatment effect). Clinical response occurred by the second week and was maintained throughout the study. Istradefylline was well tolerated. The common AEs were dyskinesia, nausea, dizziness, and hallucinations.


CONCLUSIONS
Istradefylline demonstrated a significant reduction in the percentage of awake time per day spent in the OFF state, which resulted in a clinically meaningful reduction in OFF time, without an increase in ON time with troublesome dyskinesia, and was well tolerated as adjunctive treatment to levodopa in Parkinson disease.
Division of Neurology, Duke University Medical Center, Durham, NC 27705, USA. mark.stacy@duke.edu
M
M
Stacy
D
D
Silver
T
T
Mendis
J
J
Sutton
A
A
Mori
P
P
Chaikin
N M
NM
Sussman
D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000978:Antiparkinson Agents; D018492:Dopamine Antagonists; D011687:Purines; C111599:istradefylline