PMID- 18519872
OWN - NLM
STAT- MEDLINE
DCOM- 20080616
LR  - 20220321
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 70
IP  - 23
DP  - 2008 Jun 3
TI  - A 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson 
      disease.
PG  - 2233-40
LID - 10.1212/01.wnl.0000313834.22171.17 [doi]
AB  - 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.
FAU - Stacy, M
AU  - Stacy M
AD  - Division of Neurology, Duke University Medical Center, Durham, NC 27705, USA. 
      mark.stacy@duke.edu
FAU - Silver, D
AU  - Silver D
FAU - Mendis, T
AU  - Mendis T
FAU - Sutton, J
AU  - Sutton J
FAU - Mori, A
AU  - Mori A
FAU - Chaikin, P
AU  - Chaikin P
FAU - Sussman, N M
AU  - Sussman NM
LA  - eng
SI  - ClinicalTrials.gov/NCT00456794
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Purines)
RN  - 2GZ0LIK7T4 (istradefylline)
SB  - IM
EIN - Neurology. 2008 Sep16;71(12): 953
MH  - Aged
MH  - Antiparkinson Agents/administration & dosage/adverse effects/therapeutic use
MH  - Dopamine Antagonists/administration & dosage/adverse effects/therapeutic use
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Parkinson Disease/*drug therapy
MH  - Purines/administration & dosage/adverse effects/*therapeutic use
EDAT- 2008/06/04 09:00
MHDA- 2008/06/17 09:00
CRDT- 2008/06/04 09:00
PHST- 2008/06/04 09:00 [pubmed]
PHST- 2008/06/17 09:00 [medline]
PHST- 2008/06/04 09:00 [entrez]
AID - 70/23/2233 [pii]
AID - 10.1212/01.wnl.0000313834.22171.17 [doi]
PST - ppublish
SO  - Neurology. 2008 Jun 3;70(23):2233-40. doi: 10.1212/01.wnl.0000313834.22171.17.