Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD.

Abstract

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: Robert A Hauser, Jean P Hubble, Daniel D Truong, Istradefylline US-001 Study Group
• Journal: Neurology (Neurology) Vol. 61 Issue 3 Pg. 297-303 (Aug 12 2003) ISSN: 1526-632X [Electronic] United States
• PMID: 12913187 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A2 Receptor Antagonists
• Antiparkinson Agents
• Catechol O-Methyltransferase Inhibitors
• Dopamine Agonists
• Enzyme Inhibitors
• Purines
• istradefylline
• Selegiline
• Levodopa

Topics

• Adenosine A2 Receptor Antagonists
• Aged
• Antiparkinson Agents (adverse effects, therapeutic use)
• Catechol O-Methyltransferase Inhibitors
• Chronic Disease
• Dopamine Agonists (administration & dosage)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Dyskinesia, Drug-Induced (etiology)
• Enzyme Inhibitors (administration & dosage)
• Female
• Humans
• Levodopa (administration & dosage)
• Male
• Nausea (chemically induced)
• Parkinson Disease (drug therapy)
• Purines (adverse effects, therapeutic use)
• Safety
• Selegiline (administration & dosage)
• Treatment Outcome