Objective: To observe whether increasing the istradefylline dose from 20 to 40mg/day provides more patients with meaningful clinical responses.

Background: Istradefylline, a well-tolerated selective adenosine A_2A receptor antagonist, acts in the indirect basal ganglia outflow pathway. Doses of 20 and 40mg/day were approved in Japan in 2013 as adjunctive treatment to LD-containing products in PD patients experiencing motor fluctuations. Istradefylline significantly improved OFF-time in placebo-controlled, fixed-dose studies, with similar mean efficacy responses for 20 and 40mg/day doses.

Method: Istradefylline was evaluated in PD patients receiving LD and experiencing motor fluctuations. In this open-label extension study, extended from a Phase 3, randomized, placebo-controlled, double-blind trial of istradefylline, patients (N=308) received a starting once-daily oral dose of istradefylline 20mg/day. The dose could be increased to 40mg once daily after 4 weeks if there was good tolerability, suboptimal treatment response, and patient agreement. At Week 8, change in daily OFF-time and ON-time (using patient-completed 24-hour ON/OFF diaries) and Clinical Global Impression-Global Improvement (CGI-I) were assessed and compared with Week 4. Adverse events (AEs) were recorded throughout.

Results: Baseline characteristics were similar between analysis groups (remained on 20mg or increased to 40mg). At Week 8, the percentage of patients with ≥1-hr reduction in daily OFF-time was greater among those whose istradefylline dose was increased to 40mg vs those who remained on 20mg (Table). Similarly, a greater percentage of patients had ≥1-hr increase in ON-time without troublesome dyskinesia and improved CGI-I scores when istradefylline dose was increased to 40mg compared with those who remained on 20mg (Table). In randomized, placebo-controlled, double-blind trials of istradefylline, dyskinesia was the most frequently reported AE, with similar incidence in 20 and 40mg/day treatment groups. [table1]

Conclusion: These results demonstrate that for patients whose response to istradefylline 20mg/day was suboptimal, increasing the dose to 40mg/day resulted in a greater percentage of patients with improvements in patient-reported OFF-time, ON-time without troublesome dyskinesia, and physician-rated CGI-I scores. Sponsor of studies: Kyowa Hakko Kirin Co., Ltd.

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-an-increase-in-dose-of-istradefylline-an-a2a-receptor-antagonist-in-levodopa-ld-treated-patients-with-parkinsons-disease-pd/