Abstract Details

Title Effect of an Increase in Dose of Istradefylline, an A2A Receptor Antagonist, in Levodopa-Treated Patients with Parkinson’s Disease

Topic Movement Disorders

Presentation(s) P9 - Poster Session 9 (12:00 PM-1:00 PM)

Poster/Presentation
Number 3-016

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

Background Istradefylline is an adenosine A_2Areceptor antagonist indicated as adjunctive treatment to levodopa (LD)/carbidopa in adult patients with Parkinson’s disease (PD) experiencing OFF episodes. Istradefylline significantly reduced OFF time in placebo-controlled, fixed-dose studies, with similar efficacy responses for 20 and 40mg/day doses.

Design/Methods Istradefylline was evaluated in PD patients receiving LD and experiencing motor fluctuations. In this open-label extension study (NCT00957203), following a Phase 3, randomized, placebo-controlled trial of istradefylline, patients (N=308) received a once-daily oral dose of istradefylline 20mg/day. The dose could be increased to 40mg once-daily after 4 weeks if there were no safety concerns, unsatisfactory treatment response, and patient agreement. At Week 8, change in daily OFF 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. Treatment-emergent adverse events (TEAEs) were recorded throughout.

Results Baseline characteristics were similar between analysis groups (remained on 20mg/day, increased to 40mg/day). At Week 8, 30.0% of patients whose istradefylline dose was increased to 40mg/day had ≥1-hr reduction in daily OFF time, vs 13.8% of patients remaining on 20mg. Similarly, 34.4% and 25.6% of patients whose dose increased to 40mg/day had ≥1-hr increase in ON time without troublesome dyskinesia and improved CGI-I scores, respectively, compared with 14.6% and 14.4%, respectively, for those remaining on 20mg/day. Among TEAEs with frequency ≥5%, those that became more frequent with dose increase to 40mg/day vs maintained at 20mg/day were nasopharyngitis, dyskinesia, contusion, and constipation.

Conclusions These results demonstrate that for patients whose response to istradefylline 20mg/day was considered 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.

Authors/Disclosures
Nobutaka Hattori, MD, PhD, FANA (Juntendo University School of Medicine) PRESENTER	Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PARKINSON Laboratories Co., Ltd. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyowa Kirin Co., Ltd. . Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TEIJIN PHARMA LIMITED.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sumitomo Dainippon Pharma Co., Ltd.. Prof. Hattori has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Pharmaceutical Co., Ltd.. Prof. Hattori has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Kyowa Kirin Co., Ltd. . Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie GK. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai Co., Ltd. . Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otsuka Holdings Co.,Ltd.. Prof. Hattori has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Ono Pharmaceutical Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai Co., Ltd. . Prof. Hattori has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sumitomo Dainippon Pharma Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharma Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis Pharma K.K.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for DAIICHI SANKYO Co., Ltd.. Prof. Hattori has received stock or an ownership interest from PARKINSON Laboratories Co., Ltd. The institution of Prof. Hattori has received research support from Japan Society for the Promotion of Science (JSPS). The institution of Prof. Hattori has received research support from Japan Agency for Medical Research and Development (AMED). The institution of Prof. Hattori has received research support from Japan Science and Technology Agency, Health Labour Sciences Research Grant. The institution of Prof. Hattori has received research support from Japan Science and Technology Agency (JST). The institution of Prof. Hattori has received research support from Kyowa Kirin Co.,Ltd.. The institution of Prof. Hattori has received research support from Medtronic, Inc.. The institution of Prof. Hattori has received research support from Boston Scientific Corporation. The institution of Prof. Hattori has received research support from TEIJIN PHARMA LIMITED.. The institution of Prof. Hattori has received research support from AbbVie GK. The institution of Prof. Hattori has received research support from FP Pharmaceutical Corporation. The institution of Prof. Hattori has received research support from Dai-Nippon Sumitomo Pharma Co.,Ltd. The institution of Prof. Hattori has received research support from Nihon Medi-physics Co.,Ltd.,. The institution of Prof. Hattori has received research support from Eisai Co.,Ltd. . The institution of Prof. Hattori has received research support from Kirin Holdings Company, Limited. The institution of Prof. Hattori has received research support from Mitsubishi UFJ Trust and Banking Corporation. The institution of Prof. Hattori has received research support from GLORY LTD.. The institution of Prof. Hattori has received research support from Nippon Life Insurance Company. The institution of Prof. Hattori has received research support from Otsuka Pharmaceutical, Co.,Ltd. The institution of Prof. Hattori has received research support from AbbVie GK,. The institution of Prof. Hattori has received research support from Meiji Seika Pharma Co., Ltd.. The institution of Prof. Hattori has received research support from Ono Pharmaceutical Co., Ltd.. The institution of Prof. Hattori has received research support from FUJIFILM Wako Pure Chemical Corporation. The institution of Prof. Hattori has received research support from Sunwels,Inc.. The institution of Prof. Hattori has received research support from OHARA Pharmaceutical Co.,Ltd.. The institution of Prof. Hattori has received research support from PARKINSON Laboratories Co., Ltd.. The institution of Prof. Hattori has received research support from Ono Pharmaceutical Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving as a Team Leader with RIKEN Center for Brain Science. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving as a Program officer with AMED: Japan Agency for Medical Research and Development.
	No disclosure on file
Phyllis M. Salzman, PhD	No disclosure on file
	No disclosure on file
	No disclosure on file
Keizo Toyama	No disclosure on file
Akihisa Mori, PhD (SNLD, Ltd.)	Mr. Mori has received personal compensation for serving as an employee of SNLD, Ltd., Japan.

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Abstract Details