Abstract Details

Title A phase 2, placebo-controlled, randomized, double-blind trial of tozadenant (SYN-115) in patients with Parkinson’s disease with wearing-off fluctuations on levodopa

Topic Movement Disorders

Presentation(s) (-)

Poster/Presentation
Number 005

Objective

Background Tozadenant is an oral, selective adenosine 2-alpha receptor antagonist.

Design/Methods This was an international, 12-week, double-blind, phase 2 trial in which patients on stable dosages of levodopa with at least 2.5 hr of OFF time/day were randomized to tozadenant 60, 120, 180 or 240 mg BID, or matching placebo. Primary outcome measure was change from baseline to Week 12 in hr/day spent in the OFF state. A mixed-model repeated-measures ANCOVA was used for analyses with a prespecified hierarchical step-down approach to test multiple dose groups.

Results Of 420 patients randomized, 337 completed treatment: mean age, 63.3 yr; PD duration, 8.7 yr; baseline OFF time, ∼6 hr. Significant reductions in mean placebo-corrected change from baseline in OFF time were observed with tozadenant (mITT population) 120 mg BID (-1.1 hr, p=0.0039) and 180 mg BID (-1.2 hr, p=0.0039). ON time with troublesome dyskinesia was not significantly increased in any tozadenant group. Mean placebo-corrected UPDRS III scores significantly improved with tozadenant 120 mg BID (-2.2, p=0.0325) and 180 mg BID (-2.5, p=0.0325). Mean placebo-corrected UPDRS I-III scores improved significantly in all tozadenant groups (all groups, p≤ 0.03) as did mean placebo-corrected CGI-I and CGI-S scores. PGI-I scores significantly improved in the 120 mg BID group. Most common AEs in the combined tozadenant groups were dyskinesia, nausea, dizziness, constipation, PD worsening, insomnia, and falls.

Conclusions Tozadenant, at a daily dosage of 120 or 180 mg BID, was generally well tolerated and demonstrated efficacy in reducing OFF time and improving motor signs without significantly increasing troublesome dyskinesia. These two dosages can be considered for future trials.

Authors/Disclosures
C. W. Olanow, MD	Dr. Olanow has received personal compensation for serving as an employee of Clintrex Research Corporation. Dr. Olanow has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Clintrex Research Corporation. Dr. Olanow has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Chevron/Syngenta. Dr. Olanow has stock in Clintrex Research Corporation.
Robert A. Hauser, MD, MBA, FAAN (Movement Disorders Center)	Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Global Kinetics Consulting (GKC). Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa Kirin Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroDerm. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Scion Neurostim LLC. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sunovion Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tolmar Inc.. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Revance Therapeutics. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Supernus Pharma. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merz. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Pharma 2 B. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vivifi Biotech. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ovid Therapeutics. Dr. Hauser has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Amneal. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AgeX Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avanex. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BlueRock Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MDCE Suzhou. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedRhythms. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PDNeurotechnology. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Regenxbio. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Tremor Research Support Group. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tris Pharma. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Hauser has received personal compensation in the range of $0-$499 for serving as a Consultant for Canfield Scientific. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Forsee Pharmaceuticals. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KiefeRx. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Intrance. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zambon. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Truebinding. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Serina Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nano PharmaSolutions. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for HanAll. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inhibikase. The institution of Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoparkinson. The institution of Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Photopharmics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Acorda Therapeutics. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Amneal . Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Neurocrine. Dr. Hauser has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Cerevel. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Inhibikase. Dr. Hauser has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Supernus. Dr. Hauser has stock in Inhibikase. Dr. Hauser has stock in Axial Therapeutics. Dr. Hauser has stock in Enterin. Dr. Hauser has stock in Revance Therapeutics. The institution of Dr. Hauser has received research support from Annovis Bio, Inc.. The institution of Dr. Hauser has received research support from Inhibikase Therapeutics. The institution of Dr. Hauser has received research support from AbbVie, Inc.. The institution of Dr. Hauser has received research support from Aeon Biopharma. The institution of Dr. Hauser has received research support from Biogen MA. The institution of Dr. Hauser has received research support from Bukwang Pharmaceutical Co., Ltd.. The institution of Dr. Hauser has received research support from Cavion, Inc.. The institution of Dr. Hauser has received research support from Cerevance Beta, Inc.. The institution of Dr. Hauser has received research support from Cerevel Therapeutics. The institution of Dr. Hauser has received research support from Enterin, Inc.. The institution of Dr. Hauser has received research support from Genentech. The institution of Dr. Hauser has received research support from Global Kinetics Corporation. The institution of Dr. Hauser has received research support from Hoffman-La Roche Inc. The institution of Dr. Hauser has received research support from Michael J. Fox Foundation for Parkinson's Research. The institution of Dr. Hauser has received research support from National Parkinson's Foundation. The institution of Dr. Hauser has received research support from Neuraly Inc.. The institution of Dr. Hauser has received research support from Neuroderm. The institution of Dr. Hauser has received research support from Sage Therapeutics. The institution of Dr. Hauser has received research support from Sanofi Pharmaceuticals. The institution of Dr. Hauser has received research support from Scion NeuroStim. The institution of Dr. Hauser has received research support from UCB BioPharma. The institution of Dr. Hauser has received research support from UCB. The institution of Dr. Hauser has received research support from MJFF. The institution of Dr. Hauser has received research support from Biogen. The institution of Dr. Hauser has received research support from Alexza Pharmaceuticals. Dr. Hauser has received intellectual property interests from a discovery or technology relating to health care.
Karl D. Kieburtz, MD (University of Rochester Medical Center)	Dr. Kieburtz has received personal compensation for serving as an employee of Clintrex Research Corporation. Dr. Kieburtz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Kieburtz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Kieburtz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Kieburtz has stock in Clintrex Research Corp. Dr. Kieburtz has stock in Hoover Brown. An immediate family member of Dr. Kieburtz has stock in Hoover Brown. Dr. Kieburtz has stock in Safe Therapeutics. The institution of Dr. Kieburtz has received research support from NIH. The institution of Dr. Kieburtz has received research support from Michae J Fox Foundation.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Michael S. Okun, MD, FAAN (University of Florida)	Dr. Okun has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NIH. Dr. Okun has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Parkinson's Foundation. Dr. Okun has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Okun has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NEJM Journal Watch. The institution of Dr. Okun has received research support from NIH. The institution of Dr. Okun has received research support from Parkinson's Foundation. The institution of Dr. Okun has received research support from Tourette Association of America. The institution of Dr. Okun has received research support from Michael J Fox. Dr. Okun has received publishing royalties from a publication relating to health care.
	No disclosure on file

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