Abstract Details

Title ADS-5102 (amantadine HCl) Extended-Release Capsules Reduced Levodopa-Induced Dyskinesia in the Phase 3 EASE LID Study

Topic Movement Disorders

Presentation(s) (-)

Poster/Presentation
Number 014

Background ADS-5102 is designed to improve the pharmacokinetic profile of immediate-release amantadine, with the aim of enhancing efficacy without compromising tolerability.

Objective

Design/Methods We conducted a double-blind, placebo-controlled study (NCT02136914) in which 126 Parkinson’s disease (PD) subjects with LID were randomized (1:1) to placebo or ADS-5102. The primary outcome measure was the change from baseline to Week 12 in the Unified Dyskinesia Rating Scale (UDysRS) total score. Secondary measures included the change from baseline to Week 24 in the UDysRS total score; the change from baseline to Weeks 12 and 24 in daily PD states as measured by subject diaries and the Clinician’s Global Impression of Change (CGI-C) of overall PD symptoms, including LID.

Results ADS-5102 significantly reduced the UDysRS total score vs placebo at Week 12 (p=0.0009) and Week 24 (p=0.0008). Daily ON time without troublesome dyskinesia increased significantly vs placebo (2.7 hrs at Week 12, p<0.0001; 2.2 hrs at Week 24, p=0.0007). Daily OFF time decreased significantly vs placebo (-0.9 hrs at Week 12, p=0.0171; -0.8 hrs at Week 24, p=0.0406). At Week 12, 60% of ADS-5102 vs 19% of placebo subjects were rated moderately to markedly improved based on the CGI-C. The most frequent adverse events (AE) were hallucinations, peripheral edema, dizziness, dry mouth, constipation, and falls. Treatment discontinuations due to AEs occurred in 21% of ADS-5102 subjects vs 7% of placebo subjects.

Conclusions ADS-5102 was generally well tolerated and resulted in improvement in LID which was sustained over 24 weeks. A reduction in daily OFF time was also demonstrated.

Authors/Disclosures
Rajesh Pahwa, MD, FAAN (University of Kansas Medical Center)	Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AbbVie. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ACADIA. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amneal. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Insightec. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jaaz. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fasikl. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genetech. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merz. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Photopharmics. The institution of Dr. Pahwa has received research support from Abbott. The institution of Dr. Pahwa has received research support from Abbvie. The institution of Dr. Pahwa has received research support from Biogen. The institution of Dr. Pahwa has received research support from Parkinson Foundation. The institution of Dr. Pahwa has received research support from Roche. The institution of Dr. Pahwa has received research support from Sage. The institution of Dr. Pahwa has received research support from Sun Pharma. The institution of Dr. Pahwa has received research support from Theravance. The institution of Dr. Pahwa has received research support from Neuroderm. The institution of Dr. Pahwa has received research support from Ask Bio. The institution of Dr. Pahwa has received research support from Blue Rock. The institution of Dr. Pahwa has received research support from Cerevance. The institution of Dr. Pahwa has received research support from Fasikl. The institution of Dr. Pahwa has received research support from Scion. The institution of Dr. Pahwa has received research support from UCB. The institution of Dr. Pahwa has received research support from Ono. The institution of Dr. Pahwa has received research support from Intra-cellular Therapies. The institution of Dr. Pahwa has received research support from Ask Bio. The institution of Dr. Pahwa has received research support from Michael J Fox Foundation . The institution of Dr. Pahwa has received research support from Neuron 23. The institution of Dr. Pahwa has received research support from Roche.
Caroline M. Tanner, MD, PhD, FAAN (University of California San Francisco, Weill Institute for Neurosciences)	Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Evidera. Dr. Tanner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine. Dr. Tanner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz Pharmaceuticals/Cavion. Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial . Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Supernus. Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Genentech. The institution of Dr. Tanner has received research support from Gateway LLC. The institution of Dr. Tanner has received research support from Roche\Genentech. The institution of Dr. Tanner has received research support from Michael J Fox Foundation . The institution of Dr. Tanner has received research support from National Institute of Health . The institution of Dr. Tanner has received research support from Department of Defense. Dr. Tanner has received personal compensation in the range of $500-$4,999 for serving as a Faculty, CME presentation with Medscape /WebND.
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.
Paul A. Nausieda, MD, FAAN (Wisconsin Institute for Neuro & Sleep)	No disclosure on file
Daniel D. Truong, MD, FAAN (PMDI)	The institution of Dr. Truong has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Truong has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal. The institution of Dr. Truong has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Neurocrine Biosciences. The institution of Dr. Truong has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Truong has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Truong has received research support from Abbvie. The institution of Dr. Truong has received research support from Aeon. The institution of Dr. Truong has received research support from Biogen. The institution of Dr. Truong has received research support from Bukwang. The institution of Dr. Truong has received research support from Cerevel. The institution of Dr. Truong has received research support from Eli Lilly. The institution of Dr. Truong has received research support from Enterin. The institution of Dr. Truong has received research support from Ipsen. The institution of Dr. Truong has received research support from Lundbeck. The institution of Dr. Truong has received research support from Neurocrine. The institution of Dr. Truong has received research support from Neuroderm. The institution of Dr. Truong has received research support from Parkinson Foundation. The institution of Dr. Truong has received research support from Prilenia. The institution of Dr. Truong has received research support from Revance. The institution of Dr. Truong has received research support from Sunovion. Dr. Truong has received publishing royalties from a publication relating to health care. Dr. Truong has received publishing royalties from a publication relating to health care. Dr. Truong has a non-compensated relationship as a President with International Association for Parkinsonism and Related Disorders that is relevant to AAN interests or activities.
Keith L. Hull, Jr., MD, FAAN	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Natalie L. McClure, PhD (Adamas Pharmaceuticals, Inc.)	No disclosure on file
Mary Jean Stempien, MD (ADAMAS Pharmaceuticals)	No disclosure on file

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