Safety and Efficacy Study of ADS-5102 (Amantadine HCl) Extended Release Capsules in Levodopa-Induced Dyskinesia (EASED Study) (P4.053)

OBJECTIVE: Investigate the safety and efficacy of 3 doses of once-nightly administration of ADS-5102 (amantadine HCl) extended release capsules for the treatment of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD) BACKGROUND: LID is a dose limiting adverse effect of PD treatment. Pharmacokinetic profile of ADS-5102 may improve tolerability and permit higher doses than immediate release amantadine leading to better LID treatment. DESIGN/METHODS: Randomized, double-blind, placebo-controlled, parallel-group study was conducted at 31 U.S. sites (NCT 01397422). PD patients with troublesome LID were randomized to placebo or one of 3 doses of ADS-5102 (260 mg, 340 mg, 420 mg), dosed once nightly for 8 weeks. The primary outcome measure was the change from baseline to week 8 in the Unified Dyskinesia Rating Scale (UDysRS) total score. Secondary outcome measures were: change from baseline in 24-hour PD patient diaries, the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Clinician’s Global Impression of Change (CGI-C). RESULTS: 83 subjects were randomized. The study met its primary endpoint; both the 340 mg and 420 mg dose levels significantly reduced LID as measured by change in the UDysRS total score over 8 weeks vs placebo (p=0.005 and p=0.013, respectively). ON time without troublesome dyskinesia, as measured by diaries, increased by approximately 3 hours over 8 weeks vs placebo (260 mg p=0.004, 340 mg p=0.008 and 420 mg p=0.018). ADS-5102 at the 340 mg and 420 mg dose levels reduced motor complications of PD as measured by change from baseline to week 8 in MDS-UPDRS, Part IV (p=0.03, p=0.003, respectively). 75% of subjects assigned to the 340 mg dose level had a moderate to marked improvement in the CGI-C at week 8, versus 32% of placebo subjects. The most frequent AEs were constipation, dizziness, dry mouth and hallucinations. CONCLUSION: ADS-5102 in once nightly doses up to 420 mg was generally well tolerated and resulted in significant and dose-dependent improvements in LID. Study Supported by: Adamas Pharmaceuticals Disclosure: Dr. Pahwa has received personal compensation for activities with Teva Neuroscience, Merck Serono, Novartis, Medtronic Inc., GE Healthcare, Impax Laboratories, Ceregene, Noven, Adamas, and St. Jude Medical as a consultant. Dr. Pahwa has received personal compensation in an editorial capacity for the International Journal of Neuroscience. Dr. Tanner has received personal compensation for activities with AbbVie and Adamas Pharmaceuticals as a scientific advisor. Dr. Hauser has received personal compensation for activities with Abbott Laboratories, Allergan, Inc., AstraZeneca, Biotie Therapeutics Inc., Ceregene, Inc., Chelsea Therapeutics, Inc., GE Healthcare, Impax Laboratories, Inc., Ipsen Biopharmaceuticals, Inc., Lundbeck, Merck/MSD, Noven Pharmaceuticals, Inc., Strakan Pharmaceuticals. Dr. Hauser has received royalty, or license fee, or contractual rights payments from University of South Florida. Dr. Hauser has received research support from Abbott Laboratories, Addex Therapeutics, Allergan, Inc., AstraZeneca, Biotie Therapeutics Inc., Chelsea Therapeutics, Inc., GE Healthcare, and Impax Laboratories. Dr. Sethi has received personal compensation for activities with Synosia and Veloxis, ADAMAS, Impax Laboratories and Teva Neuroscience as a consultant, and with Merz Pharmaceuticals as an employee. Dr. Sethi has received research support from GlaxoSmithKline Inc., Teva Neuroscience, Acadia, and Impax Laboratories. Dr. Isaacson has received personal compensation for activities with Acadia, Allergan Inc., Brittania, Chelsea, General Electric, GlaxoSmithKline Inc., Impax Laboratories, Ipsen, Lundbeck, Medtronic Inc., Merz Pharma, Novartis, Teva Neuroscience, UCB Pharma, US World Meds. Dr. Isaacson has received research support from AbbVie, Acadia, ADAMAS, Addex, Allergan Inc., Allon, AstraZeneca, Biotie, Chelsea, Civitas, Eisai Inc., GlaxoSmithKline Inc., Ipsen, Kyowa, Eli Lilly & Co., Merck Schering, Merz Pharma, Michael J Fox Foundation, Novartis, Neurocrine, National Institutes of Health, Novartis, and Orion. Dr. Truong has received personal compensation for activities with Ipsen, Allergan Inc., Schering-Plough Corp., and Novartis as a consultant. Dr. Struck has nothing to disclose. Dr. Stempien has nothing to disclose. Dr. McClure has nothing to disclose. Dr. Went has received personal compensation for activities with Adamas Pharmaceuticals as an employee. Dr. Went holds stock and/or stock options in Adamas Pharmaceuticals which sponsored research in which Dr. Went was involved as an investigator.