Abstract Details

Title Amantadine DR/ER Improved OFF-State Dystonia Motor Complications in PD

Topic Movement Disorders

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 5-004

Background

Dystonia is a painful OFF-state related motor complication in PD. AMT DR/ER is the only medication approved to treat dyskinesia and OFF in levodopa-treated patients. We evaluated whether AMT DR/ER reduces dystonia in patients with PD with motor complications.

Objective

To evaluate the effect of amantadine delayed release/extended release’s (AMT DR/ER) on OFF-state dystonia related motor complications in patients with Parkinson’s disease (PD).

Design/Methods

AMT DR/ER efficacy was evaluated using post-hoc evaluation of pooled AMT DR/ER pivotal trials in patients with motor complications (dyskinesia with/without OFF). Dystonia was assessed using UDysRS Part 2A and 2B during the blinded phase and MDS-UPDRS Part IV, item 4.6 (during the blinded phase and open-label [OL] follow-on study). During the pivotal trials, participants were randomized to AMT DR/ER (titrated to 274 mg/day) or placebo; participants could continue and receive OL AMT DR/ER for up to 2 years (100 weeks).

Results

Of 196 participants evaluated, 61% (n=119) experienced OFF dystonia on UDysRS Part 2A at baseline and 35% (n=69) reported >30 minutes/day of dystonia. At Week 12 vs baseline, AMT DR/ER significantly improved dystonia on UDysRS Part 2 (P=0.027) and MDS-UPDRS Part IV item 4.6 (P=0.021); improvements were seen in duration and severity of dystonia (UDysRS Part 2A and 2B, respectively). More participants receiving AMT DR/ER showed improved UDysRS Part 2A (39% vs 26% placebo) and 2B (43.9% vs 40.2% placebo), whereas more receiving placebo showed worsening on Part 2A (25% vs 8.5% on AMT DR/ER) and 2B (26% vs 17%, respectively). MDS-UPDRS Part IV item 4.6 improvements sustained below double-blind baseline through OL extension up to Week 100.

Conclusions

Current analyses showed AMT DR/ER reduced OFF dystonia under double-blind testing and reductions appeared sustained to Week 100 in the OL study. Reductions in dystonia derived from reduction in scores for time and severity, with the former reaching significance.

Authors/Disclosures
Caroline M. Tanner, MD, PhD, FAAN (University of California San Francisco, Weill Institute for Neurosciences) PRESENTER	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.
Jill L. Ostrem, MD, FAAN (UCSF)	Dr. Ostrem has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Dr. Ostrem has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Ostrem has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz . Dr. Ostrem has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Superness. Dr. Ostrem has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AcureX. Dr. Ostrem has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorders. The institution of Dr. Ostrem has received research support from Neuroderm. The institution of Dr. Ostrem has received research support from Boston Scientific. The institution of Dr. Ostrem has received research support from Medtronic. The institution of Dr. Ostrem has received research support from Rune.
Judy Lytle	Judy Lytle has received personal compensation for serving as an employee of Adamas Pharmaceuticals, Inc. Judy Lytle has received stock or an ownership interest from Adamas Pharmaceuticals, Inc.
Andrea Formella, PharmD, BCPP (Supernus Pharmaceuticals)	Dr. Formella has received personal compensation for serving as an employee of Adamas Pharmaceuticals, Inc. Dr. Formella has received personal compensation for serving as an employee of Supernus Pharmaceuticals, Inc. Dr. Formella has stock in Adamas Pharmaceuticals. Dr. Formella has stock in Supernus Pharmaceuticals, Inc..
Alberto J. Espay, MD, FAAN (University of Cincinnati)	Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuroderm. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amneal. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acorda. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa Kirin. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sunovion. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Herantis Pharma. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Supernus (formerly USWorldMeds). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Synaps Dx. Dr. Espay has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AskBio. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Supernus (formerly, USWorldMeds). Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal. Dr. Espay has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Avion Pharmaceuticals. The institution of Dr. Espay has received research support from NIH. The institution of Dr. Espay has received research support from Michael J Fox Foundation for Parkinson's Research. Dr. Espay has received intellectual property interests from a discovery or technology relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care. Dr. Espay has received publishing royalties from a publication relating to health care.