Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study).

Abstract

ADS-5102 is a long-acting, extended-release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS-5102 in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled, parallel-group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS-5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS-5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ-39). ADS-5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P = 0.005). In addition, ADS-5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P = 0.004), 340 mg (P = 0.008) and 420 mg (P = 0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260-mg, 340-mg, and 420-mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS-5102 was generally well tolerated and resulted in significant and dose-dependent improvements in dyskinesia in PD patients.

• Authors: Rajesh Pahwa, Caroline M Tanner, Robert A Hauser, Kapil Sethi, Stuart Isaacson, Daniel Truong, Lynn Struck, April E Ruby, Natalie L McClure, Gregory T Went, Mary Jean Stempien
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 30 Issue 6 Pg. 788-95 (May 2015) ISSN: 1531-8257 [Electronic] United States
• PMID: 25650051 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Adamas Pharmaceuticals, Inc. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Chemical References

• Antiparkinson Agents
• Delayed-Action Preparations
• Levodopa
• Amantadine

Topics

• Adult
• Aged
• Aged, 80 and over
• Amantadine (administration & dosage, therapeutic use)
• Antiparkinson Agents (administration & dosage, adverse effects, therapeutic use)
• Delayed-Action Preparations (administration & dosage, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Dyskinesia, Drug-Induced (drug therapy, physiopathology)
• Female
• Humans
• Levodopa (adverse effects, therapeutic use)
• Male
• Middle Aged
• Parkinson Disease (drug therapy, physiopathology)
• Treatment Outcome