title: 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: University of Kansas Medical Center, Kansas City, Kansas, USA.
authors: Rajesh
authors: R
authors: Pahwa
authors: The Parkinson's Institute, Sunnyvale, CA, San Francisco Veterans Affairs Medical Center and University of California-San Francisco, San Francisco, California, USA.
authors: Caroline M
authors: CM
authors: Tanner
authors: University of South Florida, Tampa, Florida, USA.
authors: Robert A
authors: RA
authors: Hauser
authors: Georgia Regents University, Augusta, Georgia, USA.
authors: Kapil
authors: K
authors: Sethi
authors: Parkinson's Disease and Movement Disorders Center, Boca Raton, Florida, USA.
authors: Stuart
authors: S
authors: Isaacson
authors: Parkinson's & Movement Disorder Institute, Fountain Valley, California, USA.
authors: Daniel
authors: D
authors: Truong
authors: Iowa Health Physicians, Des Moines, Iowa, USA.
authors: Lynn
authors: L
authors: Struck
authors: Adamas Pharmaceuticals, Inc., Emeryville, California, USA.
authors: April E
authors: AE
authors: Ruby
authors: Adamas Pharmaceuticals, Inc., Emeryville, California, USA.
authors: Natalie L
authors: NL
authors: McClure
authors: Adamas Pharmaceuticals, Inc., Emeryville, California, USA.
authors: Gregory T
authors: GT
authors: Went
authors: Adamas Pharmaceuticals, Inc., Emeryville, California, USA.
authors: Mary Jean
authors: MJ
authors: Stempien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000547:Amantadine / Q000008:administration & dosage* / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D007980:Levodopa; D000547:Amantadine
keywords: Parkinson's disease; amantadine; clinical trial; levodopa-induced dyskinesia; randomized controlled trial
references: Neurology. 1998 May;50(5):1323-6
references: 9595981
references: J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4
references: 1564476
references: Arch Neurol. 2010 Aug;67(8):996-1001
references: 20697051
references: Trans Am Neurol Assoc. 1971;96:307-8
references: 4945919
references: Antimicrob Agents Chemother. 1981 Feb;19(2):226-33
references: 7347558
references: JAMA. 1969 May 19;208(7):1168-70
references: 5818715
references: Mov Disord. 2012 Jun;27(7):858-63
references: 22674352
references: Mov Disord. 2010 Jul 30;25(10):1357-63
references: 20198649
references: Arch Neurol. 1999 Nov;56(11):1383-6
references: 10555659
references: Mov Disord. 2008 Nov 15;23(15):2129-70
references: 19025984
references: Mov Disord. 2013 Mar;28(3):341-6
references: 23390076
references: J Neurol Sci. 2012 Aug 15;319(1-2):24-31
references: 22664154
references: Mov Disord. 2004 Dec;19(12):1409-13
references: 15390057
references: Mov Disord. 2012 Sep 1;27(10):1239-42
references: 22886777
references: Mov Disord. 2001 May;16(3):448-58
references: 11391738