ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson's Disease (EASE LID 2 Study): Interim Results of an Open-Label Safety Study

Robert A Hauser; Rajesh Pahwa; Caroline M Tanner; Wolfgang Oertel; Stuart H Isaacson; Reed Johnson; Larissa Felt; Mary Jean Stempien

doi:10.3233/JPD-171134

ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson's Disease (EASE LID 2 Study): Interim Results of an Open-Label Safety Study

J Parkinsons Dis. 2017;7(3):511-522. doi: 10.3233/JPD-171134.

Authors

Robert A Hauser¹, Rajesh Pahwa², Caroline M Tanner³, Wolfgang Oertel⁴, Stuart H Isaacson⁵, Reed Johnson⁶, Larissa Felt⁶, Mary Jean Stempien⁶

Affiliations

¹ University of South Florida, Tampa, FL, USA.
² University of Kansas Medical Center, Kansas City, KS, USA.
³ University of California San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
⁴ Philipps University, Marburg, Germany.
⁵ Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA.
⁶ Adamas Pharmaceuticals, Inc., Emeryville, CA, USA.

Abstract

Background: Medical treatment of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is an unmet need. ADS-5102 (amantadine) extended-release capsules is being developed for the treatment of LID in patients with PD.

Objective: Evaluate the long-term safety and tolerability of 274 mg ADS-5102 for LID in PD.

Methods: In an ongoing, open-label safety study (NCT02202551), PD patients with LID received 274 mg of ADS-5102 once daily at bedtime. Patients were recruited from previous ADS-5102 trials. In addition, patients were enrolled who were ineligible for previous ADS-5102 trials due to previous implantation of deep-brain stimulation (DBS) devices. The primary outcome measure was safety assessed through adverse events (AEs). Efficacy was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part IV and its subparts.

Results: For this interim analysis, 223 patients received ADS-5102 for a mean duration of 348 (SD 182) days. The most common AEs included falls (25.1%), visual hallucinations (19.3%), peripheral edema (13.0%), and constipation (12.6%). Overall, 32 patients (14.3%) discontinued due to an AE. In patients receiving placebo in previous studies, the mean MDS-UPDRS, Part IV scores decreased by 3.4 points from baseline (n = 78) to week 8 and remained stable through week 64 (n = 21). In patients receiving ADS-5102 in previous studies, the mean baseline (n = 61) MDS-UPDRS, Part IV score was low due to the response to ADS-5102 in previous studies and remained stable through week 64 (total of 88 weeks; n = 21). The effect was primarily due to reduction in item 4.2 (functional impact of dyskinesia) and item 4.4 (functional impact of motor fluctuations).

Conclusions: ADS-5102 was generally well tolerated in all groups, including DBS patients, and the safety profile was consistent with previous controlled studies. Long-term durability and tolerability were shown from the double-blind studies through participation in the open-label study up to 88 weeks.

Keywords: Parkinson’s disease; amantadine; dyskinesia; levodopa-induced dyskinesia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Amantadine / therapeutic use*
Double-Blind Method
Drug Delivery Systems
Dyskinesia, Drug-Induced / drug therapy*
Female
Humans
Kaplan-Meier Estimate
Levodopa / adverse effects*
Male
Middle Aged
Treatment Outcome

Substances

Levodopa
Amantadine

Associated data

ClinicalTrials.gov/NCT02202551
ClinicalTrials.gov/NCT02202551