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

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.

Figures

Fig.1
Fig.1
Trial Profile. aStudy includes 22 patients who enrolled after a time gap following participation in double-blind studies (EASED, EASE LID, EASE LID 3) and were not summarized as a subgroup in subsequent analyses due to small sample size. bCase report form in interim data-cut for 2 additional patients reported study drug withdrawal as action taken in response to AE, while disposition record reported “other” and “ongoing.”
Fig.2
Fig.2
Kaplan-Meier curves for Discontinuation Due to Adverse Event.
Fig.3
Fig.3
MDS-UPDRS Part IV – Double-blind/Open-Label Study Experience. MDS-UPDRS, Movement Disorder Society–Unified Parkinson’s Disease Rating Scale.
Fig.4
Fig.4
MDS-UPDRS Part IV Scores. MDS-UPDRS, Movement Disorder Society–Unified Parkinson’s Disease Rating Scale.

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