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.

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.

• Authors: Robert A Hauser, Rajesh Pahwa, Caroline M Tanner, Wolfgang Oertel, Stuart H Isaacson, Reed Johnson, Larissa Felt, Mary Jean Stempien
• Journal: Journal of Parkinson's disease (J Parkinsons Dis) Vol. 7 Issue 3 Pg. 511-522 ( 2017) ISSN: 1877-718X [Electronic] Netherlands
• PMID: 28777755 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Levodopa
• Amantadine

Topics

• 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