Study: Amantadine a Dual Threat Against Dyskinesia and Motor Symptoms

JUNE 14, 2017
Kevin Kunzmann
Researchers have found what they believe to be the first documented trial of an oral treatment reducing both levodopa-induced dyskinesia (LID) and the amount of time Parkinson’s disease (PD) medication fails to control motor symptoms in PD patients.
 
A clinical trial sought out the efficacy and safety of 274-mg ADS-5102 (amantadine) — a drug approved by the US Food and Drug Administration for antiviral and antiparkinsonian use — for treating LID from PD. Led by Rajesh Pahwa (pictured), MD, researchers conducted a randomized, double-blind, placebo-controlled trial from May 7, 2014 to July 22, 2015 at 44 North American sites.
 
The trial required patients with PD treated with levodopa who experienced at least 1 hour of “troublesome dyskinesia” per day, with at least mild functional impact, according to the study. Researchers reasoned the trial’s necessity on the basis that medical treatment of LID is currently an unmet need for PD patients.
 
A total of 189 patients were screened, and 126 were randomized to receive either placebo or 274 mg of amantadine orally at bedtime for up to 25 weeks. Primary efficacy was measured on the change in the Unified Dyskinesia Rating Scale (UDRS) total score between the two treatments from baseline to week 12 in the modified intent-to-treat population.
 
The average age of intent-to-treat patients was 64.7 years old. In an editorial review of the study, Aparna Wagle Shukla, MD, noted LID is observed in more than half of PD patients to have received levodopa treatment for 4-6 years, and in more than 90% of patients to have been treated for at least 10 years.
 
“Besides the duration of levodopa therapy, the duration of the disease, the severity of the disease, and the age at onset are other important risk factors,” Shukla wrote. “Levodopa-induced dyskinesia is more frequent, more severe, and presents sooner in patients with PD who present with symptoms before 50 years of age.”
 
The key secondary endpoint of the trial was the measure of medication efficacy against lapse of time in which treatment is not controlling motor symptoms in the PD patients — better called “off time” by the researchers. Safety analyses was included for all patients to receive either treatment.
 
At week 12, PD patients treated with amantadine reported an average UDRS score decrease of 15.9 from baseline. This nearly doubled the reported 8-point decrease in UDRS average score in placebo patients.
 
The amantadine treatment patients also reported an average “off time” decrease of .6 hours by week 12. Adversely, placebo patients reported an increase in average “off time” by .3 hours.
 
Researchers noted a maintained reduction in “duration, severity, and impact” of dyskinesia in amantadine patients through week 24, with UDRS score difference versus placebo patients reaching 9.3.
 
Nearly a quarter of amantadine patients reported visual hallucinations, peripheral edema, or dizziness as common adverse events during the trial, while very few to none placebo patients reported such effects. Treatment was discontinued for 13 (20.6%) amantadine patients, versus 4 (6.9%) placebo patients.
 
Researchers resolved the FDA-approved amantadine may be an effective treatment for LID, with a noted and possibility historic documentation of its supplemental effect on “off time.”
 
Shukla echoed the researchers’ report of LID efficacy, writing that among available oral medications, amantadine is “the sole drug to show a definite robust antidyskinetic effect.”

The study, "ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE LID Study)," was published online on the JAMA Neurology journal on June 12, 2017.

An editorial regarding the study — "Extended-Release Amantadine—A Smart Pill for Treatment of Levodopa-Induced Dyskinesia but Does the Evidence Justify the Cost?"— was made available online on the same day.

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