An extended-release formulation of amantadine is safe and effective for relieving troublesome dyskinesias in people with Parkinson’s disease (PD), according to a new study. The results appear in the June 12 online edition of JAMA Neurology. A decision on the drug’s approval by the US Food and Drug Administration (FDA) is expected this year, meaning it could be available to people with PD relatively soon.
After taking levodopa (Sinemet®) for several years, many people with PD develop involuntary movements called dyskinesias. They often occur when the drug is at its peak effectiveness. One drug that physicians can rely on to help control dyskinesias is amantadine (Symmetrel®); however, it has some side effects such as insomnia, that can be problematic. Because of this, researchers have developed a new experimental extended-release form of the drug, ADS-5102, they hope will overcome some of these limitations. Taken at bedtime, the drug’s effects peak the following day at a time when dyskinesias usually begin, and when insomnia (a side effect of amantadine) is not a problem.
Researchers led by Rajesh Pahwa, M.D., at the University of Kansas Medical Center in Kansas City, KS, tested the new formulation of amantadine in a large phase III A research study in humans that aims to test a new intervention – this could be a drug, surgery or therapy like exercise or diet guidelines – to make sure it is effective and safe.. They enrolled 126 people with PD who were on average 65 years old, had been diagnosed with PD for nine years, and experienced four and half hours/day of “on” time with troublesome dyskinesias. For 12 weeks, half of the study participants took 274 mg of ADS-5102 daily, and the other half took placebo capsules. The study was double blinded, meaning neither participants nor medical personnel knew who got which capsules.
- The experimental extended-release amantadine (ADS-5102) was generally well-tolerated, safe and effective.
- After 12 weeks, for people who took ADS-5102, the duration, severity and impact of participants’ dyskinesias were reduced by about 8 points more on a standard rating scale than they were for people who took a placebo.
- People who took ADS-5102 reduced their “off” time — time in between levodopa doses when the medication lost effectiveness — by about half an hour a day.
- Most participants taking ADS-5102 experienced mild to moderate side effects, including visual hallucinations, swelling of the feet and ankles, dizziness, dry mouth and constipation that stopped when stopping the medication. Because of side effects, 13 participants (more than 20 percent) taking ADS-5102 did not complete the study.
What Does It Mean?
The new study finds that a new form of amantadine, ADS-5102 may be a modestly effective treatment for levodopa-induced dyskinesias. Although the currently available formulation of amantadine — which is generic and immediate-release — has been available for nearly 50 years, it was never been tested in clinical trials with people with Parkinson’s. Because of this, in an editorial that accompanies the clinical trial report, Aparna Wagle Shukla, M.D., notes that more research is needed to compare the current version with the new extended-release ADS-5102. It is possible that amantadine, which must be taken two or three times a day, may also help dyskinesias, but at a lower cost.
The new, extended-release formulation of amantadine has the benefit of reducing “off” time in between levodopa doses with fewer pills. The US FDA is expected to make a decision on the drug’s approval before the end of the year. If approved, ADS-5102 would be the first drug approved specifically to treat dyskinesias in Parkinson’s.
Pahwa R, Tanner CM, Hauser RA, et al. (2017). ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE LID Study): A Randomized Clinical Trial. JAMA Neurology doi:10.1001/jamaneurol.2017.0943
Wagle Shukla A. (2017). Extended-Release Amantadine—A Smart Pill for Treatment of Levodopa-Induced Dyskinesia but Does the Evidence Justify the Cost? JAMA Neurology doi:10.1001/jamaneurol.2017.0954