January 31, 2016
According to the results of a phase III clinical trial, a drug called opicapone may provide a new option for reducing “wearing-off” periods for people with Parkinson’s disease (PD) who take levodopa. The researchers found that opicapone is modestly more effective than entacapone (Comtan®, also an ingredient in Stalevo®), the drug most commonly prescribed today for this purpose. It also offers the convenience of only one dose a day. The study appears in the December 22 online edition of The Lancet Neurology.
For people with Parkinson’s, levodopa (usually prescribed as Sinemet®) is the most effective medication to treat movement symptoms. But after several years, most people find that the drug’s effects fluctuate – the levodopa wears off before it’s time for the next dose, and PD symptoms return.
Drugs called COMT inhibitors can extend the therapeutic effects of levodopa. Of the two drugs in this class available today, entacapone is safe but increases “on” time for less than an hour a day, and tolcapone (Tasmar®) has longer-lasting effects but can be toxic to the liver. So the search is on for better COMT inhibitors.
For the new study, an international team of researchers led by Patricio Soares-da-Silva, M.D., Ph.D., at the Portuguese pharmaceutical company BIAL, compared the effects of treating “wearing-off” with three different doses of opicapone (a new COMT inhibitor), placebo and entacapone. They recruited 600 study participants at 106 specialist PD centers in 19 European countries and Russia. Participants were randomly assigned to the five treatment groups – taking either opicapone, entacapone or placebo alongside levodopa for 14 to 15 weeks. During this time, participants recorded their “off” time in daily diaries.
Results
- Of the three doses of opicapone tested, only the highest one (50 mg daily) reduced “off” time as effectively as the existing drug entacapone.
- Compared to placebo, opicapone 50 mg/day reduced "off" time by about 60 minutes a day, while entacapone reduced "off" time by 40 min a day.
- Taking opicapone increased the length of “on” time by a small amount leading to without troubling dyskinesias (involuntary movements).
- Opicapone was safe and well-tolerated.
What Does It Mean?
“Wearing off,” and the return of PD symptoms between levodopa doses, can seriously affect a person’s quality of life. When it develops, people with PD may need to start taking levodopa every three hours, or even more frequently.
Other types of drugs, including MAO-B inhibitors, COMT inhibitors and dopamineagonists, and forms of levodopa such as levodopa infusion and Rytary®, may help reduce “off” time. Deep brain stimulation is effective as well.
Despite these treatment options, “wearing off” can be a serious problem, negatively affecting the quality life of people with PD. If future clinical trials have similar results to this study, and if the FDA eventually approves opicapone, this drug will provide doctors and people with PD an additional way to cope with “wearing off” in PD. Opicapone was only modestly more effective at reducing “off” time than entacapone, but it has the simplicity and convenience of a once-a-day dose.
Researchers continue to investigate ways to improve COMT inhibitors and their use. For example, more studies are needed to find out whether taking opicapone before levodopa fluctuations start could delay their onset. Also, it may be that some people are genetically predisposed to benefit more from this and other COMT inhibitors.
Reference: Ferreira JJ, Lees A, Rocha J-F, Poewe W, Rascol O, Soares-da-Silva P. (2015) Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations:
a randomised, double-blind, controlled trial. Lancet Neurology http://dx.doi.org/10.1016/S1474-4422(15)00336-1
http://www.pdf.org/en/science_news/release/pr_1454252421
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