New Support for Therapy that Reduces "Off" Time

A new study finds that the experimental drug opicapone significantly reduces “off” time for people with Parkinson’s disease (PD) who experience fluctuations in the effectiveness of their levodopa medications. The results of this phase III clinicaltrial appear in the December 27, 2016, online edition of JAMA Neurology.

Levodopa is the gold standard medication for PD movement symptoms. But after several years of taking this drug, many people find that its effects wear off between doses. Drugs called COMT (catechol-o-methyl transferase) inhibitors can extend levodopa’s benefits. But the two COMT inhibitors that are currently available have shortcomings: entacapone is safe but extends “on” time for less than an hour a day, and needs to be taken frequently; tolcapone (Tasmar®) has longer-lasting effects but can be toxic to the liver and require liver enzyme monitoring.

For the new study, an international team of researchers led by Andrew J. Lees, M.D., at the Reta Lila Weston Institute, University College London, London, compared the effects of treating wearing-off with two different doses of a newly developed COMT inhibitor. The double-blinded trial included 427 people with mild to moderate PD symptoms who experienced a minimum of 90 minutes of “off” time per day. Study participants were divided into three groups, taking either 25 mg opicapone, 50 mg opicapone or a placebo pill once a day for 14 or 15 weeks in addition to their standard PD medications. At the end of this period, the study was continued “open label” for another year, meaning that both medical staff and study participants were told who was getting what medication.


  • Study participants who took 50 mg/day of opicapone reduced their “off” time by about an hour a day.
  • The reduction in “off” time for the 50 mg/day group was sustained throughout the year of “open-label” use of the drug.
  • The 25 mg/day dose of opicapone was no more effective than placebo.
  • Although opicapone was generally well tolerated, side effects included dyskinesia, constipation and dry mouth.
  • Participants had fewer incidents of severe diarrhea and liver toxicity with opicapone compared to other COMT inhibitors.

What Does It Mean?

This clinical trial found that a 50 mg dose of opicapone compares well, in terms of safety and effectiveness, with other COMT inhibitors that are currently available. Earlier clinical trials have reported similar results, and the drug was approved for use in Europe in July 2016.

The authors of an editorial that accompanies the research paper note that the once-a-day dosing may make opicapone easier and more practical for people with PD to use, and also allow doctors to fine-tune levodopa dosing more readily. They further recommend a “back to back” study comparing opicapone to other COMT inhibitors. The major limitation of the drug is that as expected, it increased the frequency of dyskinesia. The Parkinson’s community urgently needs therapies that increase “on” time without worsening dyskinesia.

That said, if approved by the US Food and Drug Administration, opicapone will provide people with PD and their doctors a new option to consider for reducing “off” time.


Lees AJ, Ferreira J, Rascol O, Poewe W, Rocha J-F, McCrory M, Soares-da-Silva P. (2016). Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurology doi:10.1001/jamaneurol.2016.4703

Boyle A, Suescun J, Schiess MC. (2016). Opicapone: A Novel Adjunct for an Old Standard. JAMA Neurology published online December 27, 2016


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