Purpose: A large proportion of patients with Mb. Parkinson’s disease experiences fluctuations in the effect of levodopa therapy during the course of the disease.
To inhibit peripheral levodopa metabolism via catechyl-0-metyhltransferase (COMT), two COMT inhibitors with very limited efficacy and applicability have been available to date: Entacapone leads to reduction of daily OFF time of only about 40 min. and tolcapone is recommended only as second-line therapy because of its hepatotoxic potential. Opicapone is a novel, long-acting COMT inhibitor with promising performance in Phase III trials (BIPARK, BRIVARACT-I).
Methods: The BRIVARACT-II is a study of the efficacy and safety of opicapone 25 mg and 50 mg in more than 400 Parkinson’s disease patients up to Hoehn & Yahr stage III from 71 centers in 12 countries with effect fluctuations under conventional Parkinson’s therapy. A double-blind, randomized, placebo-controlled phase lasting 3-4 months was followed by an open-label phase lasting 1 year.
Results: At the end of the blinded phase, there was a reduction in off-time (root mean square) of 65 min. In the placebo group, 102 min. in the 25 mg and 119 min. in the 50 mg opicapone group, with only the 50 mg group reaching the significance level. At the end of the off-label phase, the off-time reduction remained constant. Other scale-based or patient-oriented outcome criteria had no significant effect. The most common side effects were dyskinesia, constipation, and dry mouth, roughly comparable in all groups. Serious adverse events occurred slightly more frequently in the 50 mg group (6% vs 3-4%) and discontinuation in 12%, significantly less in the 25 mg and placebo groups.
Author’s conclusion: Opicapone is a future COMT inhibitor at least equal in efficacy to the current options and superior in safety for the treatment of motor fluctuations in moderately advanced Mb. Parkinson’s available. The effective reduction of daily OFF time by almost 1 hour, despite an unusually large placebo effect, is relevant and the only once-daily intake is patient-friendly. Opicapone has already been approved by the EMA and will soon be available in Switzerland.
InFo NEUROLOGY & PSYCHIATRY 2017; 15(2): 26.
