Objective: To evaluate the efficacy of opicapone (OPC) in levodopa-treated Parkinson’s Disease (PD) patients with motor fluctuations and subdivided by their baseline OFF-time.

Background: OPC, a novel once-daily COMT inhibitor, has shown to be effective in the treatment of motor fluctuations in PD patients in two large, pivotal, multinational trials (BIPARK-I and II) [1,2]

Methods: Multinational, multicentre, double-blind, 14 to 15-week, placebo- and active-controlled study. In the emergence of dopaminergic-related adverse-events during the first 3-weeks of treatment, investigators could titrate down the daily dose of levodopa. Dopamine-agonists (DA) and MAO-B inhibitors (MAO-Bi) used for the treatment of PD were also allowed provided their dosage remained stable for at least 4-weeks before and throughout the study. The primary efficacy variable was the change from baseline in absolute OFF-time based on patient diaries [1]. This post-hoc subgroup analysis investigated the efficacy of OPC-50mg and entacapone (ENT), in levodopa-treated patients with PD who were subdivided by their baseline OFF-time (ie., >90 mins and every additional 30 mins interval up to an interval with a minimum sample size of 40 patients in at least one arm). Results are based on a linear model with treatment groups and baseline OFF-time and Region as co-variates.

Results: A total of 238 patients were randomized to OPC-50mg (n=116) or ENT (n=122). In all subgroup intervals, OPC-50mg presented a greater OFF-time reduction than ENT. Subjects with a higher baseline OFF-time had a greater response under both OPC-50mg and ENT. There was, on average, a difference of -26.6 mins OFF-time reduction favoring OPC-50mg. The estimated difference favoring OPC-50mg increased with increasing baseline OFF-time, reaching statistically significance (p<0.05) for subjects with >390 mins baseline OFF-time (~ -50 mins difference to ENT).

Conclusions: Subjects with a higher baseline OFF-time had a greater response under both OPC-50mg and ENT. OPC-50mg presented a greater OFF-time reduction than ENT for all subgroup intervals, reaching statistically significance for subjects with >390 mins baseline OFF-time (~ -50 mins difference to ENT).

References: 1. Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P, et al. 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 Neurol 2016;15:154-165. 2. Lees AJ, Ferreira J, Rascol O, Poewe W, Rocha JF, McCrory M, et al. Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol 2017;74:197-206.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/influence-of-baseline-off-time-in-the-efficacy-response-of-opicapone-in-parkinsons-disease-patients-with-motor-fluctuations-the-bipark-i-double-blind-experience/