Objective: To evaluate the impact on UPDRS-II and III in levodopa-treated Parkinson’s Disease (PD) patients with ‘early’ motor fluctuations.

Background: Opicapone (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 (DB), 14 to 15-week, placebo- and active-controlled study. In the emergence of dopaminergic-related adverse events (AE) 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 [1]. ‘Early fluctuators’ were defined as subjects with an onset of motor fluctuation within <2 years of study baseline. This subgroup analysis investigated the change in UPDRS-II and III at the end of the DB of the OPC-50mg, entacapone (ENT), and placebo (PLC) groups, in levodopa-treated patients with PD and considered as ‘early fluctuators’. Data was analyzed via an ANCOVA model with treatment group and region as fixed effects.

Results: A total of 359 patients were randomized to placebo (PLC, n=121), OPC-50mg (n=116) or ENT (n=122). From these, 206 patients were ‘early fluctuators’ (PLC, n=66), OPC-50mg (n=70) or ENT (n=70). Overall, by the end of the DB period, the post-baseline UPDRS-II and III total scores decreased in all treatment groups, indicating less disability in both non-motor and motor domains, respectively. The LS mean changes of UPDRS-II from DB baseline were -2.4, -3.1 and -3.0 for PLC, ENT and OPC-50mg, respectively. The LS mean changes of UPDRS-III from DB baseline were -3.7, -4.4 and -4.5 for PLC, ENT and OPC-50mg, respectively. For the ‘early fluctuators’, the LS mean changes [95%CI] of UPDRS-II from DB baseline were -2.6 [-3.8,-1.4], -3.2 [-4.4,-2.1] and -3.4 [-4.5,-2-2] for PLC, ENT and OPC-50mg, respectively. The LS mean changes [95%CI] of UPDRS-III from DB baseline were -3.3 [-5.1,-1.5], -3.9 [-5.7,-2.2] and -4.7 [-6.5,-2.9] for PLC, ENT and OPC-50mg, respectively.

Conclusions: Similar to the total study population, the addition of OPC-50 mg to PD patients considered as ‘early fluctuators’ reduced disability in both non-motor and motor domains, as assessed by UPDRS-II and III.

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/efficacy-of-opicapone-in-parkinsons-disease-patients-with-early-motor-fluctuations-updrs-ii-and-iii-analysis-from-the-bipark-i-double-blind-experience/