Objective: To evaluate, in levodopa-treated Parkinson’s Disease (PD) patients with ‘early’ motor fluctuations, the proportion of patients (ie, responders) achieving at least a 1-h reduction in absolute time in the OFF-state or at least a 1-h increase in absolute total time in the ON-state.

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 (AE) during the first 3 weeks of treatment, investigators could titrate down the daily dose of levodopa. The primary efficacy variable was the change from baseline in absolute OFF-time based on patient diaries. Key secondary analysis was the proportion of OFF-time responders, defined as subjects experiencing at least one hour of OFF-time reduction [1]. ‘Early fluctuators’ were defined as subjects with an onset of motor fluctuation within <2 years of study baseline. This post-hoc subgroup analysis investigated the ON- and OFF-time responders of OPC-50mg compared with entacapone (ENT) and placebo (PLC), in levodopa-treated patients with PD and considered as ‘early fluctuators’.

Results: A total of 359 patients were randomized to 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, compared with PLC (48%), the OFF-time responders was significantly higher in OPC-50mg (70%, p=0·001) group. The ON-time responders was also significantly higher in the OPC-50mg (65%, p=0·003) when compared with PLC (46%). No significant differences were noted in both OFF- (58%) and ON-time (58%) responders for ENT versus PLC. For the ‘early fluctuators’, compared with PLC (47%), the OFF-time responders was significantly higher in OPC-50mg (69%, p=0·0157). The ON-time responders was also significantly higher in the OPC-50mg (66%, p=0·0061) when compared with PLC (42%). No significant differences were noted in both OFF- (56%) and ON-time (56%) responders for ENT versus PLC.

Conclusions: Similar to the total study population, OPC-50mg was effective in reducing motor fluctuations in patients considered ‘early fluctuators’ resulting in a similar and significant proportion of patients (ie, responders) achieving at least a 1-h reduction in absolute time in the OFF-state and/or at least a 1-h increase in absolute total time in the ON-state.

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-responder-analyses-from-the-bipark-i-double-blind-experience/