Session Information
Date: Saturday, October 6, 2018
Session Title: Parkinson’s Disease: Clinical Trials, Pharmacology And Treatment
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: To assess the occurrence of dopaminergic adverse-events (AEs) in levodopa-treated COMT-naïve Parkinson’s Disease (PD) patients when starting opicapone (OPC) 50mg or entacapone (ENT).
Background: OPC, a new 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: Double-blind, 14 to 15-week, placebo- and active-controlled study. In the emergence of dopaminergic-AEs during the first 3-weeks, investigators could titrate the levodopa daily-dose. Dopaminergic-AEs were defined as new or worsening post-baseline treatment. This post-hoc analysis investigated the dopaminergic-AEs occurrence, namely, dyskinesia, nausea, hallucinations (including delusion, illusion and disturbance-in-attention), vomiting and orthostatic hypotension.
Results: A total of 359 patients were randomized to placebo (PLC, n=121), OPC-50mg (n=116) or ENT (n=122). Cumulatively, patients taking OPC-50mg reported more dopaminergic-AEs (22%) compared to ENT (16%) and PLC (8%). Subjects with dopaminergic-AEs took levodopa ≥700mg/day (on average). Cumulatively, by the end of double-blind, cases of dyskinesia, nausea, hallucination, vomiting and orthostatic hypotension were reported, respectively, by 5%, 1%, 2%, 1% and 0% under PLC; 10%, 11%, 1%, 0% and 2% under ENT; and 17%, 3%, 8%, 1% and 1% under OPC-50mg. However, despite no levodopa-adjustment during last 3-months, the actual (by-day) frequency was 2%, 1%, 0%, 0% and 0% under PLC; 3%, 1%, 0%, 0% and 1% under ENT; and 4%, 0%, 0%, 0% and 0% under OPC-50mg, respectively. Under OPC-50mg, dyskinesia presented an earlier onset than hallucinations. Dyskinesia appear to have a later onset under ENT versus OPC-50mg.
Conclusions: There was an apparent treatment-relationship for dopaminergic-AEs with OPC presenting the highest incidence. These observations support an enhanced dopaminergic efficacy of OPC and whilst dyskinesia could be managed by an early follow-up, hallucinations may require a later-stage follow-up.
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.
To cite this abstract in AMA style:
K. Chaudhuri, A. Sauerbier, J. Ferreira, F. Stocchi, E. Arbe, J-F. Rocha, P. Soares-da-Silva. Occurrence of dopaminergic adverse-events in COMT-naïve patients starting adjunctive therapy with opicapone: The BIPARK-I double-blind experience [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/occurrence-of-dopaminergic-adverse-events-in-comt-naive-patients-starting-adjunctive-therapy-with-opicapone-the-bipark-i-double-blind-experience/. Accessed May 21, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/occurrence-of-dopaminergic-adverse-events-in-comt-naive-patients-starting-adjunctive-therapy-with-opicapone-the-bipark-i-double-blind-experience/