Efficacy and safety of opicapone, a new COMT-inhibitor, for the treatment of motor fluctuations in Parkinson's Disease patients: BIPARK-II study

Abstract

WCN 2013 No: 1034 Topic: 2 — Movement Disorders Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics, motor response, and erythrocyte-COMT activity in Parkinson's patients co-administered with levodopa/dopa-decarboxylase inhibitor J.J. Ferreira, J.-F. Rocha, A. Falcao, R. Pinto, T. Nunes, P. Soares-da-Silva. Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal; Research & Development, BIAL-PortelaC Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Dept. of Pharmacology & Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal Background: Opicapone (OPC) was developed to fulfil the need for more potent, safer and longer acting COMT inhibitors. Objectives: Investigate the effect of once-daily 5, 15 and 30 mg OPC, a new COMT inhibitor, on the levodopa pharmacokinetics, in Parkinson's Disease (PD) patients with motor fluctuations treated with standardrelease 100/25 mg levodopa/carbidopa (LC) or levodopa/benserazide (LB). Methods: This was a multicentre, double-blind, randomised, placebocontrolled study in four parallel groups of PD patients treated with LC or LB and with motor fluctuations (“wearing-off” phenomenon). Subjects were sequentially and randomly assigned to be administered, once-daily, during the 21 to 28 day maintenance phase with placebo or 5, 15 and 30 mg OPC. Subjects performed two levodopa tests, one on the morning of the day after admission and another following themaintenance phase. Subjects also kept a diary to record ON/OFF periods. Results: In relation to placebo, levodopa exposure increased 24.73%, 53.93% and 65.61% following 5, 15 or 30 mg OPC. Maximum S-COMT inhibition (Emax) ranged from 52% (5 mg OPC) to 80% (30 mgOPC). The study was not designed to detect any significant differences in motor performance, but the exploratory analysis performed shows improvement in various motor outcomes, including a dose dependent change in absolute OFF time corresponding to a percentage decrease of 0.77%, 4.16%, 29.55% and 32.71% with placebo, 5 mg, 15 mg and 30 mg OPC, respectively. Conclusion: OPC is a promising new COMT inhibitor and deserves further clinical evaluation in larger samples of patients with PD on levodopa treatment with motor fluctuations. doi:10.1016/j.jns.2013.07.390 Abstract — WCN 2013 No: 1038 Topic: 2 — Movement Disorders Efficacy and safety of opicapone, a new COMT-inhibitor, for the treatment of motor fluctuations in Parkinson's Disease patients: BIPARK-II study WCN 2013 No: 1038 Topic: 2 — Movement Disorders Efficacy and safety of opicapone, a new COMT-inhibitor, for the treatment of motor fluctuations in Parkinson's Disease patients: BIPARK-II study A. Lees, J.J. Ferreira, R. Costa, J.-F. Rocha, C. Oliveira, N. Lopes, T. Nunes, P. Soares-da-Silva. National Hospital for Neurology and Neurosurgery, London, UK; Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal; Research & Development, BIAL-Portela & Co. S.A., S. Mamede Coronado, Portugal; Dept. of Pharmacology & Therapeutics, Faculty of Medicine, University of Porto,