Affiliations: [a] University College London, Reta Lila Weston Institute, London, UK
| [b] Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal
| [c] CNS – Campus Neurológico Sénior, Torres Vedras, Portugal
| [d] Department of Research and Development, BIAL – Portela & Ca SA, S. Mamede do Coronado, Portugal
| [e] Department of Clinical Pharmacology and Neurosciences, INSERM and University Hospital of Toulouse, Toulouse, France
| [f] Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
| [g] Department of Pharmacology and Therapeutics, Faculty of Medicine, University Porto, Porto, Portugal
| [h] MedInUP, Center for Drug Discovery and Innovative Medicines, University Porto, Porto, Portugal
Correspondence to: Professor P. Soares-da-Silva, Department of Research and Development, BIAL, A Av. da Siderurgia Nacional, 4745-457S. Mamede do Coronado, Portugal. Tel.: +351 229866100; Fax: +351 229866192; E-mail: [email protected].
Abstract: Background:Opicapone is a catechol O-methyltransferase (COMT) inhibitor indicated for use as adjunct to levodopa therapy in patients with Parkinson’s disease (PD) and motor fluctuations. Objective:To characterize the safety and tolerability of adjunct opicapone (25 and 50 mg) in a pooled population of levodopa-treated PD patients who participated in the opicapone Phase-3 clinical program. Methods:Patient-level data (placebo, opicapone 25 mg and 50 mg) from the BIPARK-1 and BIPARK-2 double-blind and open-label studies were combined. Results:Pooled analyses included 766 patients from the double-blind studies and 848 patients from the open-label studies. In the double-blind studies, 63.3% of opicapone-treated patients reported treatment-emergent adverse events (TEAEs) versus 57.2% in the placebo group. The most common TEAEs reported in the opicapone group compared to placebo were dyskinesia, constipation and insomnia. The incidence of serious TEAEs was similar across opicapone and placebo groups (3.5% versus 4.3%, respectively). Overall, 71.3% patients treated with open-label opicapone reported at least one TEAE; most occurred within the first 2 months of the open-label studies, and then decreased thereafter. Throughout the Phase-3 clinical program, there were no serious AEs suggestive of hepatic toxicity, and the incidence of gastrointestinal disorders such as nausea and diarrhea remained low (<2%). There were no relevant changes in laboratory parameters including liver enzymes, vital signs, physical or neurological examinations, or ECG readings. Conclusions:Long-term use of opicapone once-daily over 1-year at doses of 25 mg or 50 mg was generally safe and well tolerated, supporting its clinical usefulness in the management of PD motor fluctuations.
Keywords: Clinical trials, motor fluctuations, opicapone, Parkinson’s disease, safety