Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: the OPTIPARK open-label study

Abstract

Background: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials.

Methods: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson's disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician's Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).

Results: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: - 3.0 ± 4.6, p < 0.0001) and motor scores during ON (- 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of - 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients.

Conclusions: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice.

Trial registration: Registered in July 2016 at clinicaltrials.gov (NCT02847442).

Keywords: Levodopa; Motor fluctuations; Open-label; Opicapone; Parkinson’s disease.

Conflict of interest statement

HR reports acting on Advisory Boards, gave lectures and received research grants from Abbott, Abbvie, Bayer Health Care, BIAL, Boehringer/Ingelheim, Brittania, Cephalon, Desitin, GSK, Lundbeck, Medtronic, Merck-Serono, Novartis, Orion, Pfizer, TEVA, UCB Pharma, Valeant, and Zambon. AJL is funded by the Reta Lila Weston Institute of Neurological Studies, University College London, Institute of Neurology and reports consultancies from Britannia Pharmaceuticals and BIAL. He also reports grants and/or research support from the Frances and Renee Hock Fund and honoraria from Britannia Pharmaceuticals, Profile Pharma, UCB, Roche, BIAL, STADA, Nordiclnfu Care, and NeuroDerm. JFR, DM and PSS are employed by BIAL - Portela & Cª, S.A.

Figures

Fig. 1

Patient disposition

Fig. 2

Global Impression of Change following 3 months treatment with opicapone 50 mg (LOCF) (a) investigator rated (CGI-C, n = 477); (b) self-rated by the patient (PGI-C, n = 393)

Fig. 3

Presence of PD symptoms as assessed on the WOQ-9 in patients who completed 3 months of study