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).
| Original language | English |
|---|---|
| Article number | 9 |
| Journal | Translational Neurodegeneration |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 04.03.2020 |
Funding
The study was funded by BIAL. Three authors (JFR, DM and PSS) were employed by the funder and participated in the study design, data collection, data management, and data analysis. The funder of the study had no other role in data interpretation or in the decision to submit the manuscript for publication. BIAL also supported reporting of study results by procuring medical writing support. We thank the study staff and patients involved in the trial. Medical writing support (literature searching, preparation of tables, styling of the manuscript) was provided by Dr. Anita Chadha-Patel (ACP Clinical Communications) funded by BIAL. OPTIPARK Study Investigators group: Germany: Csaba Antal Zolnai, Claudius Bartels, Andreas Barth, Kriemhild Barth, Stephan Behrens, Arnfin Bergmann, Ralf Bodenschatz, Rommy Born,Moriz Brandt, Sebastian Brock, Bernd Brockmeier, Christof Br?cke, Norbert Br?ggemann, Bernhard B?hler, Uwe Bungard, Lukas Cepek, Ilona Csoti, Max Deist, Carl Detlev Reimers, Ulrich D?lle, Sylke Domke, Imanuel Dzialowski, Georg Ebersbach, Heike Eggert, Karla Eggert, Reinhard Ehret, Jana Engel, Urban Fietzek, Anke Friedrich, Michael Fritzinger, Florin Gandor, Klaus Gehring, Stephan Gierer, Stephanie Gierer, Vasil Gjaurov, Doreen Gruber, ?zkan G?nes, Thomas Haas, Kirsten Hahn, Anna Eszter Haraszti, Rolf Hartmann, Bernhard Haslinger, Eva Heiss, Heinz P. Herbst, Frank Hoffmann, Werner E. Hofmann, G?nter H?glinger, Wolfgang Jost, Anna-Maria Kavcic, Christoph Kellinghaus, Bertold Klemperer, Fabian Klostermann, Thomas Knoll, Natalia Koleva-Alazeh, Jiri Koschel, Diana Waltraud Kraft-Safavi, Almut Kronenberger, Andrea K?hn, Andreas Kupsch, Thomas Lehnhoff, Peter Laumen, Paul Lingor, Karla Lippmann, Michael Lorrain, Fabian Maass, Siegfried Muhlack, Thomas M?ller, Michael Nagel, Stephan Neudecker, Katja Odin, Christian Oehlwein, Hakan Orbasli, Wolfram von Pannwitz, Heidi Pape, Robert Pfister, Tino Prell, Reinhard Puzich, Daniela Rau, Rene Reese, Gerd Reifschneider, Gernot Reimann, Stefani Ries, Christoph Rieth, Charlotte Rewitzer, Ali Safavi, Alexander B. Schmied, Johannes Schwarz, Wolfgang Schwarz, Joachim Springub, Inga Suttrup Claus, Vera Tadic, Klaus Tiel- Wilck, Lars T?nges, Jens Tr?ger, Christoph Schrey, Alexander Schulze, Sven Thonke, Tobias W?chter, Achim S. Wannenmacher, Tobias Warnecke, Bettina Wieder, Martin Wimmer, Christian Winkler, Otto Witte, Dirk Woitalla, Samis Zella, Uwe Ziebold. UK: Jane Alty, Reem Amin, Michaela Boca, Stephen Butterworth, Camille Carroll, Gavin Charlesworth, K. Ray Chaudhuri, Rajkumar Chinnadurai, Jemima Collins, Jeremy Stephen Cosgrove, Samantha Cravey, Dinesh Damodaran, Nikolay Dimitrov, Rory Durcan, Simon Ellis, Adbdul Elmarimi, Jonathan Evans, James Fisher, Donald Grosset, Stuart Jamieson, Christopher Kobylecki, Sze Hway Lim, Veronica Lyell, Biju Mohamed, Sophie Molloy, Nicola Pavese, Dominic Paviour, Madeleine Purchas, Khalid Rashed, Christopher Rickards, Tabish Saifee, Gillian Sare, Christine Schofield, Naveen Setty, Jagdish Sharma, Ray Sheridan, Siew Lee Shu, Monty Silverdale, Rani Sophia, Sarah Statton, Malcolm Steiger, Christopher Thomas, Richard Walker, Tai Yen Foung.
