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

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)

Diffusion and perfusion imaging in acute diagnostics of cerebral ischaemia

Potenzielle Therapieformen der zerebralen Ischämie zielen vor allem auf die Rettung der Penumbra, welche potentiell rettbares Gewebe darstellt. Daraus ergibt sich die Frage, ob die Akutdiagnostik eine Darstellung von Kern und Penumbra leisten kann. Die Computertomographie als derzeitiger Goldstandard wird diesen Anforderungen nicht gerecht. Ihre wesentliche Rolle liegt im differenzial-diagnostischen Ausschluss einer Blutung. Neue funktionell orientierte kernspintomographische Verfahren, die möglicherweise dem Anspruch einer Definition der Penumbra gerecht werden, sind die Diffusionsbildgebung (DWI) und die Perfusionsbildgebung (PWI). Viele Studien mit DWI erbrachten Hinweise, dass in der Akutphase das Gebiet mit verminderter Wasserdiffusion als Maß für den Infarktkern dienen kann. Eine Reihe von Autoren schlugen vor, dass eine Verlängerung der mittleren Transitzeit in der PWI (abzüglich der Region des Infarktkerns) als Maß für die Penumbra angesehen werden kann. Obwohl diese Arbeitsdefinition eine erste Annäherung an eine pathophysiologische Charakterisierung in der Akutphase darstellt, gibt es zunehmend Hinweise, dass diese Definition in Zukunft eine erhebliche Modifikation erfahren muss. Unter Nutzung von verbesserten Auswertestrategien halten wir jedoch für die Zukunft therapeutische Entscheidungen basierend auf diesen neuen Verfahren für wahrscheinlich