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)

Hierarchical planning for just in time deliveries

The just-in-time (JIT) delivery of products is a considerable challenge for many firms, because suitable planning methods have to be developed and practically installed. One main problem refers to the suppliers strategy, as they are no longer able to keep their optimal lot sizes and production rates due to customers reduced call-forward rates (cf. e.g. Fandel et al. 1988 and Fandel 1988). Thus, the suppliers have to choose different planning procedures in order to assure that there will be no avoidable in-process costs, as concerns particularly the production, inventory, and transportation of products. Obviously, there exist remarkable trade-offs between the design parameters of the whole process (cf. Reese 1991), which require a simultaneous optimization of all variables. Document type: Part of book or chapter of boo

Standing on the Shoulders of Dwarfs: the Kepler Asteroseismic LEGACY Sample. II. Radii, Masses, and Ages

23 pages, 14 figures, ApJ, acceptedInternational audienceWe use asteroseismic data from the Kepler satellite to determine fundamental stellar properties of the 66 main-sequence targets observed for at least one full year by the mission. We distributed tens of individual oscillation frequencies extracted from the time series of each star among seven modelling teams who applied different methods to determine radii, masses, and ages for all stars in the sample. Comparisons among the different results reveal a good level of agreement in all stellar properties, which is remarkable considering the variety of codes, input physics and analysis methods employed by the different teams. Average uncertainties are of the order of ~2% in radius, ~4% in mass, and 10% in age, making this the best-characterised sample of main-sequence stars available to date. We test the accuracy of the determined stellar properties by comparing them to the Sun, angular diameter measurements, Gaia parallaxes, and binary evolution, finding excellent agreement in all cases and further confirming the robustness of asteroseismically-determined physical parameters of stars when individual frequencies of oscillation are available. Baptised as the Kepler dwarfs LEGACY sample, these stars are the solar-like oscillators with the best asteroseismic properties available for at least another decade. All data used in this analysis and the resulting stellar parameters are made publicly available for the community