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)

Thermodynamique des systèmes composés de gaz acides, d'eau et de sels sous hautes pressions et aux températures moyennement élevées

L'objectif principal de ce travail de thèse est l'acquisition et l'interprétation de nouvelles données thermodynamiques concernant les gaz acides (CO2 et H2S) et nécessaires à la modélisation de procédés de séquestration en aquifère salins. A cette fin, nous avons développé une technique de calorimétrie à écoulement qui permet d'accéder simultanément aux données enthalpiques et aux solubilités du CO2 et du H2S dans des solutions salines. Au cours de ce travail une nouvelle unité de mélange a été developpée et utilisée avec succès dans des conditions extrêmes : jusqu'à 393 K, avec des solutions salines fortement concentrées (solutions de NaCl et de CaCl2 de forces ioniqies jusqu'à 5 m) et des pressions de H2S jusqu'à 30 MPa. Le but était d'étudier l'influence de la pression, de la température, de la nature et de la concentration du sel sur la solubilité et les effets enthalpiques. La comparaison avec les données de la littérature combinée avec une analyse d'erreur d' "apriori" suggère que l'erreur sur l'enthalpie soit d'environs 4-5% et typiquement de 6-7% sur la détermination de la solubilitéCLERMONT FD-BCIU Sci.et Tech. (630142101) / SudocSudocFranceF

Enthalpy and Solubility Data of H2S in Water at Conditions of Interest for Geological Sequestration

International audienceThe dissolution of hydrogen sulfide in water was studied by measuring the heat of mixing ¢Hmix at conditions of interest for geologic storage of acid gases in deep aquifers. The measurements were performed with a new mixing unit equipped with a Hastelloy tubing, developed specifically for an isothermal differential heat flux calorimeter of Setaram. The heats of mixing were determined at target temperatures of 323, 353, and 393 K and pressures up to 31 MPa in the regions where the solution is unsaturated or saturated by H2S, that is, gaseous, liquid, or supercritical states. The concentration dependence of ¢Hmix allowed the simultaneous determination of the limiting enthalpy of solution ¢Hsol and the gas solubility limit. The agreement between our solubility results and the data from the direct phase equilibrium measurements reported in literature was good. Although no calorimetric data exist for verifying the correctness of ¢Hsol values, their internal consistency was tested by conversion to the low pressure enthalpies of hydration ¢Hhyd. These values agreed reasonably well with those derived from the temperature derivative of the Henry's law constants calculated from representative correlations in the literature. The solubility and enthalpic data for aqueous H2S as a function of temperature and pressure were compared with analogous data for CO2 in water that we have published earlier

Experimental determination of enthalpy of dissolution and solubility of CO2 in aqueous 2-amino-2-methyl-1-propanol (AMP)

Communication oral

Thermodynamic data for carbon dioxyde. Dissolution in aqueous NaCl solutions

Communication oral