3 research outputs found
Senicapoc treatment in COVID-19 Patients with Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial
BACKGROUND: The aim of the current study was to determine if treatment with senicapoc, improves the PaO(2)/FiO(2) ratio in patients with COVIDâ19 and severe respiratory insufficiency. METHODS: Investigatorâinitiated, randomized, openâlabel, phase II trial in four intensive care units (ICU) in Denmark. We included patients aged âĽ18âyears and admitted to an ICU with severe respiratory insufficiency due to COVIDâ19. The intervention consisted of 50âmg enteral senicapoc administered as soon as possible after randomization and again after 24âh. Patients in the control group received standard care only. The primary outcome was the PaO(2)/FiO(2) ratio at 72âh. RESULTS: Twenty patients were randomized to senicapoc and 26 patients to standard care. Important differences existed in patient characteristics at baseline, including more patients being on nonâinvasive/invasive ventilation in the control group (54% vs. 35%). The median senicapoc concentration at 72âh was 62.1âng/ml (IQR 46.7â71.2). The primary outcome, PaO(2)/FiO(2) ratio at 72âh, was significantly lower in the senicapoc group (mean 19.5 kPa, SD 6.6) than in the control group (mean 24.4 kPa, SD 9.2) (mean difference â5.1 kPa [95% CI â10.2, â0.04] p =â.05). The 28âday mortality in the senicapoc group was 2/20 (10%) compared with 6/26 (23%) in the control group (OR 0.36 95% CI 0.06â2.07, p =â.26). CONCLUSIONS: Treatment with senicapoc resulted in a significantly lower PaO(2)/FiO(2) ratio at 72âh with no differences for other outcomes
Pharmacokinetics and pharmacodynamics of cannabisâbased medicine in a patient population included in a randomized, placeboâcontrolled, clinical trial
Abstract Information on the pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered cannabisâbased medicine (CBM) in capsule formulation in patient populations is sparse. In this exploratory study, we aimed to evaluate the PK and PD in a probable steady state of CBM in neuropathic pain and spasticity in a population of patients with multiple sclerosis (MS). Of 134 patients participating in a randomized, doubleâblinded, placeboâcontrolled, trial, 23 patients with MS (17 female) mean age 52âyears (range 21â67) were enrolled in this substudy. They received oral capsules containing Î9âtetrahydrocannabinol (THC, nâ=â4), cannabidiol (CBD, nâ=â6), a combination (THC&CBD, nâ=â4), or placebo (nâ=â9). Maximum doses were 22.5âmg (THC) and 45âmg (CBD) a day divided into three administrations. PD parameters were evaluated for pain and spasticity. Blood samples were analyzed using an ultraâhighâperformance liquid chromatographyâtandem mass spectrometer after protein precipitation and phospholipid removal. PK parameters were estimated using computerized modeling. The variation in daily dose and PK between individuals was considerable in a steady state, yet comparable with previous reports from healthy controls. Based on a simulation of the best model, the estimated PK parameters (mean) for THC (5âmg) were Cmax 1.21âng/mL, Tmax 2.68âh, and halfâlife 2.75âh, and for CBD (10âmg) were Cmax 2.67âng/mL, Tmax 0.10âh, and halfâlife 4.95âh, respectively. No effect was found on the PD parameters, but the placebo response was considerable. More immediate adverse events were registered in the active treatment groups compared with the placebo group