Long-term safety and efficacy of acotiamide in functional dyspepsia (postprandial distress syndrome)-results from the European phase 3 open-label safety trial.

BACKGROUNDS: Acotiamide is a novel acetylcholinesterase inhibitor for treatment of postprandial distress syndrome (PDS) symptoms of functional dyspepsia (FD). This European phase 3 open-label safety trial has been conducted to evaluate the long-term safety of acotiamide and explore the efficacy of acotiamide on PDS symptoms using the validated LPDS, quality of life using SF-36 and SF-NDI, and work productivity using WPAI. METHODS: FD-PDS patients (defined by ROME III criteria) aged ≥18 years with active PDS symptoms and without predominant overlapping symptoms of epigastric pain syndrome and related disorders were enrolled to receive 100 mg acotiamide three times daily for 1 year. Patients' safety profile and efficacy of acotiamide were monitored. KEY RESULTS: The majority of patients (81.6%) maintained exposure to acotiamide for >50 weeks, with a mean duration of 320.3 days. No specific clinically significant safety concerns have been shown, with no deaths, treatment-related severe/serious adverse events, or any clinically significant laboratory test results. Although being an open-label trial, acotiamide showed a change in severity larger than the minimum clinically important difference at weeks 1 and 2 for postprandial fullness and early satiation (meal-related symptoms), and showed improvement of quality of life and work productivity from the first measurement (at week 12) up to 1 year. CONCLUSIONS & INFERENCES: The long-term safety of acotiamide treatment was confirmed. A clinically important change for PDS symptoms, QoL, and work productivity was suggested; however a controlled trial is required to confirm this hypothetic efficacy of acotiamide. (NCT01973790).

An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus.

Atacicept, a recombinant fusion protein containing the extracellular, ligand-binding portion of the transmembrane activator and calcium modulator and cyclophilin-ligand interactor receptor, and the Fc portion of human immunoglobulin (Ig) G, is designed to block the activity of B-lymphocyte stimulator and a proliferation-inducing ligand, and may have utility as a treatment for B-cell-mediated diseases, such as systemic lupus erythematosus (SLE). This Phase Ib study investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of intravenous (i.v.) atacicept in patients with mild-to-moderate SLE. Patients (n = 24) were randomised (5:1) to receive atacicept (single dose: 3, 9 or 18 mg/kg; or multiple dose: 2 x 9 mg/kg) or matching placebo. Patients were followed for 6 weeks after dosing (9 weeks in the 2 x 9 mg/kg cohort). Local tolerability of atacicept was comparable with that of placebo, with only mild injection-site reactions reported with atacicept. Atacicept i.v. was generally well tolerated, both systemically and locally, in patients with mild-to-moderate SLE. Atacicept displayed non-linear PK, which was predictable across doses and between single and repeat doses. The biological activity of atacicept was demonstrated by its marked effect in reducing B-cells and Ig levels in patients with SLE. This supports the utility of this therapeutic approach in the treatment of autoimmune diseases, such as SLE.

Effects of Ramipril and Isradipin on hemorheological profiles in patients with arterial hypertension.

In this study, the effect of the angiotensin-converting-enzyme inhibitor (ACE inhibitor) Ramipril (5 mg/day) and calcium antagonist Isradipin (5 mg/day) treatment of two groups of hypertensive patients (n = 22 in each of group) was evaluated. The parameters of the hemorheological profile (blood and plasma viscosity, red blood cell aggregation and deformation, plasma protein concentration and its osmolality, hematocrit and ratio of Hct/blood viscosity) were measured in basal conditions (before treatment) and after 3 weeks of treatment. The patients showed some increased blood, plasma viscosity, RBC aggregability and fibrinogen concentration in basal conditions. In both groups of patients, three main parameters of the hemorheological profile (plasma viscosity, Hct and RBC aggregation) decreased after treatment. No significant changes in red cell deformability was found. In conclusion, ACE inhibition with Ramipril and calcium channel blocking with Isradipin lead to a moderate improvement of blood rheology in patients with hypertension. This may be explained by the pronounced vasodilatatory effect of ACE inhibitor and calcium antagonist, though their acting mechanism is different.