Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

HEMA/MMA/EDMA packing material evaluation for size exclusion chromatography (SEC)

HEMA/MMA/EDMA (2-hydroxyethyl methacrylate/methyl methacrylate/ethyleneglycol methacrylate) copolymer beads have been synthesized for use in aqueous SEC. This porous chromatographic support consisted of a large average particle size (250 µm) and contained macropores with a median pore size of approximately 880 Å. The material was packed in glass and stainless columns to assess their chromatographic performance. The packed columns were calibrated using narrow molecular weight (MW) distribution standards (dextran) and exhibited a range of molecular weight separation between 40,000 and 2,000,000 daltons. The packing material showed the ability to separate large molecules through the size exclusion mechanism

HPMA and HEMA copolymer bead interactions with eukaryotic cells

Two different hydrophilic acrylate beads were prepared via aqueous suspension polymerization. Beads produced of a hydroxypropyl methacrylate (HPMA) and ethyleneglycol methacrylate (EDMA) copolymer were obtained using a polyvinyl alcohol suspending medium. Copolymers of 2hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA) and ethyleneglycol methacrylate (EDMA) beads were obtained using magnesium hydroxide as the suspending agent. Following characterization by scanning electron microscopy (SEM), nitrogen sorption analysis (NSA) and mercury intrusion porosimetry (MIP), the beads were cultured with monkey fibroblasts (COS7) to evaluate their ability to support cell growth, attachment and adhesion. Cell growth behavior onto small HPMA/EDMA copolymer beads and large HEMA/MMA/EDMA copolymer beads is evaluated regarding their hidrophilicity/hidrophobicity and surface roughness

Controlled release from triple layer, donut-shaped tablets with enteric polymers

The purpose of this research was to evaluate triple layer, donut-shaped tablets (TLDSTs) for extended release dosage forms. TLDSTs were prepared by layering 3 powders sequentially after pressing them with a punch. The core tablet consisted of enteric polymers, mainly hydroxypropyl methylcellulose acetate succinate, and the bottom and top layers were made of a water-insoluble polymer, ethyl cellulose. Drug release kinetics were dependent on the pH of the dissolution medium and the drug properties, such as solubility, salt forms of weak acid and weak base drugs, and drug loading. At a 10% drug loading level, all drugs, regardless of their type or solubility, yielded the same release profiles within an acceptable level of experimental error. As drug loading increased from 10% to 30%, the drug release rate of neutral drugs increased for all except sulfathiazole, which retained the same kinetics as at 10% loading. HCl salts of weak base drugs had much slower release rates than did those of neutral drugs (eg, theophylline) as drug loading increased. The release of labetalol HCl retarded as drug loading increased from 10% to 30%. On the other hand, Na salts of weak acid drugs had much higher release rates than did those of neutral drugs (eg, theophylline). Drug release kinetics were governed by the ionization/erosion process with slight drug diffusion, observing no perfect straight line. A mathematical expression for drug release kinetics (erosion-controlled system) of TLDSTs is presented. In summary, a TLDST is a good design to obtain zero-order or nearly zero-order release kinetics for a wide range of drug solubilities