Sunovion

About: Sunovion is a company organization based out in London, United Kingdom. It is known for research contribution in the topics: Lurasidone & Placebo. The organization has 572 authors who have published 1022 publications receiving 18488 citations. The organization is also known as: Sunovion Pharmaceuticals, Inc..

Effect of background long-acting beta 2 -agonist therapy on the efficacy and safety of a novel, nebulized glycopyrrolate in subjects with moderate-to-very-severe COPD

Abstract: Background Phase III studies demonstrated efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY) in subjects with COPD Secondary analyses were performed to examine the effect of background long-acting beta2-agonist (LABA) use on the efficacy and safety of nebulized GLY Methods In two 12-week placebo-controlled studies (GOLDEN 3 and GOLDEN 4) and one 48-week, open-label active-controlled study (GOLDEN 5), a total of 2,379 subjects were stratified by background LABA use (LABA-yes: n=861; LABA-no: n=1,518) and randomized to placebo vs GLY 25 or 50 µg twice daily, or GLY 50 µg twice daily vs tiotropium (TIO) 18 µg once daily Lung function, patient-reported outcomes, exacerbations, and safety were assessed Results Compared with placebo, pooled data from the 12-week studies showed significant improvements from baseline with GLY 25 and 50 µg across LABA subgroups in trough FEV1 (LABA-yes: 0101 and 0110 L; LABA-no: 0092 and 0101 L, respectively; P<0001) and St George's Respiratory Questionnaire total score (SGRQ; LABA-yes: -2957 and -3888; LABA-no: -3301 and -2073, respectively; P<005) Incidence of treatment-emergent adverse events (TEAEs) was similar in LABA subgroups, and lower in GLY 25 µg vs placebo In the 48-week active-controlled study, GLY and TIO both showed improvement from baseline across LABA subgroups in FEV1 (LABA-yes: 0106 and 0092 L; LABA-no: 0096 and 0096 L, respectively) and in SGRQ total score (LABA-yes: -5190 and -3094; LABA-no: -4368 and -4821, respectively) Incidence of TEAEs was similar between GLY and TIO, and across LABA subgroups Exacerbation rates were similar across treatments and LABA subgroups, and cardiovascular events of special interest were more frequent in the LABA-no subgroup Nebulized GLY, combined with LABA, did not generate any additional safety signals Conclusion Nebulized GLY demonstrated efficacy and was well tolerated up to 48 weeks in subjects with COPD with/without background LABA

Compounds useful in enzymatic resolution systems and their preparation

Abstract: This invention relates to novel compositions of matter which are esters with enhanced water solubility, for use in aqueous enzymatic resolution reactions of racemic mixtures of these esters for producing the separate chiral isomers of the racemic mixture. The invention also relates to novel methods for preparing these esters. The importance of the production of the separate chiral isomers of the racemic mixtures resides in the isolation of the isomers which frequently have different biological activities. Of particular significance regarding the water soluble esters of this invention is that they are derivatized with groups which enhance their aqueous solubility and their reactivity with enzymatic resolving methods which are mediated in an aqueous environment. In addition, the importance of these compounds resides in their being useful in novel methods for facilitating the enzymatic resolution reactions of racemic mixtures of esters, which are derivatized with groups which enhance the esters' aqueous solubility, in 1) a homogeneous aqueous reaction system where an extractive phase is not present, 2) a multiphase dispersion extractive reaction where an extractive phase is present, and 3) an extractive membrane reactor where the enzyme is placed alternatively either (a) in the aqueous phase, (b) in association with the membrane, or (c) in the aqueous phase and in association with the membrane, wherein the aqueous ester phase is contacted with one side of the membrane, and where an organic extractive phase is contacted with the other side of the membrane, wherein the extractive phase serves to remove the resolving reaction product.

Identification of critical amino acid residues for human iNOS functional activity.

Abstract: Nitric oxide (NO) is a short-lived signaling molecule that mediates a variety of biological functions, including vascular homeostasis, neurotransmission, antimicrobial defense and antitumor activities. Three known NOS isoforms (eNOS, nNOS and iNOS) have been cloned and sequenced. Here, we show that upon expression in Escherichia coli using a novel expression vector, an iNOS sequence containing three mutations (A805D, F831S and L832P) within the iNOS reductase domain produced very little functionally active iNOS protein compared to the wild type (wt) iNOS. Each of these point mutations also was individually constructed into the wt iNOS sequence. The activity of the iNOS protein containing the A805D mutation was comparable to wt, while a drastic reduction in iNOS activity was observed for the F831S and L832P mutants. A comparison of the molecular models of the reductase domain of the wt and mutant iNOS revealed a reduced core packing density for the F831S and L832P mutations compared to wt. In addition, the modeling also suggests altered hydrogen bonding, van der Waals and hydrophobic interactions of these mutants.

Dual nav1.2/5ht2a inhibitors for treating cns disorders

Abstract: Compounds of formula I: I are disclosed, as are pharmaceutical compositions containing such compounds. Methods of treating neurological or psychiatric disorders in a patient in need are also disclosed. Such disorders include depression, bipolar disorder, pain, schizophrenia, obsessive compulsive disorder, addiction, social disorder, attention deficit hyperactivity disorder, an anxiety disorder, autism, a cognitive impairment, or a neuropsychiatric symptom such as apathy, depression, anxiety, psychosis, aggression, agitation, impulse control disorders, and sleep disorders in neurological disorders such as Alzheimer's and Parkinson's diseases.

Regulatory Definitions and Good Pharmacovigilance Practices in Social Media: Challenges and Recommendations.

Abstract: Social media presents new challenges to the biopharmaceutical industry for conducting pharmacovigilance activities. The authors reviewed worldwide regulatory guidance documents related to monitoring of adverse events posted on social media sites and identified gaps in current regulatory definitions for pharmacovigilance. Points to consider for addressing these gaps are made to offer standards for industry consideration and a potential framework for guidance from global health authorities.