کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5724525 | 1411499 | 2017 | 9 صفحه PDF | دانلود رایگان |
BackgroundCavosonstat (N91115), an orally bioavailable inhibitor of S-nitrosoglutathione reductase, promotes cystic fibrosis transmembrane conductance regulator (CFTR) maturation and plasma membrane stability, with a mechanism of action complementary to CFTR correctors and potentiators.MethodsA Phase I program evaluated pharmacokinetics, drug-drug interactions and safety of cavosonstat in healthy and cystic fibrosis (CF) subjects homozygous for F508del-CFTR. Exploratory outcomes included changes in sweat chloride in CF subjects.ResultsCavosonstat was rapidly absorbed and demonstrated linear and predictable pharmacokinetics. Exposure was unaffected by a high-fat meal or rifampin-mediated effects on drug metabolism and transport. Cavosonstat was well tolerated, with no dose-limiting toxicities or significant safety findings. At the highest dose, significant reductions from baseline in sweat chloride were observed (â 4.1 mmol/L; P = 0.032) at day 28.ConclusionsThe favorable safety and clinical profile warrant further study of cavosonstat in CF.ClinicalTrials.gov Numbers: NCT02275936, NCT02013388, NCT02500667
Journal: Journal of Cystic Fibrosis - Volume 16, Issue 3, May 2017, Pages 371-379