Details

Autor(en) / Beteiligte

• Donaldson, Scott H
• Solomon, George M
• Zeitlin, Pamela L
• Flume, Patrick A
• Casey, Alicia
• McCoy, Karen
• Zemanick, Edith T
• Mandagere, Arun
• Troha, Janice M
• Shoemaker, Steven A
• Chmiel, James F
• Taylor-Cousar, Jennifer L

Titel

Pharmacokinetics and safety of cavosonstat (N91115) in healthy and cystic fibrosis adults homozygous for F 508 DEL - CFTR

Ist Teil von

• Journal of cystic fibrosis, 2017

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Abstract Background Cavosonstat (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. Methods A Phase I program evaluated pharmacokinetics, drug–drug interactions and safety of cavosonstat in healthy and cystic fibrosis (CF) subjects homozygous for F 508 del - CFTR . Exploratory outcomes included changes in sweat chloride in CF subjects. Results Cavosonstat 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 (− 4.1 mmol/L; P = 0.032) at day 28. Conclusions The favorable safety and clinical profile warrant further study of cavosonstat in CF. ClinicalTrials.gov Numbers: NCT02275936 , NCT02013388 , NCT02500667