دورية أكاديمية

Safety, Pharmacokinetics, and Antifibrotic Activity of CC‐90001 (BMS‐986360), a c‐Jun N‐Terminal Kinase Inhibitor, in Pulmonary Fibrosis.

التفاصيل البيبلوغرافية
العنوان: Safety, Pharmacokinetics, and Antifibrotic Activity of CC‐90001 (BMS‐986360), a c‐Jun N‐Terminal Kinase Inhibitor, in Pulmonary Fibrosis.
المؤلفون: Horan, Gerald, Ye, Ying, Adams, Mary, Parton, Anastasia, Cedzik, Dorota, Tang, Shaojun, Brown, Elizabeth A., Liu, Liangang, Nissel, Jim, Carayannopoulos, Leonidas N., Gaudy, Allison, Schafer, Peter, Palmisano, Maria, Ramirez‐Valle, Francisco
المصدر: Clinical Pharmacology in Drug Development; Aug2023, Vol. 12 Issue 8, p779-789, 11p
مصطلحات موضوعية: PULMONARY fibrosis, IDIOPATHIC pulmonary fibrosis, KINASE inhibitors, VITAL capacity (Respiration), TRANSFORMING growth factors-beta, PHARMACOKINETICS
مستخلص: Approved treatments for idiopathic pulmonary fibrosis have tolerability concerns and limited efficacy. CC‐90001, a c‐Jun N‐terminal kinase inhibitor, is under investigation as a therapy for fibrotic diseases. A Phase 1b safety, pharmacokinetics, and pharmacodynamics study of oral CC‐90001 (100, 200, or 400 mg) administered once daily for 12 weeks was conducted in patients with pulmonary fibrosis (NCT02510937). Sixteen patients with a mean age of 68 years were studied. The most common treatment‐emergent adverse events were nausea and headache; all events were of mild or moderate intensity. Pharmacokinetic profiles were similar between the patients in this trial and healthy adults in previous studies. Forced vital capacity increased in the 200‐ and 400‐mg cohorts from baseline to Week 12, and dose‐dependent reductions in fibrosis biomarkers were observed. Antifibrotic activity of CC‐90001 was also evaluated in vitro in transforming growth factor beta 1 (TGF‐β1)–stimulated cells. CC‐90001 reduced in vitro profibrotic gene expression in both lung epithelial cells and fibroblasts, supporting a potential direct antifibrotic action of c‐Jun N‐terminal kinase inhibition in either or both cell types. Overall, CC‐90001 was generally safe and well tolerated, and treatment was associated with forced vital capacity improvement and reductions in profibrotic biomarkers. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:2160763X
DOI:10.1002/cpdd.1294