CPX (ORAL, MULTIDOSE) IN ADULTS W/ MILD TO MODERATELY SEVERE CYSTIC F

囊性纤维化蛋白修复治疗是一种利用药物恢复CFTR突变分子功能的新方法。有可能激活驻留在囊性纤维化细胞中的CFTR突变体的概念得到了最近一些实验的支持。CPX（8-环戊基-1,3-二丙基黄嘌呤）是一类与CFTR直接相互作用的蛋白质修复药物。CPX是由美国国立卫生研究院（NIH）糖尿病、消化和肾脏疾病研究所（NIDDK）的Harvey Pollard医学博士和Kenneth Jacobson博士发现的。CPX是一种a1受体拮抗剂，以高特异性和亲和力结合DF508突变体CFTR第一个NBF结构域（NBF-1） 508位的核苷酸结合褶（NBF），激活囊性纤维化人气道细胞原代培养的向外氯离子电流。CPX是临床开发中唯一一种促进CFTR运输和刺激氯离子运输的囊性纤维化（CF）药物。本研究的主要目的是评估CPX多次递增口服剂量用于轻度至中重度囊性纤维化成人患者的安全性和有效性。疗效测定将使用鼻上皮跨膜电位差和汗液氯化物作为替代指标。次要目的是评估轻度和中度囊性纤维化成人患者多次口服递增剂量CPX的药代动力学。病人的住院才刚刚开始。

Cystic fibrosis protein-repair therapy is a new approach using drugs to restore function to mutant CFTR molecules. The concept that it might be possible to activate mutant CFTR resident in the cystic fibrosis cell has received support from a number of recent experiments. CPX (8-cyclopentyl-1,3-dipropylxanthine) is a new drug in the class of protein-repair therapeutics which may interact directly with the CFTR. CPX was discovered by Harvey Pollard, MD,PhD and Kenneth Jacobson, PhD, of the National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK) of the National Institutes of Health (NIH). CPX, an A1-receptor antagonist, binds with high specificity and affinity to the nucleotide-binding fold (NBF) at position 508 in the first NBF domain (NBF-1) of DF508 mutant CFTR, and activates outward chloride currents from primary cultures of cystic fibrosis human airway cells. CPX is the only cystic fibrosis (CF) drug in clinical development that promotes CFTR trafficking and stimulates chloride ion transport. The primary objective of this study is to evaluate the safety and efficacy of multiple ascending oral doses of CPX administered to adult patients with mild to moderately severe cystic fibrosis. Efficacy determination will use nasal epithelial transmembrane potential difference and sweat chloride as surrogate markers. The secondary objective is to evaluate the pharmacokinetics of multiple oral ascending doses of CPX administered to adult patients with mild and moderate cystic fibrosis. Patient accrural has just begun.