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.
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