Multicenter, randomized, double-blind, placebo-controlled, dose-escalation study. Following a screening period, patients will begin a treatment period during which they will be entered into one of six cohors. Cystic fibrosis (CF) is a common inherited life-threatening disease affecting approximately 20,000 individuals in the U.S. and 50,000 worldwide. CF is inherited in a classic Mendelian autosomal recessive pattern with an estimated incidence of 1:2500 Caucasian births. The pharmacokinetic (PK) and pharmacodynamic (PD) attributes of DMP 777 as shown in animals may be beneficial in the treatment of CF lung disease. DMP 777 is a potent inhibitor of polymorphonuclear leukocytes elastase located both within he azurophilic granules of viable cells and extracellularly following release at tissue sites of activation.
Specific Aims : 1) To evaluate safety and tolerability of multiple oral doses of DMP 777 administered at six different dose levels 2) To determine PK and PD characteristics of multiple oral doses of DMP 777 administered at six different dose levels and/or regimens 3) To define DMP 777 dosage levels necessary to achieve sustained high-level systemic neutrophil elastase inhibition as determined by measurements of circulating PMN-lysate AAPVase inhibition and whole blood urea fragment formation obtained at both peak and trough concentrations of parent compound, in a selectively defined cohort of patients with cystic fibrosis following oral administration of DMP 777 for 9 days duration (twice or thrice daily).
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