CPX (8‐cyclopentyl‐1,3‐dipropylxanthine) is a novel compound currently under development as a potential treatment for cystic fibrosis (CF). The drug has been shown to increase chloride efflux and CFTR trafficking in vitro in CF airway cells. This phase I multicenter, single‐dose, placebo‐controlled trial was performed at four institutions. Thirty‐seven subjects homozygous for the ΔF₅₀₈ allele were studied in an escalating dose protocol of seven single‐dose cohorts (1, 3, 10, 30, 100, 300, and 1,000 mg) to evaluate the safety, pharmacokinetics, and efficacy of CPX. Efficacy was determined using nasal transepithelial potential difference and sweat chloride measurements prior to dosing and at 1, 2, and 4 hr postdose.

The incidence of adverse events in the treatment group was similar to that with placebo, indicating safety of the single doses studied. One serious adverse event (an acute pulmonary exacerbation) occurred 13 days after dosing, and was not considered related to the study drug. The maximal plasma CPX concentration and total amount of CPX absorbed appeared to be linearly related to dose, but was highly variable throughout the dose range studied, suggesting inconsistent absorption. There was no apparent effect of single‐dose administration on either nasal transepithelial potential difference or sweat chloride measurements.

The positive safety and pharmacokinetic findings of this study support continued development of CPX as a potential therapeutic for CF. Pediatr Pulmonol. 2002; 33:90–98. © 2002 Wiley‐Liss, Inc.