PHARMACOKINETICS OF 552-02 FOLLOWING 14 DAYS OF DOSING BY INHALATION IN PTS W/CF

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This clinical study is a multiple site, double blind, placebo-controlled Phase 2 study in patients with cystic fibrosis. The primary objective of this study is to evaluate the safety and tolerability of 552-02, a specific inhibitor of the epithelial sodium channel, after daily aerosolized administration for fourteen days in patients with cystic fibrosis. The secondary objective is to evaluate the plasma pharmacokinetics of 552-02 after daily aerosolized administration for fourteen days in patients with cystic fibrosis. Up to 40 patients with cystic fibrosis will participate in the study. Patients will be randomized to receive either a 1.3 milligram dose of 552-02 or placebo (0.12 % sodium chloride) in a 1:1 ratio. Patients will self-administer drug or placebo once daily for fourteen days by a nebulizer via the mouth. Instructions for nebulization can be found in the Study Reference Manual. Patients who prematurely discontinue may be replaced. A screening visit will be performed (Day -28 to Day -1, Visit 1). Eligible patients who meet the criteria for enrollment will be randomized to receive 552-02 or placebo daily for fourteen days (Day 1 through Day 14). All patients will visit the clinic on study Day 1 (Visit 2), Day 7 (Visit 3) and Day 14 (Visit 4). Subjects will also have a lab only visit at Day 3 or Day 4 of treatment for clinical chemistry assessment to verify that the potassium levels are not trending upward between Day 1 and Day 7. Procedures and assessments at clinic visits include dose administration, safety assessments (physical examination, spirometry, pulse oximetry, vital signs, ECGs, hematology, clinical chemistry, plasma panel, urinalysis), and assessment for adverse events. In addition, blood samples for pharmacokinetic analysis will be taken on Day 14 for patients assigned to the PK subgroup. Patients will receive study drug or placebo in the clinic on Days 1, 7 and 14. All patients will be instructed to self-administer treatment on study Days 2-6 and Days 8-13. Patients will be contacted by telephone on Day 1 and Day 7 to assess for adverse events. Patients will also be contacted by telephone three days following administration of the last dose of 552-02 or placebo to assess for adverse events. Treatment will be suspended on an individual patient basis if administration of 552-02 or placebo for fourteen days is associated with the development of dose limiting toxicity. A detailed Schedule of Time and Events is presented in Table 1, which includes a complete listing of all scheduled assessments by study day.