The primary objectives of this study are to determine the safety and tolerability of ascending doses of inhaled IB-367 in adult patients with cystic fibrosis, and to determine whether potential bronchial reactivity to IB-367 is prevented by the prophylactic use of an inhaled bronchodilator in adult patients with cystic fibrosis as measured by change in FEV, pre- and post dose. Background: Persistent airway infections remain a major clinical problem for patients with cystic fibrosis. These infections are particularly difficult to treat because conventional antibiotics often do not achieve adequate delivery of drug to the site of infection and because the risk of inducing bacterial resistance often limits long-term therapies. IntraBiotics is developing a series of antimicrobial peptides based on protegrins, a family of naturally derived host-defense peptides initially isolated from porcine neutrophils. One such protegrin analog, IB-367, has been formulated as a solution for inhalation to be used in the treatment of respiratory infections, such as those in patients with cystic fibrosis. As a class, peptides of this group are broad spectrum, microbicidal agents that kill microorganisms rapidly by disrupting membrane integrity. IB-367 was selected as a drug candidate for the treatment of respiratory infections based on its ability to kill respiratory pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae. Aerosolized IB-367 directed to the site of infection in patients with cystic fibrosis may represent an effective alternative to current antimicrobial therapies. Recent research has shown that high salt concentrations in the airways of patients with cystic fibrosis causes local inhibition of an endogenous antimicrobial substance, and that this inhibition may be one of the factors predisposing patients with cystic fibrosis to pulmonary infections. The bactericidal activity of IB-367 is not significantly affected by sodium chloride concentrations up to 182mM, the level reported in cystic fibrosis airway surface fluid. The study will look at whether Inhaled IB-367 could replace the inactivated, naturally occurring antimicrobial host defense molecules in patients with cystic fibrosis and provide a substantial improvement in patient outcome.
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