This is a Phase I, randomized, placebo-controlled, double-blind, multicenter, safety and tolerability study of ascending inhaled doses of IB-367 in adult patients with cystic fibrosis. Patients will be enrolled in groups of eight. In each group, patients will be randomized in a 3:1 fashion (6 active; 2 placebo) to receive IB-367 or placebo. All patients will be monitored as in-patients during the study. Each patient will participate in one treatment period only. This study will be conducted in two parts (A & B). During Part A, a group of 8 patients will be monitored in a single-blind, dose escalation phase for observation of any adverse events. Doses in this part of the study will vary by increasing administration of a single concentration of study drug. If IB-367 is well tolerated during the single-blind dose escalation, then subsequent cohorts of patients will receive single ascending doses administered in a double-blind manner (Part B). Patients in both parts of the study will be pre-treated with an inhaled bronchodilator prior to administering each dose. 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 procine 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. 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 182 mM, the level reported in cystic fibrosis airway surface fluid. We hypothesize that 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. The primary objectives are: 1) to determine the safety and tolerability of ascending doses of inhaled IB-367 in adult patients with cystic fibrosis 2) 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 FEV1 pre-and post-dose. The secondary objectives are: 1) to monitor for evidence of systemic absorption of IB-367 characterized by vasodilatory response or other toxicities.
Showing the most recent 10 out of 753 publications
