Introduction: New inhaled antimicrobials for CF patients are needed due to increased resistance, decreased efficacy and poor compliance/tolerability. This study assessed the efficacy and safety of MP-376, a novel levofloxacin formulation for inhalation, in CF patients with extensive previous use of inhaled antibiotics. Methods: Randomized, double-blind, placebo controlled trial of 3 dose groups of MP-376 (120mg QD, 240mg QD, 240mg BID) vs. placebo for 28 days, delivered by a customized investigational PARI eFlow nebulizer. Inclusion criteria: age (greater-than or equal to)16 years, chronic PA airways infection, FEV1 between 25-85% predicted, and (greater-than or equal to)3 courses of inhaled antibiotics over the past 12 months. Results: 151 patients enrolled with mean baseline characteristics of age 29 years, FEV1 52% of predicted, and 4.8 courses of inhaled antibiotics over last 12 months. Concomitant respiratory medications included dornase-alpha (78%), azithromycin (74%), and hypertonic saline (46%). Improvement in lung function was observed in all dose groups, the largest seen with 240 mg BID. At Day 28, improvements over placebo in this group were change in FEV1 8.6% (p = 0.0026), relative change in percent predicted FEV1 10.9% (p = 0.0008), change in FVC 5.7% (p = 0.0221) and change in FEF 25-75 22.3% (p < 0.0001). Statistically significant results were also observed in all MP-376 dose groups for sputum PA density reduction and in time to need for inhaled and/or systemic anti-PA antimicrobials. Conclusion: Nebulized MP-376 (Aeroquin) demonstrated statistically and clinically significant improvement in lung function in this heavily-treated CF patient population with PA lung infection. Phase 3 studies are planned.
Flume, P., Geller, D. E., Sindel, L., Staab, D., Fischer, R., Riethmüller, J., … Conrad, D. (2010). Effects of inhaled MP-376 (aeroquin, levofloxacin inhalation solution) on lung function in stable cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa (PA) lung infection. Journal of Cystic Fibrosis, 9, S23. https://doi.org/10.1016/s1569-1993(10)60087-2