117 Safety profile of levofloxacin inhalation solution from 3 controlled cystic fibrosis clinical trials

Objective To evaluate safety of levofloxacin inhalation solution (LIS) 240 mg BID in subjects with cystic fibrosis from 3 controlled trials. Methods Pooled disposition and treatment-emergent adverse events (AE) from subjects receiving LIS or placebo (PBO) in 2 double-blind, 28-day single-treatment cycle, controlled studies (MPEX-204 and –207) and LIS or tobramycin inhalation solution [TIS] 300 mg BID in 1 open-label, 28-day 3-cycle, controlled study (MPEX-209) were analysed. Data from MPEX-209 Ext. (28-day, 3-cycle, LIS only) were also analysed. Results The numbers of subjects (mean age) receiving ≥1 dose of study drug and included in the safety analyses were: 409 LIS (29 y), 146 PBO (29 y) and 90 TIS (29 y). Study discontinuations were: 6.8% LIS, 2.1% PBO and 7.8% TIS, primarily due to AEs (2.9% LIS; 2.1% PBO) or other (5.6% TIS). Early discontinuations of study drug (but not necessarily study participation) were: 13.9% LIS, 14.4% PBO and 15.6% TIS. Most common AEs in LIS group (LIS, PBO, TIS, respectively) were: cough (54.5%, 37.7%, 52.2%), disease progression (47.2%, 36.3%, 63.3%), sputum increase (43.5%, 29.5%, 44.4%), dysgeusia (31.3%, 0.7%, 0%), respiratory tract congestion (31.1%, 27.4%, 34.4%) and increased viscosity of bronchial secretion (23.7%, 14.4%, 31.1%). Possible/probable treatment-related AEs (>1) occurred in 48.2% LIS (mainly dysgeusia), 18.5% PBO and 15.6% TIS subjects. Disease progression was the most common serious AE (10.8% LIS, 8.9% PBO, 21.1% TIS); no deaths occurred. No new safety signals were noted in the MPEX-209 extension. Conclusion LIS was safe and generally well-tolerated, with dysgeusia the only distinguishing AE compared with TIS.