Abstract
IntroductionAerosolized tobramycin is a standard of care for chronic Pseudomonas aeruginosa (Pa) infection in patients with cystic fibrosis (CF). ObjectivesThe long-term safety and efficacy of intermittent (28-day on/off cycles) inhaled tobramycin nebulization solution 300mg/4ml (TNS4, Bramitob (R)/Bethkis (R)) was assessed over 56 weeks in CF patients aged 6 years having baseline 1sec forced expiratory volume (FEV1) 40-80% predicted.
MethodsPatients were initially randomized in an 8-week open-label trial (core phase) to compare TNS4 (N=159) and tobramycin 300mg/5ml (TNS5, TOBI (R)) (N=165). A subset of patients continued in a 48-week, single-arm extension receiving TNS4 only.
The primary endpoint of the core phase was to demonstrate the non-inferiority of TNS4 compared to TNS5 in terms of absolute change from baseline to week 4 in FEV1 % predicted. The assessment of long-term safety was the primary purpose of the extension phase.
Throughout all phases of the study, microbiological assessments, adverse events, and audiometry findings were also evaluated. ResultsIn the core phase (N=321), FEV1 (% predicted) increased from baseline (absolute change) following a single on-treatment cycle for both TNS4 (7.0%) and TNS5 (7.5%) and the non-inferiority between treatments was met [difference between treatments of -0.5 (95% CI: -2.6; 1.6)].
These improvements were maintained throughout the extension phase (N=209), ranging throughout the study between 5.1% (95% CI: 3.2; 6.9) and 8.1% (95% CI: 6.8; 9.4) compared to baseline. Pa sputum count reductions ranged between 0.6 (95% CI: 0.2; 0.9) to 2.3 (95% CI: 2.0; 2.6) log(10) CFU/g throughout the 56 weeks.
No remarkable safety issues were identified throughout both study phases, with similar percentages of patients reporting adverse events in the two treatment groups during the 8-week core phase [TNS4 (31.4%).