Efficacy of inhaled dry powder tobramycin (TOBI Podhaler) in P. aeruginosa infected patients with bronchiectasis - iBEST study

Background: This is the first study evaluating 3 different doses and 2 regimens of tobramycin inhalation powder (TIP) that reduces Pseudomonas aeruginosa (Pa) load in patients with bronchiectasis (BE). Methods: A phase II, double-blinded study including BE patients (≥18 years) with chronic Pa infection. Patients were randomised to Cohort A (3 capsules of TIP OD 84mg), B (5 capsules OD 140mg) or C (4 capsules BID 224mg). Within each Cohort, patients received either TIP continuously or cyclically (alternating 28 days of TIP and placebo [PBO]), or PBO for 16 weeks and were followed up for 8-weeks post-treatment. Results: Overall 107 patients were randomised to Cohort A (34), B (36) and C (37). The study achieved its primary objective in demonstrating significant Pa load reduction from baseline to Day 29 vs PBO in a dose dependent manner (Cohort A: 2.5 log colony forming unit [CFU]), B: 2.8 log CFU and C: 3.8 log CFU, all p≤0.001). Reduction in Pa load was higher in the pooled continuous treatment regimen than in the cyclical one. The proportion of patients with no Pa detected at two consecutive post-baseline visits was high with both continuous- and cyclical-TIP (52.3% and 50.0%, respectively). In the pooled PBO group, 1 (4.8%) patient had no Pa detected during the study. At study completion, about 1/3rd of the patients in the active arms remained Pa-free with TIP (continuous: 38.7% and cyclical: 36.4%). Conclusion: Continuous- and cyclical-TIP with all 3 doses were effective in reducing the Pa load in BE patients with chronic Pa infection. Also, trends in reduction of exacerbation episodes and use of anti-pseudomonal antibiotics were noted with TIP as compared to PBO.