TOBI Podhaler has been eva luated for safety in 425 cystic fibrosis patients exposed to at least one dose of TOBI Podhaler, including 273 patients who were exposed across three cycles (6 months) of treatment. Each cycle consisted of 28 days on-treatment (with 112 mg administered twice daily) and 28 days off-treatment. Patients with serum creatinine ≥ 2 mg/dL and blood urea nitrogen (BUN) ≥ 40 mg/dL were excluded from clinical studies. There were 218 males and 207 females in this population, and reflecting the cystic fibrosis population in the U.S., the vast majority of patients were Caucasian. There were 221 patients ≥ 20 years old, 121 patients ≥ 13 to < 20 years old, and 83 patients ≥ 6 to < 13 years old. There were 239 patients with screening FEV1 % predicted ≥ 50%, 156 patients with screening FEV1 % predicted < 50%, and 30 patients with missing FEV1 % predicted.
The primary safety population reflects patients from Study 1, an open-label study comparing TOBI Podhaler with TOBI (tobramycin inhalation solution, USP) over three cycles of 4 weeks on treatment followed by 4 weeks off treatment. Randomization, in a planned 3:2 ratio, resulted in 308 patients treated with TOBI Podhaler and 209 patients treated with TOBI. For both the TOBI Podhaler and TOBI groups, mean exposure to medication for each cycle was 28-29 days. The mean age for both arms was between 25 and 26 years old. The mean baseline FEV1 % predicted for both arms was 53%.

Table 1 displays adverse drug reactions reported by at least 2% of TOBI Podhaler patients in Study 1, inclusive of all cycles (on and off treatment). Adverse drug reactions are listed according to MedDRA system organ class and sorted within system organ class group in descending order of frequency.

Table 1: Adverse reactions reported in Study 1 (occurring in ≥2% of TOBI Podhaler patients) Primary System Organ Class
Preferred Term TOBI Podhaler
N=308
% TOBI
N=209
%
Respiratory, thoracic, and mediastinal disorders    
Cough 48.4 31.1
Lung disorder1 33.8 30.1
Productive cough 18.2 19.6
Dyspnea 15.6 12.4
Oropharyngeal pain 14.0 10.5
Dysphonia 13.6 3.8
Hemoptysis 13.0 12.4
Nasal congestion 8.1 7.2
Rales 7.1 6.2
Wheezing 6.8 6.2
Chest discomfort 6.5 2.9
Throat irritation 4.5 1.9
Gastrointestinal disorders    
Nausea 7.5 9.6
Vomiting 6.2 5.7
Diarrhea 4.2 1.9
Dysgeusia 3.9 0.5
Infections and infestations    
Upper respiratory tract infection 6.8 8.6
Investigations    
Pulmonary function test decreased 6.8 8.1
Forced expiratory volume decreased 3.9 1.0
Blood glucose increased 2.9 0.5
Vascular disorders    
Epistaxis 2.6 1.9
Nervous system disorders    
Headache 11.4 12.0
General disorders and administration site conditions  &nb