ars 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
Pyrexia 15.6 12.4
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain 4.5 4.8
Skin and subcutaneous tissue disorders
Rash 2.3 2.4
1This includes adverse events of pulmonary or cystic fibrosis exacerbations
Adverse drug reactions that occurred in <2% of patients treated with TOBI Podhaler in Study 1 were: bronchospasm (TOBI Podhaler 1.6%, TOBI 0.5%); deafness including deafness unilateral (reported as mild to moderate hearing loss or increased hearing loss) (TOBI Podhaler 1.0%, TOBI 0.5%); and tinnitus (TOBI Podhaler 1.9%, TOBI 2.4%).
Discontinuations in Study 1 were higher in the TOBI Podhaler arm compared to TOBI (27% TOBI Podhaler vs 18% TOBI). This was driven primarily by discontinuations due to adverse events (14% TOBI Podhaler vs 8% TOBI). Higher rates of discontinuation were seen in subjects ≥ 20 years old and those with baseline FEV1 % predicted < 50%.
Respiratory related hospitalizations occurred in 24% of the patients in the TOBI Podhaler arm and 22% of the patients in the TOBI arm. There was an increased new usage of antipseudomonal medication in the TOBI Podhal
