title: Long-term safety of tobramycin inhalation powder in patients with cystic fibrosis: phase IV (ETOILES) study.
abstract: Long-term treatment with inhaled antibiotics is recommended for chronic Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients. The ETOILES study (Clinicaltrials.gov identifier: NCT01519661) evaluated the safety of tobramycin inhalation powder (TIP) for 1 year.
  
  
  
  This single-arm, open-label, multicenter, phase IV trial, enrolled CF patients aged ≥6 years, with baseline FEV1≥25%-≤75% predicted and Pa infection, and assessed the safety of TIP over six cycles in terms of the incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs). Secondary endpoints included presence of airway reactivity, relative change in FEV1% predicted, and change in sputum Pa density (log10colony forming units/g sputum).
  
  
  
  A total of 157 patients were enrolled, and 96 patients (61.1%) completed the study. The most commonly reported AE was infective pulmonary exacerbation of CF (55.4%). Cough was reported as an AE in 23.6% of patients; a majority were mild or moderate and two were severe (1.3%). SAEs were reported by 31.2% of patients. No deaths were reported during the study. There were no clinically meaningful changes reported in airway reactivity. Most frequently reported post-inhalation event was cough at all time points; however, it was of short duration (<4 minutes) and decreased over the course of the study, possibly due to patients becoming more experienced with the administration of TIP. The post-inhalation events resolved without intervention in most cases. FEV1% predicted remained stable from Cycles 1 to 4 and tended to decrease thereafter, although it was not statistically significant (change from baseline to study end mean [SD] = -1.9% [14.55]; P = 0.199).
  
  
  
  This was one of the largest studies with long-term TIP exposure. The majority of patients enrolled were adults with more advanced CF lung disease than those in previous TIP studies. No new emerging safety signals were seen and efficacy was sustained during the year.
authors.affiliation: a Department of Pneumology , Ruhrlandklinik, West German Lung Centre, University Hospital Essen , Essen , Germany.|b Christiane Herzog Center Ruhr , Essen/Bochum , Germany.
authors.forename: Urte
authors.initials: U
authors.lastname: Sommerwerck
authors.affiliation: c Department of Pediatrics , Medical University of South Carolina, Pediatric Pulmonology and Sleep Medicine , Charleston , SC , USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Virella-Lowell
authors.affiliation: d Novartis Pharma AG , Basel , Switzerland.
authors.forename: Gerhild
authors.initials: G
authors.lastname: Angyalosi
authors.affiliation: e Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Viegas
authors.affiliation: e Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA.
authors.forename: Weihua
authors.initials: W
authors.lastname: Cao
authors.affiliation: e Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Debonnett
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D003371:Cough / Q000139:chemically induced; D003550:Cystic Fibrosis / Q000150:complications* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D011208:Powders; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D014031:Tobramycin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D011208:Powders; D014031:Tobramycin
keywords: Cystic fibrosis; Dry powder inhaler (DPI); Pseudomonas aeruginosa; Safety; Tobramycin