title: A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients.
abstract: For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF.
  
  
  
  To compare the safety and efficacy of a 28-day course of treatment with LIS 240mg or placebo BID in persons ≥12years old with CF and chronic P. aeruginosa infection.
  
  
  
  A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28days in CF patients ≥12years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported quality of life were among secondary endpoints.
  
  
  
  Baseline demographics for 330 subjects (LIS=220) were similar although significantly more patients randomized to LIS had experienced multiple exacerbations in the year prior to study entry. There was no statistically significant difference in protocol-defined pulmonary exacerbations between treatment arms. Relative change in FEV1% predicted from baseline was significantly greater for patients randomized to LIS compared to those randomized to placebo (mean difference 1.31%, p=0.01 [95% CI 0.27, 2.34%]). LIS was well-tolerated, with dysguesia the most frequent adverse event.
  
  
  
  LIS did not demonstrate a difference in time to next exacerbation when compared to placebo. Reasons for this result are discussed but may be due to an imbalance in the frequency of prior pulmonary exacerbations between the two groups. An improvement in FEV1 (% predicted) at 28days was observed and LIS was well tolerated. LIS is safe and has a potential role in the management of CF patients with chronic P. aeruginosa.
authors: Departments of Medicine and Pediatrics, Medical University of South Carolina, Charleston, SC, USA. Electronic address: flumepa@musc.edu.
authors: Patrick A
authors: PA
authors: Flume
authors: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Donald R
authors: DR
authors: VanDevanter
authors: The Medicines Company, San Diego, CA, USA.
authors: Elizabeth E
authors: EE
authors: Morgan
authors: The Medicines Company, San Diego, CA, USA.
authors: Michael N
authors: MN
authors: Dudley
authors: The Medicines Company, San Diego, CA, USA.
authors: Jeffery S
authors: JS
authors: Loutit
authors: The Prince Charles Hospital and QIMR Berghofer Medical Research Institute, Queensland, Brisbane, Australia.
authors: Scott C
authors: SC
authors: Bell
authors: Department of Pediatrics, Hadassah Medical Center, Jerusalem, Israel.
authors: Eitan
authors: E
authors: Kerem
authors: Pneumologische Praxis München-Pasing, Munich, Germany.
authors: Rainald
authors: R
authors: Fischer
authors: Division of Child Health, Obstetrics & Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK.
authors: Alan R
authors: AR
authors: Smyth
authors: The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors: Shawn D
authors: SD
authors: Aaron
authors: Department of Medicine, University of California, San Diego, CA, USA.
authors: Douglas
authors: D
authors: Conrad
authors: Florida State University College of Medicine, Orlando, FL, USA.
authors: David E
authors: DE
authors: Geller
authors: Centre for Infection and Immunity, Queens University Belfast, Belfast BT9 7AE, UK.
authors: J Stuart
authors: JS
authors: Elborn
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology / Q000523:psychology; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D064704:Levofloxacin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D011788:Quality of Life; D063189:Symptom Assessment; D000067251:Symptom Flare Up; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin
keywords: Aerosol; Antibiotics; Cystic fibrosis; Fluoroquinolone; Pseudomonas