title: A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma.
abstract: BACKGROUND
  Influenza virus (IFV) infection is associated with increased morbidity and mortality in people with underlying lung disease. Treatment options for IFV are currently limited and antiviral resistance is a growing concern. DAS181, an inhaled antiviral with a unique mechanism of action, has shown promise in early clinical trials involving generally healthy human subjects. This study was undertaken to assess the safety and tolerability of DAS181 in individuals with underlying reactive airway disease.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, crossover phase 1 study of DAS181-F02. Dry particle inhaler administration of 10 mg was done on 3 consecutive days in ten adult volunteers with well-controlled asthma. The primary outcome was the frequency of adverse events (AEs), grade 1 or higher that occurred during each study period.
  
  
  RESULTS
  There were 280 AEs among ten evaluable subjects (56.8 % active; 43.2 % placebo); 90.7 % were grade 1. No grade 3 or higher AEs occurred. A statistically significant association between exposure to DAS181 and experiencing any AE, a grade 1 AE, or a grade 2 AE was not detected. Overall, the majority of AEs were classified as possibly related (35.7 %), unlikely related (38.9 %), or unrelated (15.4 %) to study drug administration. However, there was a statistically significant association between exposure to DAS181 and experiencing a definitely or probably related AE. Respiratory effects, including dyspnea, dry cough, and chest discomfort related to respirations, accounted for all of the definitely related AEs and one of the most common probably related AEs.
  
  
  CONCLUSIONS
  DAS181 was safe in this small study of otherwise healthy subjects with well-controlled asthma. However, the generalizability of these results is limited by the small sample size and generally mild nature of the subjects' asthma at baseline. The increased association of respiratory events classified as probably or definitely related to DAS181 administration suggests caution may need to be employed when administering DAS181 to individuals with less stable reactive airway disease. Further investigation in a controlled setting of the safety and efficacy of DAS181 in a larger population of asthmatic subjects with varying disease activity is warranted.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01113034 Trial Registration Date: April 27, 2010.
authors.affiliation: Division of Infectious Diseases, Georgia Regents University, Augusta, GA, USA. rcolombo@gru.edu.
authors.forename: Rhonda E
authors.initials: RE
authors.lastname: Colombo
authors.affiliation: Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. chuckfiorentino@gmail.com.
authors.forename: Charles
authors.initials: C
authors.lastname: Fiorentino
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. doddl@niaid.nih.gov.
authors.forename: Lori E
authors.initials: LE
authors.lastname: Dodd
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. sallyh@niaid.nih.gov.
authors.forename: Sally
authors.initials: S
authors.lastname: Hunsberger
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. carissahaney@aol.com.
authors.forename: Carissa
authors.initials: C
authors.lastname: Haney
authors.affiliation: Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. kevin.barrett@nih.gov.
authors.forename: Kevin
authors.initials: K
authors.lastname: Barrett
authors.affiliation: Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. linda.nabha@gmail.com.|Division of Infectious Diseases and Travel Medicine, Georgetown University Hospital, Washington, DC, USA. linda.nabha@gmail.com.
authors.forename: Linda
authors.initials: L
authors.lastname: Nabha
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. rdavey@niaid.nih.gov.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. kenneth.olivier@nih.gov.|Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA. kenneth.olivier@nih.gov.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D018401:Sample Size; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; C525612:oplunofusp
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