A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma

Rhonda E. Colombo, Charles Fiorentino, Lori E. Dodd, Sally Hunsberger, Carissa Haney, Kevin Barrett, Linda Nabha, Richard T. Davey, Kenneth N. Olivier

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 10mg 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.

Original languageEnglish (US)
Article number54
JournalBMC Infectious Diseases
Volume16
Issue number1
DOIs
StatePublished - Feb 1 2016

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Cross-Over Studies
Asthma
Placebos
Orthomyxoviridae
Antiviral Agents
Healthy Volunteers
Safety
DAS181
Nebulizers and Vaporizers
Virus Diseases
Cough
Dyspnea
Sample Size
Lung Diseases
Volunteers
Respiration
Thorax
Clinical Trials
Morbidity
Mortality

Keywords

  • Antiviral
  • Asthma
  • DAS181
  • Influenza

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma. / Colombo, Rhonda E.; Fiorentino, Charles; Dodd, Lori E.; Hunsberger, Sally; Haney, Carissa; Barrett, Kevin; Nabha, Linda; Davey, Richard T.; Olivier, Kenneth N.

In: BMC Infectious Diseases, Vol. 16, No. 1, 54, 01.02.2016.

Research output: Contribution to journalArticle

Colombo, RE, Fiorentino, C, Dodd, LE, Hunsberger, S, Haney, C, Barrett, K, Nabha, L, Davey, RT & Olivier, KN 2016, 'A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma', BMC Infectious Diseases, vol. 16, no. 1, 54. https://doi.org/10.1186/s12879-016-1358-9
Colombo, Rhonda E. ; Fiorentino, Charles ; Dodd, Lori E. ; Hunsberger, Sally ; Haney, Carissa ; Barrett, Kevin ; Nabha, Linda ; Davey, Richard T. ; Olivier, Kenneth N. / A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma. In: BMC Infectious Diseases. 2016 ; Vol. 16, No. 1.
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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 10mg 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.",
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