TY - JOUR
T1 - A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma
AU - Colombo, Rhonda E.
AU - Fiorentino, Charles
AU - Dodd, Lori E.
AU - Hunsberger, Sally
AU - Haney, Carissa
AU - Barrett, Kevin
AU - Nabha, Linda
AU - Davey, Richard T.
AU - Olivier, Kenneth N.
N1 - Funding Information:
This study was approved by the National Institutes of Allergy and Infectious Diseases (NIAID) Institutional Review Board and was conducted in compliance with Good Clinical Practice Guidelines, the Declaration of Helsinki, and local regulatory requirements. The study was designed and conducted by NIAID investigators at the NIH and was funded by the Division of Intramural Research. The study drug, delivery device, and matched placebo were provided by the manufacturer of DAS181, Ansun Biopharma, Inc. The study agent and placebo were pre-randomized by the NIH Pharmaceutical Development Section (PDS) using a computer generated sequence. The randomization code was maintained by the PDS in a sealed envelope and stored in a locked cabinet with access available only for emergencies. Block randomization was done for the first four patients followed by review of safety data by an independent Safety Monitoring Committee. Stopping rules included any serious adverse event or Grade 4 adverse event deemed definitely or probably related to the study drug, anaphylactic or other life threatening reaction or acute drop in FEV1 to <50 % in response to study drug administration, or observed hemolysis associated or probably associated with the study drug.
Funding Information:
The study was funded in part by the Intramural Research Programs of the NIAID and NHLBI, NIH. Ansun Biopharma provided the DAS181-F02, placebo, and dry particle inhalers used in the study.
Publisher Copyright:
© 2016 Colombo et al.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - Antiviral
KW - Asthma
KW - DAS181
KW - Influenza
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UR - http://www.scopus.com/inward/citedby.url?scp=84957937643&partnerID=8YFLogxK
U2 - 10.1186/s12879-016-1358-9
DO - 10.1186/s12879-016-1358-9
M3 - Article
C2 - 26830468
AN - SCOPUS:84957937643
SN - 1471-2334
VL - 16
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
IS - 1
M1 - 54
ER -