PMID- 26830468 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20240325 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 16 DP - 2016 Feb 1 TI - A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase(R)) in adult subjects with well-controlled asthma. PG - 54 LID - 10.1186/s12879-016-1358-9 [doi] LID - 54 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 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT01113034 Trial Registration Date: April 27, 2010. FAU - Colombo, Rhonda E AU - Colombo RE AD - Division of Infectious Diseases, Georgia Regents University, Augusta, GA, USA. rcolombo@gru.edu. FAU - Fiorentino, Charles AU - Fiorentino C AD - Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. chuckfiorentino@gmail.com. FAU - Dodd, Lori E AU - Dodd LE AD - Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. doddl@niaid.nih.gov. FAU - Hunsberger, Sally AU - Hunsberger S AD - Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. sallyh@niaid.nih.gov. FAU - Haney, Carissa AU - Haney C AD - Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. carissahaney@aol.com. FAU - Barrett, Kevin AU - Barrett K AD - Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. kevin.barrett@nih.gov. FAU - Nabha, Linda AU - Nabha L AD - Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. linda.nabha@gmail.com. AD - Division of Infectious Diseases and Travel Medicine, Georgetown University Hospital, Washington, DC, USA. linda.nabha@gmail.com. FAU - Davey, Richard T Jr AU - Davey RT Jr AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. rdavey@niaid.nih.gov. FAU - Olivier, Kenneth N AU - Olivier KN AD - Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. kenneth.olivier@nih.gov. AD - Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA. kenneth.olivier@nih.gov. LA - eng SI - ClinicalTrials.gov/NCT01113034 GR - Intramural NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Intramural DEP - 20160201 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (Antiviral Agents) RN - 0 (Recombinant Fusion Proteins) RN - 227R1C272Q (oplunofusp) SB - IM MH - Administration, Inhalation MH - Adult MH - Antiviral Agents/*therapeutic use MH - Asthma/*drug therapy MH - Cross-Over Studies MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Recombinant Fusion Proteins/adverse effects/*therapeutic use MH - Sample Size MH - Young Adult PMC - PMC4736611 EDAT- 2016/02/03 06:00 MHDA- 2016/12/15 06:00 PMCR- 2016/02/01 CRDT- 2016/02/03 06:00 PHST- 2015/09/21 00:00 [received] PHST- 2016/01/18 00:00 [accepted] PHST- 2016/02/03 06:00 [entrez] PHST- 2016/02/03 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2016/02/01 00:00 [pmc-release] AID - 10.1186/s12879-016-1358-9 [pii] AID - 1358 [pii] AID - 10.1186/s12879-016-1358-9 [doi] PST - epublish SO - BMC Infect Dis. 2016 Feb 1;16:54. doi: 10.1186/s12879-016-1358-9.