Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients
| Autor: | Sally E. Wenzel, Nan Zhang, Edward Kerwin, Mark C. Liu, William W. Busse, Eli O. Meltzer, Yun Chon, Alison L. Budelsky, Shao Lee Lin, Joseph Lin |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.drug_class Receptors Prostaglandin Immunology Fevipiprant Placebo Anti-asthmatic Agent law.invention Double-Blind Method Randomized controlled trial Adrenal Cortex Hormones law Internal medicine medicine Humans Immunology and Allergy Anti-Asthmatic Agents Receptors Immunologic Adverse effect Phenylacetates Asthma Sulfonamides Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Respiratory Function Tests Asthma Control Questionnaire Anesthesia Corticosteroid Drug Therapy Combination Female business |
| Zdroj: | Journal of Allergy and Clinical Immunology. 131:339-345 |
| ISSN: | 0091-6749 |
| DOI: | 10.1016/j.jaci.2012.10.013 |
| Popis: | Background The D-prostanoid receptor and the chemoattractant receptor homologous molecule expressed on T H 2 cells (CRTH2) are implicated in asthma pathogenesis. AMG 853 is a potent, selective, orally bioavailable, small-molecule dual antagonist of human D-prostanoid and CRTH2. Objective We sought to determine the efficacy and safety of AMG 853 compared with placebo in patients with inadequately controlled asthma. Methods Adults with moderate-to-severe asthma were randomized to placebo; 5, 25, or 100 mg of oral AMG 853 twice daily; or 200 mg of AMG 853 once daily for 12 weeks. All patients continued their inhaled corticosteroids. Long-acting β-agonists were not allowed during the treatment period. Allowed concomitant medications included short-acting β-agonists and a systemic corticosteroid burst for asthma exacerbation. The primary end point was change in total Asthma Control Questionnaire score from baseline to week 12. Secondary and exploratory end points included FEV 1 , symptom scores, rescue short-acting β-agonist use, and exacerbations. Results Among treated patients, no effect over placebo (n = 79) was observed in mean changes in Asthma Control Questionnaire scores at 12 weeks (placebo, −0.492; range for AMG 853 groups [n = 317], −0.444 to −0.555). No significant differences between the active and placebo groups were observed for secondary end points. The most commonly reported adverse events were asthma, upper respiratory tract infection, and headache; 9 patients experienced serious adverse events, all of which were deemed unrelated to study treatment by the investigator. Conclusion AMG 853 as an add-on to inhaled corticosteroid therapy demonstrated no associated risks but was not effective at improving asthma symptoms or lung function in patients with inadequately controlled moderate-to-severe asthma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect