AN ASSESSMENT OF TIME TO ONSET OF BRONCHODILATION FOLLOWING TREATMENT WITH NEBULIZED ARFORMOTEROL IN PATIENTS WITH COPD

Abstract

SESSION TITLE: Wednesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Short and long-acting beta2-agonists are commonly utilized for the treatment of chronic obstructive pulmonary disease (COPD). Arformoterol tartrate (ARF; 15 μg twice daily [BID]) is a long-acting beta2-agonist (LABA) approved for the long-term maintenance treatment of bronchoconstriction in patients with COPD; ARF should not be used as rescue medication. ARF exhibits a rapid onset of action, producing significant bronchodilation and a long duration of effect. The time to onset of bronchodilation following treatment with nebulized ARF was assessed in COPD patients stratified by baseline forced expiratory volume in 1 second (FEV1) % predicted. METHODS: Data from two identical, 12-week, randomized Phase III trials (NCT00685841 and NCT00064402) evaluating improvement in airway function with ARF treatment in patients with COPD were pooled for analysis. Patients (n=1456; mean predicted FEV1=40.6% [standard deviation: 12.8]) received nebulized ARF 15 μg BID, 25 μg BID, or 50 μg once daily (QD), salmeterol 42 μg BID (using a metered dose inhaler), or placebo BID for 12 weeks. The time to onset was determined from serial spirometry assessments performed immediately and at 15 and 40 minutes, 1, 2, 3, 4, 5, 6, 8, 10, 12, 23, and 24 hours post-first dose. Time to onset of bronchodilation was defined as the time at which the linear interpolated value of FEV1 is equal to 12% change from baseline. The median time to onset, following administration of the first dose, was estimated using the Kaplan-Meier method. RESULTS: Across ARF treatment groups, time to onset of bronchodilation was quicker in the groups with the lowest baseline FEV1 % predicted. The median time to onset of bronchodilation for the approved ARF 15 μg BID dose, stratified by baseline FEV1 % predicted (<30, ≥30-<50, and ≥50), was 1.8, 3.6, and 42.2 minutes, respectively. The median time to onset was longer for placebo (122.1, 290.3, N/A) and salmeterol (14.6, 16.0, 43.7) groups by baseline FEV1 % predicted (<30, ≥30-<50, and ≥50, respectively) compared with ARF 15 μg BID. CONCLUSIONS: In this post-hoc analysis, median time to onset of bronchodilation in patients with COPD was shorter following treatment with nebulized ARF 15 μg BID than with placebo or salmeterol, regardless of baseline FEV1 % predicted. Notably, patients with COPD treated with nebulized ARF 15 μg BID demonstrated a rapid time to onset in patients with a baseline FEV1 % predicted <50%. CLINICAL IMPLICATIONS: Bronchodilators are essential in the management of COPD symptoms. These data highlight the rapid onset of bronchodilation observed with ARF 15 μg BID compared to placebo or salmeterol in all patients, independent of baseline disease severity. The observed differences between the clinically approved LABAs, ARF 15 ug BID and salmeterol 50 ug QD, may be due to dosing frequency, receptor uptake or mode of delivery. DISCLOSURES: Employee relationship with Sunovion Pharmaceuticals Please note: >$100000 Added 03/11/2019 by Thomas Goodin, source=Web Response, value=Salary Employee relationship with Sunovion Pharmaceuticals Please note: >$100000 Added 03/12/2019 by Ayca Ozol-Godfrey, source=Admin input, value=Salary Employee relationship with Sunovion Pharmaceuticals Please note: >$100000 Added 03/13/2019 by Barry Price, source=Web Response, value=Salary Employee relationship with Sunovion Pharmaceuticals Inc. Please note: >$100000 Added 03/14/2019 by Shahin Sanjar, source=Web Response, value=Salary Employee relationship with Sunovion Pharmaceuticals Inc. Please note: $20001 - $100000 Added 03/11/2019 by Sanjay Sharma, source=Web Response, value=Salary Removed 03/11/2019 by Sanjay Sharma, source=Web Response Employee relationship with Sunovion Pharmaceuticals, Inc. Please note: >$100000 Added 03/11/2019 by Sanjay Sharma, source=Web Response, value=Salary