Revefenacin Area Under the Curve Spirometry in Patients with Moderate to Very Severe COPD

William Blake LeMaster,1 Corey J Witenko,2 Melinda K Lacy,2 Ann W Olmsted,2 Edmund J Moran,2 Donald A Mahler3,4 1Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; 2Theravance Biopharma US, Inc, South San Francisco, CA, USA; 3Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 4Respiratory Services, Valley Regional Hospital, Claremont, NH, USACorrespondence: Edmund J Moran, Theravance Biopharma US, Inc, 901 Gateway Boulevard, South San Francisco, CA, 94080, USA, Tel +1 650 892 9229, Email [email protected]: Several lung function endpoints are utilized in clinical trials of inhaled bronchodilators for chronic obstructive pulmonary disease (COPD). Trough forced expiratory volume in 1 second (FEV1) is a commonly reported endpoint in COPD trials and can be complemented by area under the FEV1 vs time curve (FEV1 AUC), which provides information on duration and consistency of bronchodilation over a dosing interval. Revefenacin, a once-daily bronchodilator, significantly improved lung function in patients with COPD when measured by trough FEV1 in two replicate Phase 3 trials. Here, we report an FEV1 AUC substudy using data from these trials.Patients and Methods: This post hoc analysis examined substudy data from 12-week replicate Phase 3 trials (NCT02459080/NCT02512510); patients with moderate to very severe COPD were randomized 1:1 to revefenacin 175 μg or placebo once daily. The substudy patients had FEV1 AUC0– 2h assessed on Day 1, and those who continued to Day 84 also underwent 24-hour serial spirometry postdose where FEV1 AUC0– 2h, AUC0– 12h, AUC12-24h, and AUC0– 24h were evaluated.Results: Fifty and 47 patients who received revefenacin and placebo underwent 24-hour serial spirometry; most baseline characteristics were aligned between groups. At Day 84 postdose, revefenacin demonstrated sustained improvements in bronchodilation over 24 hours; differences in least squares mean vs placebo were 282, 220, 205, and 212 mL for FEV1 AUC0– 2h, AUC0– 12h, AUC12– 24h, and AUC0– 24h (all P < 0.001), respectively.Conclusion: This substudy analysis supplements previous findings that revefenacin provides sustained bronchodilation over 24 hours. Assessing additional complementary COPD clinical trial endpoints can help clinicians make treatment decisions.Keywords: Bronchodilators, long-acting muscarinic antagonist, outcome measures, spirometry, forced expiratory volume in 1 second