Gary T. Ferguson, MD1 Gregory Feldman, MD2 Krishna K. Pudi, MD3 Chris N. Barnes, PhD4 Edmund J. Moran, PhD4 Brett Haumann, MD, MBA4 Srikanth Pendyala, MD4 Glenn Crater, MD4
Author Affiliations
- Pulmonary Research Institute of Southeast Michigan, Farmington Hills
- South Carolina Pharmaceutical Research, Spartanburg
- Sherman Clinical Research, Sherman, Texas
- Theravance Biopharma US, Inc., South San Francisco, California
Address correspondence to:
Gary T. Ferguson, MD
Suite A
29255 West 10 Mile Road
Farmington Hills, MI 48336
Email: garytferguson@msn.com
Phone: (248) 478-6561
Abstract
Background: Revefenacin, a novel, lung-selective, long-acting muscarinic antagonist, has been developed for nebulized therapy for chronic obstructive pulmonary disease (COPD). We present the results of replicate Phase III efficacy and safety studies of revefenacin in patients with moderate to very severe COPD.
Methods: In 2 double-blind, parallel-group studies, (Study 0126 and Study 0127), patients ≥ 40 years old were randomized to revefenacin 88 μg, revefenacin 175 μg or placebo administered once daily by standard jet nebulizer for 12 weeks. The primary endpoint was 24-hour trough forced expiratory volume in 1 second (FEV1) on day 85. Secondary efficacy endpoints included overall treatment effect (OTE) on trough FEV1 and peak FEV1 (0-2 hours after first dose). Safety assessments included treatment-emergent adverse events.
Results: At day 85, revefenacin 88 µg and 175 µg improved trough FEV1 versus placebo in Study 0126 (by 79 mL [p=0.0003] and 146 mL [p<0.0001]) and Study 0127 (by 160 mL and 147 mL; both p<0.0001). Compared with placebo, pooled data of revefenacin 88 µg and 175 µg increased OTE trough FEV1 by 115 mL and 142 mL (both p<0.001) and increased peak FEV1 by 127 mL and 129 mL (both p<0.0001). Revefenacin 175 µg demonstrated greater improvements in FEV1 in concomitant long-acting beta2-agonist patients and in more severe patients than revefenacin 88 µg. Adverse events were minor.
Conclusions: Revefenacin, administered once daily for 12 weeks to patients with moderate to very severe COPD, demonstrated clinically significant improvements in trough FEV1 and OTE FEV1. Revefenacin was generally well tolerated with no major safety concerns.
Citation
Citation: Ferguson GT, Feldman G, Pudi KK, et al. Improvements in lung function with nebulized revefenacin in the treatment of patients with moderate to very severe COPD: results from two replicate phase III clinical trials. J COPD F. 2019; 6(2): 154-165. doi: http://doi.org/10.15326/jcopdf.6.2.2018.0152