James F Donohue1, Edward Kerwin2, Sanjay Sethi3, Brett Haumann4, Srikanth Pendyala4, Lorna Dean4, Chris N Barnes4, Edmund J Moran4, Glenn Crater5. 1. Pulmonary Medicine, UNC School of Medicine, Chapel Hill, NC, USA. 2. Clinical Research Institute of Southern Oregon, PC, Medford, OR, USA. 3. University at Buffalo, State University of New York, Buffalo, NY, USA. 4. Theravance Biopharma US, Inc., 901 Gateway Boulevard, South San Francisco, CA, 94080, USA. 5. Theravance Biopharma US, Inc., 901 Gateway Boulevard, South San Francisco, CA, 94080, USA. Electronic address: gcrater@theravance.com.
Abstract
BACKGROUND: Prior replicate 12-week phase 3 trials demonstrated that once-daily doses of revefenacin inhalation solution at 88 μg and 175 μg produced significant bronchodilation over 24 h post dose in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). The objective was to characterize the safety profile of revefenacin 88 μg and 175 μg over 52 weeks of treatment. METHODS: In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD receivedrevefenacin 88 μg or 175 μg in a double-blind manner, or open-label active control tiotropium. RESULTS: Treatment-emergent adverse events (AEs) were comparable across all treatment groups (n [%] patients; revefenacin 88 μg, 272 [74.7%]; 175 μg, 242 [72.2%]; tiotropium, 275 [77.2%]). Numerically fewer COPD exacerbations (n [%] patients) were observed with revefenacin 175 μg (73 [21.8%]) than with 88 μg (107 [29.4%]) or tiotropium (100 [28.1%]). Serious AEs were comparable with revefenacin 88 μg (58 [15.9%] and tiotropium (58 [16.3%]), but were lower with revefenacin 175 μg (43 [12.8%]), and mortality was low. In patients using revefenacin 88 μg or tiotropium with a concurrent long-acting β-agonist (LABA) product, the incidence of AEs was slightly higher than without concurrent LABA. LABA did not affect the incidence of AEs for patients who received revefenacin 175 μg. CONCLUSIONS:Revefenacin was generally well tolerated over 52 weeks of treatment, and had a safety profile that supports its use as a long-term once-daily bronchodilator for the nebulized treatment of COPD.
RCT Entities:
BACKGROUND: Prior replicate 12-week phase 3 trials demonstrated that once-daily doses of revefenacin inhalation solution at 88 μg and 175 μg produced significant bronchodilation over 24 h post dose in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). The objective was to characterize the safety profile of revefenacin 88 μg and 175 μg over 52 weeks of treatment. METHODS: In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 88 μg or 175 μg in a double-blind manner, or open-label active control tiotropium. RESULTS: Treatment-emergent adverse events (AEs) were comparable across all treatment groups (n [%] patients; revefenacin 88 μg, 272 [74.7%]; 175 μg, 242 [72.2%]; tiotropium, 275 [77.2%]). Numerically fewer COPD exacerbations (n [%] patients) were observed with revefenacin 175 μg (73 [21.8%]) than with 88 μg (107 [29.4%]) or tiotropium (100 [28.1%]). Serious AEs were comparable with revefenacin 88 μg (58 [15.9%] and tiotropium (58 [16.3%]), but were lower with revefenacin 175 μg (43 [12.8%]), and mortality was low. In patients using revefenacin 88 μg or tiotropium with a concurrent long-acting β-agonist (LABA) product, the incidence of AEs was slightly higher than without concurrent LABA. LABA did not affect the incidence of AEs for patients who received revefenacin 175 μg. CONCLUSIONS:Revefenacin was generally well tolerated over 52 weeks of treatment, and had a safety profile that supports its use as a long-term once-daily bronchodilator for the nebulized treatment of COPD.
Authors: Sanjay Sethi; James F Donohue; Gary T Ferguson; Chris N Barnes; Glenn D Crater Journal: Ther Adv Respir Dis Date: 2020 Jan-Dec Impact factor: 4.031
Authors: James F Donohue; Edward Kerwin; Chris N Barnes; Edmund J Moran; Brett Haumann; Glenn D Crater Journal: BMC Pulm Med Date: 2020-05-11 Impact factor: 3.317
Authors: James F Donohue; Edward Kerwin; Sanjay Sethi; Brett Haumann; Srikanth Pendyala; Lorna Dean; Chris N Barnes; Edmund J Moran; Glenn Crater Journal: Respir Res Date: 2019-10-30