Pudi KK, et al. - Researchers performed this multiple-dose study to characterize the bronchodilation efficacy and adverse events profile of patients with chronic obstructive pulmonary disease (COPD) who were administered revefenacin once daily by a standard jet nebulizer, for 28 days. Findings indicated that 88 and 175 μg revefenacin are appropriate doses for use in longer-term safety and efficacy trials. Notably, for COPD patients who need or prefer a nebulized drug delivery option, revefenacin offers the potential for the first once-daily long-acting muscarinic antagonist (LAMA) for nebulization.

Methods

• In this double-blind, placebo-controlled parallel group study, researchers randomized a total of 355 COPD patients (mean age 62 years, mean forced expiratory volume in 1 s [FEV₁] 44% of predicted).
• Inhaled corticosteroids as well as short-acting bronchodilators were permitted.
• Using a standard jet nebulizer, once-daily treatments (44, 88, 175 or 350 μg revefenacin or matching placebo) were administered for 28 days.
• Change from baseline in D28 trough FEV₁ was the primary endpoint, and weighted mean FEV₁ over 0 to 24 h and rescue medication (albuterol) use were secondary endpoints.
• In addition, safety evaluations included adverse events, laboratory assessments, electrocardiograms and 24-h Holter profiles.

Results

• Findings demonstrated that revefenacin (88, 175 and 350 μg) significantly improved D28 trough FEV₁ over placebo (187.4, 166.6 and 170.6 mL, respectively, all p < 0.001); 44 μg produced a sub-therapeutic response.
• Researchers found that at doses ≥88 μg, more than 80% of patients achieved at least a 100-mL increase from baseline FEV₁ in the first 4 h post dose compared with 33% of placebo patients.
• They also noted that for doses ≥88 μg, D28 24 h weighted mean differences from placebo for FEV₁ were numerically similar to respective trough FEV₁ values, suggesting bronchodilation was sustained for 24 h post dose.
• Data showed that doses ≥88 μg reduced the average number of albuterol puffs/day by more than one puff/day.
• In addition, results revealed that the 350 μg dose did not demonstrate additional efficacy over that observed with 175 μg revefenacin.
• Data demonstrated that revefenacin was generally well tolerated, with minimal reports of systemic anti-cholinergic effects.