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.

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 (FEV) on day 85. Secondary efficacy endpoints included overall treatment effect (OTE) on trough FEV and peak FEV (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 FEV versus placebo in Study 0126 (by 79 mL [=0.0003] and 146 mL [<0.0001]) and Study 0127 (by 160 mL and 147 mL; both <0.0001). Compared with placebo, pooled data of revefenacin 88 µg and 175 µg increased OTE trough FEV by 115 mL and 142 mL (both <0.001) and increased peak FEV by 127 mL and 129 mL (both <0.0001). Revefenacin 175 µg demonstrated greater improvements in FEV in concomitant long-acting beta2-agonist patients and in more severe patients than revefenacin 88 µg. Adverse events were minor.

CONCLUSION

Revefenacin, administered once daily for 12 weeks to patients with moderate to very severe COPD, demonstrated clinically significant improvements in trough FEV and OTE FEV. Revefenacin was generally well tolerated with no major safety concerns.