NEW ORLEANS — In patients with chronic obstructive pulmonary disease (COPD), revefenacin demonstrated a safety profile similar to that of formoterol alone when given either before or combined with formoterol through a standard jet nebulizer, according to research results presented at the CHEST Annual Meeting, held October 19 to 23, 2019, in New Orleans, Louisiana.
The Global Initiative for Chronic Obstructive Lung Disease recommends using 2 long-acting bronchodilators for patients with COPD who remain symptomatic despite the use of a single long-acting bronchodilator. Although there is no nebulized form of dual bronchodilator currently available, the approval of the once-daily, long-acting muscarinic antagonist (LAMA) revefenacin would allow for the delivery of a LAMA and a long-acting beta agonist (LABA), such as formoterol, via standard jet nebulizer.
Therefore, researchers conducted this randomized, double-blind, 2-period, parallel-group, 42-day trial (ClinicalTrials.gov Identifier: NCT03573817). They randomly assigned 122 patients with moderate to very severe COPD to receive 175 μg revefenacin (n=63) or placebo (n=59) followed by 20 μg formoterol via standard jet nebulizer (sequential delivery) each morning and evening for 21 days. Participants then continued another 21 days of treatments, but for this phase of therapy, the revefenacin or placebo and formoterol were administered as combined solutions via a single nebulization in the morning, and formoterol was given as a single treatment in the evening. Participants who took inhaled corticosteroids at baseline were allowed to continue to use their inhalers throughout the trial.
The primary goal was to establish a safety profile for revefenacin and formoterol nebulized therapy over each 21-day treatment period, as assessed by vital signs, electrocardiogram, laboratory monitoring, adverse events (AEs), and serious AEs (SAEs). Forced expiratory volume in 1 second (FEV1) was measured at baseline, day 21, and day 42.
Among the total 122 participants (mean age, 64 years; 95% white, 57% men, and 57% smokers), the mean FEV1was 55% predicted, and 24% were taking inhaled corticosteroids. The following minimal AEs were seen across all groups: revefenacin-formoterol sequential (oropharyngeal pain [1.6%]); placebo-formoterol sequential (COPD [3.4%], dizziness [3.4%]); revefenacin-formoterol combined (COPD [1.6%]); placebo-formoterol combined (cough [3.6%], oropharyngeal pain [1.6%]). There were no SAEs reported in any group, nor changes in vital signs, heart rate, QT-corrected for heart rate using Fridericia’s method, or laboratory results. In the revefenacin-formoterol sequential groups, the least squares mean in trough FEV1 vs baseline over each 21-day treatment period was 157.1 mL, compared with 53.3 mL in the placebo-formoterol sequential group, 115.6 mL in the revefenacin-formoterol combined group, and 35.0 mL in the placebo-formoterol combined group.
“Trough FEV1 response was similar when [revefenacin] was given sequentially or combined with [formoterol], with [revefenacin] providing an additional 81-104 mL improvements over FOR alone,” the investigators concluded. “Sequential or combined delivery of a LAMA and LABA via a standard jet nebulizer could be a treatment option for patients with COPD.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Siler T, Moran E, Yun J, Barnes C, Crater G. Tolerability and efficacy of revefenacin when administered with formoterol via nebulization. Presented at: CHEST Annual Meeting; October 19-23, 2019; New Orleans, LA. Abstract 1160.