Glycopyrronium Bromide Delivered by Dry Powder Inhaler vs eFlow Nebulizer in COPD

In patients with chronic obstructive pulmonary disease (COPD), glycopyrronium bromide (GLY) delivered by a dry powder inhaler (GLY/DPI) may be associated with a higher peak and steadier state levels of drug compared with GLY delivered by the novel eFlow^® closed system (CS) vibrating membrane nebulizer (GLY/eFlow), according to study results published in Respiratory Research.

Researchers included 30 patients with moderate to severe COPD (mean age, 60.5 years) in the GOLDEN7 randomized clinical trial (ClinicalTrials.gov Identifier: NCT02512302). After a 3-week screening period for medication washout, participants were randomly assigned to either 50 μg GLY/eFlow or 63 μg GLY/DPI, with and without activated charcoal. The eFlow CS device is a portable, handheld nebulizer that delivers nebulized GLY for maintenance of airflow obstruction in COPD. Treatment was followed by an intravenously administered dose of 50 μg GLY accompanied by a 7-day washout period between each dose.

At baseline, the mean predicted forced expiratory volume in 1 second (FEV₁) was 51%±15%. The absolute systemic bioavailability of GLY/eFlow without charcoal was 15%, whereas the absolute systemic bioavailability for GLY/DPI was 22%. Adding activated charcoal was associated with a 10% reduction of maximum observed plasma concentration and area under the concentration-time curve from 0 to 24 hours. In addition, there was a greater change in FEV₁ from baseline with GLY/DPI vs GLY/eFlow without charcoal (0.220 L vs 0.180 L, respectively). When charcoal was administered, there were similar improvements in FEV₁ (0.220 L for both groups). A fewer number of patients in the GLY/eFlow group had adverse events (n=15) vs the GLY/DPI group (n=18).

Limitations of the study included the small number of participants, the lack of a healthy control group, and the inclusion of patients who were trained to use the DPI device.

“A relevant aspect of determining the appropriate device for a patient is their preference,” the researchers wrote, “which also may be related to a better quality of life due to improved treatment satisfaction.”

Disclosures: Several authors are employees of Sunovion Pharmaceuticals, Inc, which funded the study.

Reference

Leaker BR, Singh D, Nicholson GC, et al. Evaluation of systemic absorption and bronchodilator effect of glycopyrronium bromide delivered by nebulizer or a dry powder inhaler in subjects with chronic obstructive pulmonary disease. Respir Res. 2019;20(1):132.