Gamma scintigraphic pulmonary deposition study of glycopyrronium/formoterol metered dose inhaler formulated using co-suspension delivery technology

Abstract

This gamma scintigraphy imaging study was the first to assess pulmonary and extrathoracic deposition and regional lung deposition patterns of a radiolabelled long-acting muscarinic antagonist/long-acting β-agonist fixed-dose combination glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10μg (equivalent to glycopyrrolate/formoterol fumarate 18/9.6μg), delivered by pressurized metered dose inhaler (pMDI) using novel co-suspension delivery technology. In this Phase I, randomized, single-centre, single-blind, single-dose, two-treatment, crossover, placebo-controlled study (PT003020), 10 healthy male adults received two actuations of GFF pMDI (7.2/5.0μg per actuation) and placebo pMDI (containing phospholipid-based porous particles without active pharmaceutical ingredient), both radiolabelled with Tc, up to 5MBq per actuation. Gamma scintigraphy images of lungs, stomach, head and neck were recorded. In addition, images of the actuators after use, collected mouth washings and exhalation filters were acquired. On average, 38.4% of the emitted dose of radiolabelled GFF pMDI, and 32.8% of radiolabelled placebo pMDI, was deposited in the lungs. The percentage emitted dose detected in the oropharyngeal and stomach regions was 61.4% and 66.9% for radiolabelled GFF pMDI and placebo pMDI, respectively. For both treatments, ≤0.25% of the emitted dose was detected in the exhalation filter. The normalized outer/inner ratio was 0.57 and 0.59 for radiolabelled GFF pMDI and placebo pMDI, respectively, and the standardized central/peripheral ratio was 1.85 and 1.94 respectively, indicating delivery of both co-suspension delivery technology formulations throughout the airways. There were no new or unexpected safety findings. In conclusion, both formulations were efficiently and uniformly deposited in the lungs with similar regional deposition patterns, oropharyngeal and stomach deposition, exhalation fraction and actuator-recovered dose.

A randomized study using functional respiratory imaging to characterize bronchodilator effects of glycopyrrolate/formoterol fumarate delivered by a metered dose inhaler using co-suspension delivery technology in patients with COPD

“…The homogeneous bronchodilation observed in this study supports the findings from a gamma scintigraphy study in healthy subjects,24 which found that GFF MDI was deposited in all regions of the lungs. FRI is also able to provide an image-based, numeric measure of drug deposition in the lungs17 and, using patient-specific inhalation profiles, estimated that approximately 48% of the total delivered dose of glycopyrronium and formoterol fumarate from GFF MDI could be deposited in the lungs.…”

“…FRI is also able to provide an image-based, numeric measure of drug deposition in the lungs17 and, using patient-specific inhalation profiles, estimated that approximately 48% of the total delivered dose of glycopyrronium and formoterol fumarate from GFF MDI could be deposited in the lungs. These FRI-based deposition results were higher than the gamma scintigraphy study (a 2D-imaging technique using 99m Tc radiolabels) that reported a lung deposition of 38% of the emitted dose of GFF MDI 24. In this study of patients with COPD, the simulation provided information about total drug deposition characteristics of GFF MDI and aligned them with the regional airway volume and resistance characteristics observed.…”

“…GFF MDI is formulated using co-suspension delivery technology that has demonstrated uniform delivery throughout the whole lung in vivo24 and consistent dose delivery in the presence of simulated patient-handling errors in vitro 27. This study, which evaluated the physiologic effects of GFF MDI drug delivery, evidenced bronchodilator distribution throughout the lung, resulting in improvements in airway volume, airway resistance, bronchodilation, and hyperinflation.…”

New developments in optimizing bronchodilator treatment of COPD: a focus on glycopyrrolate/formoterol combination formulated by co-suspension delivery technology

“… 101 – 104 Taylor et al used γ-scintigraphy to assess the lung deposition of GFF MDI and placebo MDI (porous particles only) in ten healthy male volunteers. 105 Both GFF MDI and placebo MDI delivered a similar proportion of the emitted dose to the lungs (mean [SD] 38.4% [10.0] and 32.8% [10.2], respectively), with a very low amount of the dose subsequently exhaled (mean [SD] 0.25% [0.26] and 0.24% [0.13], respectively). 105 The proportion of GFF MDI and placebo MDI delivered to the lungs was similar to the result in healthy volunteers who received an ICS/LABA FDC delivered by MDI (mean [SD] 34.1 [9.3]).…”

<p>Efficacy And Safety Of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler (GFF MDI) Formulated Using Co-Suspension Delivery Technology In Chinese Patients With COPD</p>

“…GFF MDI was first approved for the long-term maintenance treatment of airflow obstruction in patients with COPD in the USA in 2016 6 and is the first LAMA/LABA FDC available as an MDI. It has been shown to provide effective dose delivery to the whole lung in vivo, 7 as well as consistent aerosol performance in vitro, even in the presence of simulated patient-handling errors. 8 The pivotal Phase III PINNACLE-1 and PINNACLE-2 studies (NCT01854645 and NCT01854658) demonstrated the efficacy and safety of GFF MDI in patients with COPD from the USA, Australia, and New Zealand over 24 weeks.…”