Randomized study of the effects of Aerochamber Plus® Flow-Vu® on the efficacy, pharmacokinetics and safety of glycopyrronium/formoterol fumarate dihydrate metered dose inhaler in patients with chronic obstructive pulmonary disease. (May 2018)

• Record Type: Journal Article
• Authors: Fakih, Faisal; Spangenthal, Selwyn; Sigal, Barry; Darken, Patrick; Maes, Andrea; Siddiqui, Shahid; Gillen, Michael; Reisner, Colin; Martin, Ubaldo J.
• Is Part Of: Respiratory medicine. Volume 138(2018)
• Page Start: 74
• Page End: 80
• Publication Date: 2018-05
• Subjects: Co-suspension delivery technology -- Formoterol fumarate dihydrate -- Glycopyrronium -- Metered dose inhaler -- Spacer -- Valved holding chamber; AE adverse event -- ANOVA analysis of variance -- AUC0–12 area under the curve from 0 to 12 h -- BMI body mass index -- CFC chlorofluorocarbon -- CI confidence interval -- Cmax maximum observed plasma concentration -- Cmin lowest concentration in the dosing interval -- COPD chronic obstructive pulmonary disease -- CV coefficient of variation -- FDC fixed-dose combination -- FEV1 forced expiratory volume in 1 s -- FVC forced vital capacity -- GFF glycopyrronium/formoterol fumarate dihydrate -- GI gastrointestinal -- HFA hydrofluoroalkanes -- ICS inhaled corticosteroid -- ITT intent-to-treat -- IWRS Interactive Web-based Response System -- LABA long-acting β2-agonist -- LAMA long-acting muscarinic antagonist -- LLQ lower limit of quantification -- LSM least squares mean -- MDI metered dose inhaler -- mITT modified intent-to-treat -- NA not available -- PEFR peak expiratory flow rate -- PK pharmacokinetics -- R randomization -- SD standard deviation -- SE standard error -- TEAE treatment-emergent adverse event -- tmax time to reach maximum observed plasma concentration -- VHC valved holding chamber; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2018.03.033
• Languages: English
• ISSNs: 0954-6111

Abstract

Abstract: Objectives: This study compared the efficacy, pharmacokinetics (PK), and safety of GFF MDI (Bevespi Aerosphere ® ), a fixed-dose combination of glycopyrronium and formoterol fumarate dihydrate (14.4/10 μg) delivered by a metered dose inhaler (MDI) formulated using innovative co-suspension delivery technology, in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) with and without the Aerochamber Plus ® Flow-Vu ® valved holding chamber (VHC). Methods: In this multicenter, open-label, crossover, Phase III study (NCT02454959), patients were randomized to receive GFF MDI 14.4/10 μg (equivalent to glycopyrrolate/formoterol fumarate 18/9.6 μg) twice daily for 7 days with and without the VHC. The primary endpoint was forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1 AUC0-12 ) on Day 8. Steady state PK parameters for glycopyrronium and formoterol (AUC0-12, peak concentration [Cmax ] and time to peak concentration [tmax ]) were estimated from 12-h plasma concentration time data on Day 8. Safety and tolerability were also assessed throughout. Results: Eighty patients were randomized. On Day 8, the ratio (90% confidence interval [CI]) of least squares mean (LSM) FEV1 AUC0-12 for GFF MDI with VHC (LSM = 1538 mL; n = 67) versus without VHC (LSM = 1516 mL; n = 68) was 101.4% (100.1, 102.7). PK parameters were comparable overall with a slightly higher exposure to glycopyrronium with the VHC. The AUC0-12 geometric LSM ratio (90% CI) for GFF MDI with versus without VHC was 115.99% (99.74, 134.89) for glycopyrronium and 96.66% (86.69, 107.78) for formoterol. GFF MDI with and without VHC were well tolerated with a similar adverse event profile. Conclusions: The magnitude of bronchodilatory effect was similar with and without a VHC following GFF MDI treatment. This, together with the PK and safety profiles, supports the use of the VHC with GFF MDI for the maintenance treatment of COPD, which could be particularly useful for patients who have difficulty with the coordination of an MDI. Highlights: GFF MDI is the first LAMA/LABA fixed dose combination available as a MDI. In patients with COPD, GFF MDI treatment with or without valved holding chamber led to: Equivalent improvements in lung function endpoints Similar glycopyrronium and formoterol pharmacokinetic profiles Comparable safety profiles