Improved lung function and patient-reported outcomes with co-suspension delivery technology glycopyrrolate/formoterol fumarate metered dose inhaler in COPD: a randomized Phase III study conducted in Asia, Europe, and the USA

Abstract

BackgroundCOPD is a major global cause of mortality and morbidity. PINNACLE-4 evaluated the efficacy and safety of GFF MDI (glycopyrrolate/formoterol fumarate metered dose inhaler) in patients from Asia, Europe, and the USA with moderate-to-very severe COPD.MethodsIn this double-blind, placebo-controlled, Phase III study, patients were randomized to treatment with GFF MDI 18/9.6 μg, glycopyrrolate (GP) MDI 18 μg, formoterol fumarate (FF) MDI 9.6 μg, or placebo MDI (all twice daily) for 24 weeks. Lung function, patient-reported outcomes (symptoms and health-related quality of life), and safety were assessed.ResultsOf the 1,756 patients randomized, 1,740 patients were included in the intent-to-treat population (mean age 64.2 years, 74.1% male, and 40.2% Asian). GFF MDI significantly improved morning predose trough FEV1 at Week 24 (primary endpoint) vs placebo MDI, GP MDI, and FF MDI (least squares mean differences: 165, 59, and 72 mL, respectively; all P<0.0001). GFF MDI also significantly improved other lung function endpoints vs placebo MDI, GP MDI, and FF MDI and patient-reported outcomes vs placebo MDI and GP MDI. A larger proportion of patients treated with GFF MDI achieved the minimum clinically important difference in Transition Dyspnea Index score vs GP MDI and placebo MDI and in St George’s Respiratory Questionnaire score vs placebo MDI. Adverse event rates were similar across treatment groups.ConclusionThese results demonstrated the efficacy of GFF MDI in patients with moderate-to-very severe COPD. GFF MDI was well tolerated, with a safety profile commensurate with long-acting bronchodilators.

Pharmacokinetics and Tolerability of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate and Glycopyrronium/Formoterol Fumarate Dihydrate Metered Dose Inhalers in Healthy Chinese Adults: A Randomized, Double-blind, Parallel-group Study

“…[20,25] Additionally, the clinical efficacy and tolerability of BGF MDI and GFF MDI have been assessed in global populations with COPD, including patients from China. [7,11]. BGF MDI 320/14.4/10 mg, BGF MDI 160/14.4/10 mg, and GFF MDI 14.4/10 mg were well tolerated in these healthy Chinese subjects, and findings on tolerability were consistent with those from previous studies of BGF MDI in Western and Japanese healthy subjects, [14e16] and with the well-characterized safety profile of GFF MDI in patients with COPD.…”

<p>Patient Characteristics and Healthcare Resource Utilization Among Patients with COPD New to LAMA/LABA Fixed-Dose Combination Treatment in US-Based Real-World Practice</p>

“…These findings are generally aligned with the established characteristics of US and European patients with COPD in clinical studies of LAMA/LABA FDCs. [11][12][13][14][15] The majority of patients (75.3%) who had used an inhaled medication in the 12 months prior to the index date used a short-acting bronchodilator with or without maintenance treatment; 76.3% of these patients used a pMDI. Overall, the use of pMDIs was common in…”

“…23,24 Use of a device that the patient is familiar with can result in consistency of use and improved clinical results. 14,[25][26][27][28][29] Nevertheless, education of patients in the correct use of inhalation devices is a crucial consideration, regardless of their prior experience. 5 It was observed that patients were primarily managed in primary care (mean visits of 6.6 Figure 3 Inhaled medication history (in the 12 months prior to the index date) of patients based on inhaler type.…”

“…6 LAMA/LABA FDC therapies currently approved for the maintenance treatment of COPD in the USA are umeclidinium/vilanterol 62.5/25.0 µg (Anoro ® Ellipta ® ; approved December 2013), 7 tiotropium/olodaterol 5.0/5.0 µg (Stiolto ® Respimat ® ; approved May 2015), 8 glycopyrrolate/formoterol fumarate 18/9.6 μg (Bevespi Aerosphere™; approved April 2016), 9 and indacaterol/glycopyrrolate 27.5/15.6 µg (Utibron™ Neohaler ® ; approved October 2015). 10 These treatments have demonstrated benefits in patients with moderate-to -very severe COPD for lung function and health status, including patient-reported outcomes, versus placebo [11][12][13][14] and their specific monocomponents. [11][12][13][14][15] Real-world evidence on prescribing trends and clinical characteristics of patients initiating treatment with LAMA/ LABA FDC therapies is generally limited to data from studies that focus on the effectiveness of treatment in the period following initiation, 16,17 or is confined to evaluations of a very limited number of FDC therapies, as determined by limited clinical availability in the study population.…”

“…10 These treatments have demonstrated benefits in patients with moderate-to -very severe COPD for lung function and health status, including patient-reported outcomes, versus placebo [11][12][13][14] and their specific monocomponents. [11][12][13][14][15] Real-world evidence on prescribing trends and clinical characteristics of patients initiating treatment with LAMA/ LABA FDC therapies is generally limited to data from studies that focus on the effectiveness of treatment in the period following initiation, 16,17 or is confined to evaluations of a very limited number of FDC therapies, as determined by limited clinical availability in the study population. 16,18 To our knowledge, this is the first study to describe the demographic and clinical characteristics, healthcare resource utilization (HCRU), and treatment patterns in patients with COPD in the USA who have initiated any LAMA/LABA FDC treatment.…”