Efficacy of Fixed Combination of Beclometasone + Formoterol + Glycopyrrolate Versus Foster® in COPD

A Phase 3 Randomised Double Blind Randomised Parallel Multinational Trial Comparing a Fixed Combination of Beclometasone + Formoterol + Glycopyrrolate to Foster® in Patients With Chronic Obstructive Pulmonary Disease

Randomized,double-blind,multicenter,multinational,parallel-group,Phase III study to demonstrate the superiority of the triple fixed combination of beclometasone + formoterol + glycopyrrolate (BDP/FF/GB) administered via pressurised metered dose inhaler (pMDI) over the equivalent dose of Foster® (beclometasone dipropionate (BDP) / formoterol fumarate (FF), in patients diagnosed with chronic obstructive pulmonary disease (COPD) after 52 weeks of treatment.

This 52-week randomised 2 parallel groups study evaluated the superiority of fixed triple therapy with Inhaled Corticosteroid (ICS) / Long-Acting β2-Agonist (LABA) / Long-Acting Muscarinic Antagonist (LAMA) compared with ICS/LABA in patients with severe to very severe diagnosed of COPD.

Patients' eligibility was checked during the screening visit including the review of medical history, spirometry assessments, routine labs, physical examination, 12-lead electrocardiogram (ECG), vital signs measurement, prior to entering a 2-week open-label run-in period with BDP/FF to establish a baseline.

After the run-in period, eligible patients were randomised, to either fixed triple therapy BDP/FF/GB or BDP/FF treatment group. During the 52-week treatment period, patients who completed the study did have 5 subsequent visits post randomisation scheduled respectively after 4, 12, 26, 40, and 52 weeks of treatment. During these visits, pre-dose and post-dose spirometry, 12-lead ECG, vital signs, and dyspnoea assessments were performed. Rescue medication use, compliance with the treatment, and EXACT-PRO questionnaire [EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): a patient-reported outcome (PRO)] were recorded daily (via an electronic diary) during the run-in and randomised treatment periods.

For pharmacovigilance purposes, adverse events (AE) were recorded from the time of patient informed consent signature until subject's study participation ended (Week 52 or early discontinuation).

Inclusion Criteria:

• Male or female adults aged ≥ 40 years with a diagnosis of COPD
• Current smokers or ex-smokers
• A post-bronchodilator Forced Expiratory Volume in the 1st Second (FEV1) < 50% of the predicted normal value and a post- bronchodilator FEV1/ Forced Vital Capacity (FVC) < 0.7
• At least one exacerbation in the 12 months preceding the screening visit

Exclusion Criteria:

• Pregnant or lactating women
• Diagnosis of asthma or history of allergic rhinitis or atopy
• Patients treated with non-cardioselective β-blockers in the month preceding the screening visit
• Patients treated for exacerbations in the 4 weeks prior to screening visit
• Patients treated with long-acting antihistamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study or if taken as PRN
• Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
• Known respiratory disorders other than COPD
• Patients who have clinically significant cardiovascular condition