Efficacy and Safety of Glycopyrronium/Formoterol Fumarate Fixed-dose Combination Relative to Umeclidinium/Vilanterol Fixed-dose Combination Over 24 Weeks in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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This is a phase IIIb randomised, double-blind, double-dummy, multicentre, parallel group, 24 week study to assess the efficacy and safety of Glycopyrronium/Formoterol Fumarate (GFF) fixed-dose combination 7.2/4.8 μg 2 inhalations twice daily compared to Umeclidinium/Vilanterol (UV) 62.5/25 μg fixed-dose combination 1 inhalation once daily in Patients with moderate to very severe COPD.

Official Title
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A Randomised, Double-Blind, Double-Dummy, Multicentre, Parallel Group Study to Assess the Efficacy and Safety of Glycopyrronium/Formoterol Fumarate Fixed-dose Combination Relative to Umeclidinium/Vilanterol Fixed-dose Combination Over 24 Weeks in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (AERISTO)

Conditions
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Chronic Obstructive Pulmonary Disease COPD

Intervention / Treatment
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* Drug: Glycopyrronium/Formoterol Fumarate
* Drug: umeclidinium/vilanterol


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age 40-95 years at screening Current or former smoker with a history of at least 10 pack-years of cigarette smoking Current clinical diagnosis of COPD, with COPD symptoms > 1 year prior to screening, as defined by GOLD criteria or other current guidelines COPD Severity defined by FEV1/FVC ratio <0.70 and FEV1 <80% of predicted normal value at screening and at randomisation COPD treatment with rescue medication only, or stable dose of maintenance monotherapy (LAMA, LABA or ICS), or stable dose of double maintenance therapy (LAMA/LABA or ICS/LABA), for one month prior to screening COPD Assessment Test (CAT) score ≥10 at randomisation Documentation of a chest x-ray (as per local practice) or computed tomography (CT) within 6 months prior to screening, with no clinically significant pulmonary abnormalities other than related to COPD Exclusion criteria: Respiratory disease other than COPD, including: Current diagnosis of asthma Alpha-1 Antitrypsin Deficiency as the cause of COPD Other respiratory disorders and conditions as listed in the protocol Severe COPD exacerbation (resulting in hospitalisation) not resolved within 8 weeks prior to screening, or moderate exacerbation not resolved within 4 weeks, or during screening Pneumonia or lower respiratory tract infection that required antibiotics within 8 weeks prior to screening, or during screening. Significant diseases or conditions other than COPD which may put the patient at risk, or influence the results of the study or the patient's ability to participate, including cardiac disease, advanced renal disease, and cancer that has not been in complete remission for at least 5 years. Patients who have needed additions or alterations to their usual maintenance therapy for COPD due to worsening symptoms within 1 month prior to and during screening Treatment with depot corticosteroids within 6 weeks, or other systemic corticosteroids within 4 weeks, prior to screening. (Patients maintained on an equivalent of 5 mg prednisone per day for at least 3 months prior to screening are allowed.)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>glycopyrronium/formoterol fumarate 7.2/4.8 μg per actuation, twice daily | Drug: Glycopyrronium/Formoterol Fumarate<br>* Metered dose inhaler (MDI), contains glycopyrronium/formoterol fumarate fixed-dose combination 7.2/4.8 μg per actuation<br>|
| Active Comparator: Active comparator<br>umeclidinium/vilanterol 62.5/ 25μg per inhalation, once daily | Drug: umeclidinium/vilanterol<br>* Dry powder inhaler (DPI), Each metered dose contains umeclidinium/vilanterol 62.5/ 25μg fixed-dose combination per inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Morning Pre-dose Trough Forced Expiratory Volume in 1 Second (FEV1) Over 24 Weeks | To assess the effects of GFF relative to UV on lung function as measured by change from baseline in morning pre-dose trough FEV1 is defined as the average of the -60 and -30 minute pre-dose values at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1). BR a/s = bronchodilator responsiveness to albuterol/salbutamol. | From Baseline (Day 1) up to 24 weeks | 
| Mean Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks in PP Analysis Set Population | To assess the effects of GFF relative to UV on lung function in PP analysis set population as measured by peak change from baseline in FEV1 is defined as the maximum of the FEV1 assessments within the 2 hours post-dosing time windows at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1). | From Baseline (Day 1) up to 24 weeks | 
| Mean Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks in FAS Population | To assess the effects of GFF relative to UV on lung function in FAS population as measured by peak change from baseline in FEV1 is defined as the maximum of the FEV1 assessments within the 2 hours post-dosing time windows at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1). | From Baseline (Day 1) up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Increase of FEV1 of >=100 mL From Baseline at 5 Minutes Post-dosing on Day 1 | The percentage of participants with an increase in FEV1 of >=100 mL from baseline at 5 minutes post-dosing on Day 1 was determined to assess the early onset of action. Baseline is defined as the average of available evaluable -60 and -30 minute pre-dose assessments conducted at randomization (Day 1). Only data assigned to the 5 minute window was used to determine response. Participants with missing data were considered non-responders for the analysis. | 5 minutes post-dose on Day 1 | 
| Mean Peak Change From Baseline in Inspiratory Capacity (IC) Within 2 Hours Post-dosing Over 24 Weeks | Peak change from baseline in IC is defined as the maximum of the IC assessments within the 2 hours post-dosing time windows at each visit minus baseline. Baseline is defined as the average of available evaluable -60 and -30 minute pre-dose assessments conducted at randomization (Day 1). | From Baseline (Day 1) up to 24 weeks | 
| Mean Transition Dyspnea Index (TDI) Focal Score Over 24 Weeks | The baseline dyspnea index (BDI) and TDI consist of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these 3 components were rated in 5 grades from 0 (very severe) to 4 (no impairment), and were summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea were rated for each component by 7 grades from -3 (major deterioration) to +3 (major improvement), and were added to form a TDI focal score from -9 to +9. Baseline is defined as the latest BDI assessment within 7 days before or at randomization (Day 1). | From Baseline (Day -7 or 1) up to 24 weeks | 
| Mean Change From Baseline in Early Morning Symptoms of COPD Instrument (EMSCI) Over 24 Weeks | Change from baseline in the 6-item EMSCI Symptom Severity Score was derived by averaging the responses from a participant on the 6 item-level symptom scores (scored on a 4-point scale from 1 to 4, whereas 1= mild and 4= very severe). The EMSCI collected data about the frequency and severity of early morning symptoms and the impact of COPD symptoms on early morning activity in participants with COPD. Participants completed a daily electronic patient-reported outcome (ePRO) questionnaire for their COPD symptoms. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1). TI = Time interval. | From Baseline (Day -7) up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD