Foster® pMDI (CHF 1535) Versus Symbicort® Turbohaler in COPD Patient

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate the non-inferiority of CHF1535 pMDI versus Symbicort® Turbohaler® in terms of lung function parameters and patients reported outcomes and to assess its safety and tolerability.

Official Title
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A 24-week, Double Blind, Double Dummy, Randomized, Multicentre, 2-arm Parallel Group, Active Controlled Clinical Trial of Fixed Combination of Beclometasone Dipropionate Plus Formoterol Fumarate Administered Via pMDI (CHF 1535) Versus the Fixed Combination of Budesonide Plus Formoterol Fumarate (Symbicort® Turbohaler®) in Patients With Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: CHF 1535 100/6 µg pMDI plus Symbicort® Turbohaler® Placebo
* Drug: Symbicort® Turbohaler® plus CHF 1535 pMDI Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged ≥ 40 years, Chinese ethnicity Patients with COPD diagnosed at least 12 months before the screening visit. A smoking history of at least 10 pack years Post-bronchodilator FEV1 < 50% of the predicted normal value Post-bronchodilator FEV1/FVC ratio < 0.7 One exacerbation in the 12 months prior the screening visit Exclusion Criteria: Patients requiring OCS/antibiotics/PDE inhibitors in the 4 weeks prior to screening COPD exacerbation requiring OCS/antibiotics or hospitalization during the run-in period Known respiratory disorders other than COPD Diagnosis of asthma

Ages Eligible for Study
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Minimum Age: 40 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: CHF 1535 100/6 µg pMDI<br>2 inhalations BID Total Daily Dose = 400/24µg | Drug: CHF 1535 100/6 µg pMDI plus Symbicort® Turbohaler® Placebo<br>* Fixed combination of beclometasone dipropionate 100 µg plus formoterol fumarate 6 µg (BDP/FF)<br>|
| Active Comparator: Symbicort® Turbohaler®<br>2 inhalations BID Total Daily Dose = 640/18µg | Drug: Symbicort® Turbohaler® plus CHF 1535 pMDI Placebo<br>* Fixed combination of 160 µg budesonide + 4.5 µg formoterol fumarate (BUD/FF)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstration of the non-inferiority of CHF 1535 pMDI versus Symbicort® Turbohaler® in terms of pulmonary function | Change from baseline in pre-dose morning First Expiratory Volume in 1 second (FEV1) in patients with Chronic Obstructive Pulmonary Disease (COPD) | At week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of CHF 1535 on change from baseline pre-dose morning FEV1 | FEV1 is the volume of air that can be forced out in one second after taking a deep breath. FEV1 will be measured via spirometer. | At week 4, week 12, week 18 and week 24 | 
| Effect of CHF 1535 on chnage from Baseline in pre-dose morning Force Vital Capacity (FVC) | FVC is the volume of air expired after a maximum inspiration. FVC will be measured via spirometer. | At week 4, week 12, week 18 and week 24 | 
| Effect of CHF 1535 on change from baseline in the St. George's Respiratory Questionnaire (SGRQ) total scores and domains | The SGRQ is a well-established, self-completed tool to measure impact on overall health, daily life and perceived well-being in patients with obstructive airways disease. Score range from 0 to 100 with higher scores indicating more limitations. | At week 12, week 24 | 
| Effect of CHF 1535 on change from baseline in COPD Assessment Test (CAT) | CAT is an easy questionnaire self-administered by patients. It was specifically designed to measure candidate items regarding daily symptoms, activity limitations and other manifestations of the COPD. It will be filled in at all clinical visits. | Over 28 weeks | 
| Effect of CHF 1535 on the rate of COPD exacerbations | The number of moderate and severe COPD exacerbations during the treatment period will be collected and analyzed. Moderate exacerbations require treatment with systemic corticosteroids and/or antibiotics Severe exacerbations require hospitalisation or result in death | Over 24 weeks of treatment | 
| Number of patients with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence or effect that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. | Over 29 weeks (from Visit 0 to Visit 6) | 
| Assessment of blood pressure | Systolic and diastolic blood pressure will be measured at all clinical visits from Visit 1 after 10 minutes in seated resting position. | Over 28 weeks (from Visit 1 to Visit 6) | 
| Number of subjects with abnormal Electrocardiogram (ECG) findings | Twelve-lead ECG measurements will be obtained after the subject laid in a resting position for 10 minutes. ECG will be recorded in triplicate and evaluated at Visit 1 and Visit 6. | At screening visit and week 24 | 
| Number of subjects with abnormal Haematology parameters | The following Haematology parameters will be assessed by a central laboratory: Red blood cells count (RBC), white blood cells count (WBC) and differential, total haemoglobin (Hb), hematocrit (Hct), platelets count (PLT). | At screening visit and week 24 | 
| Number of subjects with abnormal Blood Chemistry parameters | The following Blood Chemistry parameters will be assessed by a central laboratory: creatinine, BUN, fasting serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma-glutamyl transpeptidase (γ-GT), total bilirubin, alkaline phosphatase, sodium, potassium, calcium, and chloride electrolytes (Na, K, Ca, Cl), albumin. | At screening visit and week 24 | 

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