Phase II Study to Evaluate the Cardiac Safety of 2 Doses of CHF5993 Both Combined With CHF1535 BID Versus CHF1535 BID in Patients With Moderate to Severe COPD

Study Overview
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Brief Summary
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Cardiac Safety Study

Detailed Description
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The purpose of this study is to demonstrate equivalence between CHF1535 plus CHF5992 (two different dosages) over CHF1535 alone in change from baseline in average 24-hour heart rate, as primary end point, and other ECG parameters.

Official Title
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Randomized, Double-Blind, Active Controlled, 3-Arm Parallel Group, Multi-National, Multi-Centre Study To Evaluate The Cardiac Safety Of Two Doses Of CHF5993 BID Delivered Via HFA PMDI Both Combined With CHF1535 BID Delivered Via HFA PMDI Versus CHF1535 BID Delivered Via HFA PMDI In Patients With Moderate To Severe COPD

Conditions
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Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: CHF1535 + CHF5992 dose 1 BID
* Drug: CHF1535 + CHF5992 dose2 BID
* Drug: CHF1535 daily dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults ≥ 40years and ≤ 80years old Male subjects: they and/or their partner must be willing to use an approved method of contraception 1) from the time of dose administration and until 30 days after the last dose of study. Subjects must not donate sperm for 30 days after the last dose of study drug Written informed consent obtained by the patient prior to any study related procedures Outpatient with diagnosis of COPD (defined in GOLD guidelines, up to date 2010) at least in the 6 months before the screening visit, including: Smoking history of at least 10 pack years defined as [(number of cigarettes smoked per day) x (number of years of smoking)]/20; both current and ex smokers are eligible. For patients who are in smoking cessation therapy this must be completed at least 1 week before study enrollment Regular use of bronchodilators (e.g. β2-agonist or/and anticholinergics) in the previous 2 months at Visit 0 Post-bronchodilator FEV1 ≥ 30% and ≤ 60% of the predicted normal value Post-bronchodilator FEV1/FVC ≤ 0.70 Exclusion Criteria: Pregnant or lactating women or all women physiologically capable of becoming pregnant UNLESS they meet the following definition of postmenopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with already documented serum FSH level > 40mlU/mL or are using one of the following acceptable methods of contraception Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy) Hormonal contraception (implantable, patch, oral) Double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation Current diagnosis of asthma or other respiratory disorders (other than COPD) which may interfere with data interpretation according to the investigator's opinion Hospitalization due to COPD exacerbation in the three months prior to screening and during run-in period or COPD exacerbation requiring systemic steroids and or antibiotics in the 6 weeks prior to screening and during run-in period. COPD exacerbation will be defined according to the following criteria: a sustained worsening of the patient condition (dyspnoea, cough and/or sputum production/purulence), from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication that includes prescription of oral corticosteroids and/or antibiotics, or need for hospitalization. Patient with COPD who requires regular long term use of oxygen therapy Patient who requires chronic mechanical ventilation for COPD Patient treated regularly with oral or parenteral corticosteroids for their COPD Change of COPD regular medication in the 4 weeks prior to enrollment Unstable CV diseases Known abnormality of any cardiac valve

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF5993 HFA pMDI dose 1, BID<br>CHF5993 HFA pMDI dose 1, BID | Drug: CHF1535 + CHF5992 dose 1 BID<br>* CHF1535 + CHF5992 dose 1 BID for 14 days<br>|
| Experimental: CHF5993 HFA pMDI dose 2, BID<br>CHF5993 HFA pMDI dose 2, BID | Drug: CHF1535 + CHF5992 dose2 BID<br>* CHF1535 + CHF5992 dose 2 BID for 14 days<br>|
| Active Comparator: CHF1535 HFA pMDI + Placebo<br>CHF1535 HFA pMDI BID plus placebo BID | Drug: CHF1535 daily dose<br>* CHF1535 daily dose for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in average 24-hour heart rate at Final visit | To assess the effect on change from baseline in average 24h Heart Rate at Day 14 of study treatment | Day 14 of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate and ECG parameters variation | Pre and post-dose | Day 1 and Day 14 of Study Treatment | 

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