Safety, Tolerability and Efficacy of 28-day Inhaled CHF 6001 DPI in COPD Patients

Study Overview
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Brief Summary
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Phase IIa study in COPD patients aimed to evaluate the safety, tolerability ,pharmacodynamics (effect on biological markers of inflammation in induced sputum and in blood, and on pulmonary function) and on pharmacokinetics of CHF 6001 (a PDE4 inhibitor) after 28-days of daily inhaled dosing.

Official Title
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A Randomised, Double-blind, Double-dummy, Placebo and Active-controlled, Three-way Crossover Study to Evaluate the Safety, Tolerability and Efficacy of 28-day Inhaled CHF 6001 DPI (1200 µg Daily) in Subjects With COPD

Conditions
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COPD

Intervention / Treatment
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* Drug: CHF6001 DPI
* Drug: Roflumilast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained prior to any study-related procedures. Male or female aged between 40 and 70 years inclusive. Current or past smoker of at least 10 pack/years BMI in the range of 18-35 Kg/m2 GOLD Stage 2 and 3 COPD subjects A history of chronic bronchitis defined as chronic cough and sputum production At screening, subjects must be able to produce an adequate induced sputum sample Female subjects: post-menopausal women having at least 12 months of natural (spontaneous) amenorrhea, or women of childbearing potential using two acceptable methods of contraception for the duration of the study and for the following three months Exclusion criteria: Female subjects: pregnant or lactating women Past or current history of asthma History of clinically significant hypotensive episodes History or symptoms of significant cardiovascular disease History or symptoms of significant neurological disease Unstable concurrent disease An abnormal and clinically significant 12-lead ECG Clinically relevant abnormal laboratory values Use of oral or systemic corticosteroids oral and/or nebulised Beta2 agonists and/or antibiotics within 6 weeks preceding the screening visit Moderate or severe hepatic impairment (Child-Pugh B or C) Intolerance/hypersensitivity or any contraindication to treatment with roflumilast, tiotropium bromide or salbutamol or any of the excipients contained in the formulations used in the study Chronic use of any other medication for treatment of lung disease like xanthines, antileukotrienes, systemic and inhaled corticosteroids, long acting beta2- agonists, roflumilast (other than the study drug) and cromoglycates Long term (at least 12 hours daily) use of oxygen therapy for chronic hypoxemia. Having received an investigational medicinal drug within 30 days prior to study entry Blood draws of 250 mL or more within 45 days prior to enrolment into the study. Known respiratory disorders other than COPD. History of alcohol dependency, or substance abuse Inability to comply with the study Protocol for any other reason.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF6001<br>CHF6001 DPI (Dry Powder Inhaler) once daily | Drug: CHF6001 DPI<br> <br> |
| Active Comparator: Roflumilast<br>Roflumilast, tablet, once daily | Drug: Roflumilast<br> <br> |
| Placebo Comparator: placebo<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, adverse drug reactions, serious adverse. | The number and percentage of subjects experiencing AEs, ADRs, serious AEs and AEs leading to study withdrawal. | After 28 days of treatment | 
| Vital signs |  | After 28 days of treatment | 
| 12-lead ECG parameters |  | After 28 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of CHF 6001 and its metabolites |  | After 28 days of treatment | 
| Induction of sputum | Biomarkers of inflammation | After 28 days of treatment | 
| Baseline Dyspnea Index and Transition Dyspnea Index Questionnaire |  | After 28 days of treatment | 
| Lung function measurements |  | After 28 days of treatment |