Safety and Efficacy Study of Treatment With Single Doses of CHF 4226 pMDI in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of this study is to characterize the dose-response profile of peak and trough FEV1 after single dose administrations of carmoterol in patients with COPD.

Official Title
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EVALUATION OF THE SAFETY AND EFFICACY OF TREATMENT WITH SINGLE DOSES OF CHF 4226 pMDI IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE A Multicenter, Randomized, Double-Blind,Placebo-Controlled, 5-Way Crossover Study

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: CHF 4226 pMDI
* Drug: CHF 4226 pMDI
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has signed an IRB approved Informed Consent form and the written informed consent was obtained prior to any study-related procedure(s) Patient is a male or non-pregnant female, 40 -75 years old, inclusive Patient has a current or past cigarette smoking history of at least 15 pack-years Patient has a clinical diagnosis of COPD in accordance with the recommendations of the National Heart Lung and Blood Institute/World Health Organization (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) Patient meets the following requirements after an FEV1 albuterol reversibility test (i.e., 30 minutes following 400µg (metered dose) albuterol MDI): FEV1/FVC < 70% FEV1 is at least 0.9L FEV1 30% - 80%, inclusive, of patient's predicted normal value ∆FEV1 > 5% of pre-albuterol value If ∆FEV1 </= 5% of pre-albuterol value, then this requirement must be met after retesting during the run-in period, at least 24 hours prior to Visit 2. Exclusion Criteria: Patient has a history of asthma Patient has a blood eosinophil count > 500/µL Patient has a history of allergic rhinitis or atopy Patient had a COPD exacerbation or a lower respiratory tract infection within 8 weeks prior to screening, or during the run-in period, that resulted in the use of an antibiotic, or oral or parenteral corticosteroids Patient is on an inhaled corticosteroid that has been initiated, or the effective dose has been changed, within 4 weeks prior to screening or during the run-in period Patient has an uncontrolled cardiovascular (e.g., uncontrolled hypertension), respiratory, hematologic, immunologic, renal, neurologic, hepatic, endocrine (e.g., uncontrolled diabetes mellitus) or other disease, or any condition that might, in the judgment of the Investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study Patient has clinically significant abnormal routine hematology (e.g., anemia) and/or clinical chemistry value(s). Patient has a history of coronary artery disease, cerebrovascular disease, cardiac arrhythmias Patient has lung cancer or a history of lung cancer Patient has active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized basal cell carcinoma (without metastases) of the skin is acceptable. Patient has a serum potassium value ≤ 3.5 mEq/L or > 5.5mEq/L and/or a fasting serum glucose value ≥ 140 mg/dL Patient has an abnormal QTcF interval value in the Screening visit ECG test (i.e., > 450 msec in males or > 470 msec in females) Patient has developed Cor Pulmonale Patient is receiving long term oxygen therapy, i.e., > 16 hours/24-hour period, every day, unless residing at an elevation > 4000ft Patient has used any of the following medications prior to Screening and has not met the specified minimum washout period: Long acting anti-cholinergic agent (i.e., tiotropium): 7 days Short acting anti-cholinergics: 8 hours Fixed combinations of β2-agonists and inhaled corticosteroids: 48 hours Fixed combinations of an anti-cholinergic and short acting β2-agonist: 8 hours Long-acting β2-agonists: 48 hours Short acting β2-agonists: 6 hours Theophylline and other xanthines: 1 week Parenteral or oral corticosteroids: 1 month Patient has taken any non-permitted medication Patient has received a live-attenuated virus vaccination within two weeks prior to screening or during the run-in (inactivated Influenza vaccination is acceptable provided it is not administered within 48 hours prior to Screening) Patient has a known intolerance/hypersensitivity to β2-adrenergic agonists, propellant gases/excipients Patient is pregnant or lactating female, or female physiologically capable of becoming pregnant UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL OR are using one or more 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) Patient is male and does not agree to use a medically acceptable contraceptive (abstain from sexual intercourse, or use a condom with spermicide), or has not had a vasectomy at least 6 months prior to study participation, unless their sexual partner is not of child-bearing potential Patient is mentally or legally incapacitated Patient has participated in another investigational study within 30 days prior to screening Patient abuses alcohol or other substances Patient does not maintain regular day/night, waking/sleeping cycles (e.g., night shift worker) Patient is potentially non-compliant or unable to perform required outcome measurements of the protocol

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Treatment A<br>Single therapeutic dose of CHF 4226 pMDI | Drug: CHF 4226 pMDI<br>* Inhaled solution, single therapeutic dose<br>|
| Experimental: Treatment B<br>Single therapeutic dose of CHF 4226 pMDI | Drug: CHF 4226 pMDI<br>* Inhaled solution, single therapeutic dose<br>|
| Experimental: Treatment C<br>Single supratherapeutic dose of CHF 4226 pMDI | Drug: CHF 4226 pMDI<br>* Inhaled solution, single supratherapeutic dose<br>|
| Experimental: Treatment D<br>Single supratherapeutic dose of CHF 4226 pMDI | Drug: CHF 4226 pMDI<br>* Inhaled solution, single supratherapeutic dose<br>|
| Placebo Comparator: Treatment E<br>Single dose of placebo | Drug: Placebo<br>* Inhaled solution, single dose of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 |  | T-1hr, T-10min, and 15 and 30 minutes, 1, 2, 3, 23 and 24 hours for each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum potassium |  | pre dose and 1, 4, 6 and 24 hrs post dose for each treatment period | 
| serum glucose |  | pre dose and 1, 4, 6 and 24 hrs post dose for each treatment period | 
| plasma concentrations of CHF 4226 |  | pre dose and 15 minutes and 2 hours post dose for each treatment period | 
| urinary excretion of CHF 4226 |  | pre dose and 0-24 hrs post dose for each treatment period | 
| FVC |  | T-1hr, T-10min, and 15 and 30 minutes, 1, 2, 3, 23 and 24 hours for each treatment period |