Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
The purpose of this study is to confirm the dose of CHF 4226 (carmoterol) that should be given once a day to patients with COPD in order for the effect to last for 24 hours.
Interventions
carmoterol (CHF 4226) 2 μg once a day, in the morning (1 puff of carmoterol 2 μg + 1 puff of placebo pMDI)
DRUGplacebo
placebo once a day, in the morning (1 puff of placebo pMDI + 1 puff of placebo pMDI)
DRUGsalmeterol
Salmeterol 50 μg twice daily, in the morning and in the evening (1 blister of Serevent Diskus BID)
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Signed IRB approved Informed Consent form * Male or non-pregnant female, 40 -75 years old, inclusive * Current or past cigarette smoking history of at least 15 pack-years * Clinical diagnosis of COPD in accordance with recommendations of the National Heart Lung and Blood Institute/World Health Organization (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) * Patient meets following requirements after FEV1 albuterol reversibility test (i.e., 30 minutes after 200μg (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, requirement must be met after retesting during run-in period, at least 24 hours prior to Period 1/Visit 1.
Exclusion criteria
* History of asthma * Blood eosinophil count \> 500/microliters * History of allergic rhinitis or atopy * COPD exacerbation or lower respiratory tract infection within 8 weeks prior to screening, or during run-in period, that resulted in use of an antibiotic, or oral or parenteral corticosteroids * Inhaled corticosteroid that has been initiated, or effective dose has been changed, within 4 weeks prior to screening or during run-in period * 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 Investigator's judgment, place patient at undue risk or potentially compromise study results or interpretation * History of coronary artery disease, cerebrovascular disease, cardiac arrhythmias * Lung cancer or history of lung cancer * Active cancer or history of cancer with \< 5 years disease free survival time (with or without evidence of local recurrence or metastases). Localized basal cell carcinoma (without metastases) of skin is acceptable. * Serum potassium value ≤ 3.5 mEq/L or \> 5.5mEq/L and/or fasting serum glucose value ≥ 140 mg/dL * Abnormal QTcF interval value in Screening visit ECG test (i.e., \> 450 msec in males or \> 470 msec in females) * Cor Pulmonale * Long term oxygen therapy, i.e., \> 16 hours/24-hour period, every day, unless patient resides at elevation \> 4000ft * Use of any of the following medications prior to Screening, without meeting 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 (other than those prescribed in the study): 6 hours * Theophylline and other xanthines: 1 week * Parenteral or oral corticosteroids: 1 month * Patient has taken any non-permitted medication * Patient has received live-attenuated virus vaccination within two weeks prior to screening or during run-in (inactivated Influenza vaccination is acceptable if given \> 48 hours prior to Screening) * Known intolerance/hypersensitivity to β2-adrenergic agonists, propellant gases/excipients * Patient is pregnant or lactating female, or female at risk of pregnancy (i.e., not using adequate contraceptive method: surgical sterilization \[e.g., bilateral tubal ligation\], hormonal contraception \[implantable, patch, oral\], IUD, and double-barrier methods \[any double combination of: male or female condom with spermicidal gel, diaphragm, sponge, cervical cap\]). * Patient is mentally or legally incapacitated * Patient has participated in another investigational study within 30 days prior to screening * Abuse of 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 protocol outcome measurements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| FEV1 AUC0-24 standardized by time | on Day 15 (after 14 days of dosing) |
Secondary
| Measure | Time frame |
|---|---|
| FEV1(L) | 30 min, 1, 2 ,3, 4, 6, 10, 12, 14, 16, 22, 23, and 24 hrs post dose at Visit 2 at all treatment periods |
| blood pressure | at the beginning and end of each of the four 14-day treatment periods |
| heart rate | at the beginning and end of each of the four 14-day treatment periods |
| FEV1 percent change | 30 min, 1, 2 ,3, 4, 6, 10, 12, 14, 16, 22, 23, and 24 hrs post dose at Visit 2 at all treatment periods |
Countries
United States
Outcome results
None listed