Official Title: “Evaluation of the Effect of 2 Weeks Treatment With CHF 4226 pMDI 2µg and 4µg, Given Once Daily in the Morning, on 24-Hour FEV1 in Patients With COPD”

The purpose of this study is to confirm the dose of CHF 4226 which should be given once a day to patients with COPD in order for the effect to last for 24 hours.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Crossover Assignment, Efficacy Study

Study Primary Completion Date: November 2008

Intervention(s) in this Clinical Trial

• Drug: carmoterol
  • carmoterol 2 μg once a day, in the morning (1 puff of carmoterol 2 μg + 1 puff of placebo pMDI)
• Drug: carmoterol
  • carmoterol 4 μg once a day, in the morning (1 puff of carmoterol 2 µg + 1 puff of carmoterol 2µg)
• Drug: placebo
  • placebo once a day, in the morning (1 puff of placebo pMDI + 1 puff of placebo pMDI)
• Drug: salmeterol
  • Salmeterol 50 μg twice daily, in the morning and in the evening (1 blister of Serevent Diskus BID)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • carmoterol 2 μg once a day, in the morning
• Experimental: B
  • carmoterol 4 μg once a day, in the morning
• Placebo Comparator: C
  • placebo once a day, in the morning
• Active Comparator: D
  • salmeterol 50 μg twice daily, in the morning and in the evening

Primary Measures

• FEV1 AUC0-24 standardized by time
  • Time Frame: on Day 15 (after 14 days of dosing)
    Safety Issue?: No

Secondary Measures

• Pulmonary Function Tests
  • Time Frame: 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
    Safety Issue?: No
• Vital Signs
  • Time Frame: at each visit
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Chiesi Farmaceutici S.p.A.

Overall Clinical Trial Officials and Contacts

Donald P. Tashkin, MD Principal Investigator David Geffen School of Medicine at UCLA  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00640484

Study ID Number: CCD-0706-PR-0026

ClinicalTrials.gov Identifier: NCT00640484

Health Authority: United States: Food and Drug Administration