Clinical trial NCT00640484: Confirmatory Dose Finding Study of 2 Dosages of CHF 4226 pMDI (Carmoterol) in Patients With COPD
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2008-03-21
Enrollment: 57
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: FEV1 AUC0-24 standardized by time
timeFrame: on Day 15 (after 14 days of dosing)
Secondary outcomes:
measure: FEV1(L)
timeFrame: 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
measure: blood pressure
timeFrame: at the beginning and end of each of the four 14-day treatment periods
measure: heart rate
timeFrame: at the beginning and end of each of the four 14-day treatment periods
measure: FEV1 percent change
timeFrame: 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
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Horizon Clinical Research Associates, PLLC
state: Arizona
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Los Angeles
country: United States
facility: UCLA David Geffen School of Medicine
state: California
city: DeLand
country: United States
facility: University Clinical Research - DeLand, LLC
state: Florida
city: Austell
country: United States
facility: Pulmonary Medicine and Critical Care
state: Georgia
city: Normal
country: United States
facility: Sneeze, Wheeze & Itch Associates, LLC
state: Illinois
city: Madisonville
country: United States
facility: Commonwealth BioMedical Research
state: Kentucky
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon, PC
state: Oregon
city: Portland
country: United States
facility: Asthma Allergy Associates
state: Oregon
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Sugar Land
country: United States
facility: Reichman Associates
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of California, Los Angeles
name: Donald P. Tashkin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chiesi Farmaceutici S.p.A.
name: Steven E. Linberg, PhD
role: STUDY_DIRECTOR
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