Combivent Respimat 1-year Safety Study in Patients With Chronic Obstructive Pulmonary Disease
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Combivent CFC-MDI; Combivent Respimat 20/100 mcg; Atrovent HFA 42 mcg + Albuterol HFA 200 mcg
Intervention description: 36/206 mcg Four times a day (QID); Open label randomized parallel; Open label randomized parallel
Intervention MeSH terms: Albuterol; Ipratropium
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 470.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate long-term safety and patient acceptability
      of COMBIVENT RESPIMAT Inhalation Spray as compared to the COMBIVENT Inhalation Aerosol
      Chlorofluorocarbon-Metered Dose Inhaler (CFC-MDI) and the free combination of ATROVENT
      Hydrofluoroalkane (HFA) and albuterol Hydrofluoroalkane (HFA) inhalation aerosols.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients must sign an informed consent consistent with International Conference on
             Harmonization (ICH) Good Clinical Practice (GCP) guidelines prior to participation in
             the trial.

          2. Male or female patients 40 years of age or older.

          3. Patients must be current or ex-smokers with a smoking history of 10 pack-years.
             (Patients who have never smoked cigarettes must be excluded) Pack Years = Number of
             cigarettes/day x years of smoking 20 cigarettes/pack

          4. All patients must have a diagnosis of Chronic Obstructive Pulmonary Disease (COPD)
             (P95-4381), and must meet the following spirometric criteria at Visit 1:Relatively
             stable, moderate to severe airway obstruction with a post-bronchodilator Forced
             Expiratory Volume in one second (FEV1) < 80% of predicted normal and FEV1/Forced Vital
             Capacity (FVC) < 70%. Spirometry should be done at baseline and approximately 1/2 hour
             following 4 inhalations of albuterol. Predicted normal values will be calculated
             according to European Coal and Steel Community (ECSC), European Community for Coal and
             Steel (ECCS), (R94-1408). For Height measured in inches Males: FEV1 predicted (L) =
             4.30 x [height (inches) / 39.37]-0.029 x age (yrs) - 2.49 Females: FEV1 predicted (L)
             = 3.95 x [height (inches) / 39.37]-0.025 x age (yrs) - 2.60 For Height measured in
             meters Males: FEV1 predicted (L) = 4.30 x [height (meters)] - 0.029 x age (years)
             -2.49 Females: FEV1 predicted (L) = 3.95 x [height (meters)] - 0.025 x age (years) -
             2.60

          5. Patients must be able to perform all study related procedures and maintain study
             records during the study period as required in the protocol.

          6. Patients must be able to inhale medication in a competent manner from the RESPIMAT
             inhaler and from a metered dose inhaler (MDI).

        Exclusion criteria:

          1. Patients with significant diseases other than COPD will be excluded. A significant
             disease is defined as a disease which in the opinion of the investigator may either
             put the patient at risk because of participation in the study or a disease which may
             influence the results of the study or the patient's ability to participate in the
             study.

          2. Patients with a recent history (i.e., one year or less) of myocardial infarction.

          3. Patients who have been hospitalized or being treated for heart failure within the past
             year.

          4. Patients with clinically unstable or life-threatening cardiac arrhythmia requiring
             intervention or change in drug therapy within the past year.

          5. Patients with a malignancy for which patient has undergone resection, radiation
             therapy or chemotherapy within last five years (patients with fully cured squamous
             cell or treated basal cell carcinoma are allowed).

          6. Patients with a history of life-threatening pulmonary obstruction, or a history of
             cystic fibrosis or clinically evident bronchiectasis.

          7. Patients who have undergone thoracotomy with pulmonary resection. Patients with a
             history of a thoracotomy for other reasons should be evaluated as per exclusion
             criterion No. 1.

          8. Patients with a current diagnosis of asthma.

          9. Patients with a history of significant alcohol or drug abuse.

         10. Patients with known active tuberculosis.

         11. Patients using beta blocker medications are excluded. Cardioselective beta blockers
             are allowed with caution. Beta blocker eye medications for treatment of non-narrow
             angle glaucoma are allowed.

         12. Patients who regularly use daytime oxygen therapy for more than 1 hour per day
             Continuous Positive Airway Pressure (CPAP for sleep apnea is allowed).

         13. Patients using oral corticosteroid medication at a dose in excess of the equivalent of
             10 mg of prednisone per day or 20 mg every other day, except as required for treatment
             of exacerbation during the study.

         14. Pregnant or nursing women.

         15. Women of childbearing potential not using a medically approved means of contraception
             (i.e., oral or injectable contraceptives, intrauterine devices or diaphragm with
             spermicide, or transdermal hormonal patches). Abstinence will not be accepted as a
             medically approved means of contraception. Female patients will be considered to be of
             childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal
             ligation, or post-menopausal for at least two years.

         16. Patients with known hypersensitivity to anticholinergic drugs, any other component of
             the ipratropium bromide/albuterol RESPIMAT solution including Benzalkonium chloride
             (BAC) and Ethylenediaminetetraacetic acid (EDTA) or the ipratropium bromide/albuterol
             Chlorofluorocarbons (CFC) MDI or Hydrofluoroalkane (HFA) components.

         17. Previous participation in this study. (The patient cannot re-enroll into this study.)

         18. Patients who are currently participating in another interventional study.

         19. Patients who have taken an investigational drug within 1 month or 6 half lives
             (whichever is greater) prior to screening.

         20. Patients currently in any pulmonary rehabilitation program or scheduled to participate
             in any such program during the study period.