Comparison of Tiotropium in the HandiHaler Versus the Respimat in Chronic Obstructive Pulmonary Disease
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: tiotropium 18 mcg; tiotropium 1.25 mcg (2 actuations/day); tiotropium 2.5 mcg (2 actuations/day)
Intervention description: HandiHaler; soft mist inhaler 2 actuations=2 puffs/day; soft mist inhaler (2 actuations=2 puffs/day)
Intervention MeSH terms: Tiotropium Bromide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 17183.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      Direct comparison studies of the tiotropium HandiHaler® 18 µg and Respimat® 5 µg formulations
      have been limited to 4-week crossover studies. Therefore, prospective data from a trial of
      adequate size and duration is required to establish that compared to tiotropium HandiHaler®,
      tiotropium Respimat® will have (a) similar effects on safety and (b) similar or superior
      effects on exacerbations.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients must sign an informed consent consistent with International Conference on
             Harmonization Good Clinical Practice (ICH-GCP) guidelines prior to participation in
             the trial, which includes medication washout and restrictions.

          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)

          4. All patients must have a diagnosis of COPD (P06-12085), and must meet the following
             criteria: Relatively stable airway obstruction with a post-bronchodilator FEV1 ≤ 70%
             of predicted normal and post-bronchodilator FEV1 / FVC ≤70%.

             Pulmonary function tests (PFTs) were conducted after the inhalation of 400 μg
             salbutamol / albuterol (preferred), however testing with either 200 μg
             salbutamol/albuterol or a combination of salbutamol / albuterol with ipratropium
             bromide (2 to 4 actuations) was acceptable. Other short-acting beta agonists, such as
             terbutaline, may have been used for the testing. The medication used for the testing
             was documented. Further, historical data from measurements within the past 6 months
             either at the site or at a referral site may have been used (see Section 6.2.1 of the
             CTP, located in Appendix 16.1.1). Subjects were not to have been randomized to the
             study without the availability of spirometry data at the actual study site.

             Eligibility for PFT sub-study: For subjects participating in the spirometry sub-study,
             historical data may not have been used for inclusion. These subjects must have
             qualified in the clinic at Visit 1 after performing a baseline measurement. These
             subjects performed a pre-dose PFT which was followed by the administration of 400 μg
             salbutamol / albuterol only (no other short-acting beta agonist was allowed), followed
             by a post-dose PFT for qualification.

          5. Able to inhale from the HandiHaler® and the Respimat® devices.

        Exclusion criteria:

          1. Significant diseases other than COPD. A significant disease is defined as a disease or
             condition which, in the opinion of the investigator, may put the patient at risk
             because of participation in the study or may influence the patients ability to
             participate in the study.

          2. Patients with a recent history (i.e., six months or less) of myocardial infarction.

          3. Patients with any unstable or life-threatening cardiac arrhythmia requiring
             intervention or change in drug therapy during the last year.

          4. Hospitalisation for cardiac failure (New York Heart Association (NYHA) Class III or
             IV) during the past year.

          5. Known active tuberculosis.

          6. Patients with a history of asthma, cystic fibrosis, clinically evident bronchiectasis,
             interstitial lung disease, or pulmonary thromboembolic disease.

          7. History of thoracotomy with pulmonary resection. Subjects with a history of
             thoracotomy for other reasons were to have been evaluated per exclusion criterion 1.

          8. Subject was planning to undergo lung transplant or lung volume reduction surgery
             (LVRS).

          9. Malignancy for which the subject had undergone resection, radiation, chemotherapy or
             biological treatments within the last 5 years. Subjects with treated basal cell
             carcinoma were allowed.

         10. Known respiratory infection or exacerbation of COPD in the 4 weeks prior to
             randomization.

         11. Known hypersensitivity to anticholinergic drugs, lactose, benzalkonium chloride (BAC),
             ethylenediaminetetraacetic acid (EDTA), or any other components of the HandiHaler® or
             Respimat® inhalation solution delivery system.

         12. Known moderate to severe renal impairment (as judged by the investigator).

         13. Known narrow angle glaucoma.

         14. Known significant symptomatic prostatic hyperplasia or bladder-neck obstruction.
             Subjects whose symptoms were controlled on treatment may have been included.

         15. Use of systemic corticosteroid medication at unstable doses (i.e., less than 6 weeks
             on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone per day.

         16. Pregnant or nursing women or women of childbearing potential not using a medically
             approved means of contraception for at least 3 months prior to and for the duration of
             the trial.

         17. Significant alcohol or drug abuse within the past 12 months.

         18. Subjects requiring the use of supplemental oxygen therapy for > 12 hours per day.

         19. Subjects who had completed a pulmonary rehabilitation program in the 6 weeks prior to
             the screening visit or subjects who were currently in a pulmonary rehabilitation
             program that was not maintained throughout the duration of the study.

         20. Subjects who had taken an investigational drug within 30 days prior to the Screening
             Visit.

         21. Previous participation (receipt of randomized treatment) in this study.

         22. Subjects who were currently participating in an interventional study.