Comparison of Tiotropium in the HandiHaler Versus the Respimat in Chronic Obstructive Pulmonary Disease

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Drug: tiotropium 2.5 mcg (2 actuations/day); Drug: tiotropium 18 mcg; Drug: tiotropium 1.25 mcg (2 actuations/day)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01126437

205.452

2009-015713-51 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 17,183 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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17,183 participants in 3 patient groups

tiotropium 2.5 mcg and placebo

Experimental group

Description:

Patients receive one of the active tiotropium arms daily

Treatment:

Drug: tiotropium 1.25 mcg (2 actuations/day)

tiotropium 18 mcg and placebo

Active Comparator group

Description:

Patients receive one of the active tiotropium arms daily

Treatment:

Drug: tiotropium 18 mcg

tiotropium 5 mcg and placebo

Experimental group

Description:

Patients receive one of the active tiotropium arms daily

Treatment:

Drug: tiotropium 2.5 mcg (2 actuations/day)