Overview

Pharmacokinetics and Safety Comparison of Tiotropium Inhalation Powder Administered as the Bromide Salt From Hard Polyethylene Capsule Via the HandiHaler® 2 and Spiriva® HandiHaler® in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Status:
Completed
Trial end date:
1969-12-31
Target enrollment:
0
Participant gender:
All
Summary
The primary objective of this trial was to establish non-inferiority of lung function response to tiotropium 10 μg, formulated as inhalation powder in the polyethylene hard capsule and delivered via the HandiHaler® 2, compared to tiotropium 18 μg, formulated as inhalation powder in the hard gelatine capsule and delivered via the HandiHaler® (Spiriva®) following single dose inhalation in patients with COPD. A hard polyethylene (PE) capsule with half the strength (tiotropium 5 μg) was included to investigate a dose ordering effect. The secondary objectives were to characterize the pharmacokinetics of tiotropium inhalation powder hard PE capsule (delivered via HandiHaler® 2) and tiotropium inhalation powder hard gelatine capsule (delivered via HandiHaler®) and to compare the safety of the two pharmaceutical formulations.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Boehringer Ingelheim
Treatments:
Bromides
Tiotropium Bromide
Criteria
Inclusion Criteria:

1. All patients must sign an informed consent consistent with International Conference on
Harmonization Good Clinical Practice (ICH-GCP) guidelines and local legislations prior
to any study-related procedures, which includes medication washout and restrictions

2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must
meet the following spirometric criteria:

Patients must have relatively stable* airway obstruction with a pre-dose FEV1 <= 60%
of predicted normal and FEV1 <= 70% of FVC at Visits 1 and 2.

- * The randomization of patients with any respiratory infection or COPD
exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the
baseline period should be postponed. Patients may be randomized 6 weeks following
recovery from the infection or exacerbation

3. At Visit 1, patients must demonstrate an improvement in FEV1 of >= 12% over the
baseline FEV1 value 45 minutes after inhalation of 4 puffs of 20 µg ipratropium
bromide (Atrovent® MDI)

4. Male or female patients 40 years of age or older

5. Patients must be current or ex-smokers with a smoking history of more than 10
pack-years (Patients who had never smoked cigarettes had to be excluded)

6. Patients must be able to perform technically acceptable pulmonary function tests
during the study period as required in the protocol

7. Patients must be able to inhale medication in a competent manner from the HandiHaler®
2 and the HandiHaler® devices

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., six months or less) of myocardial infarction

3. Patients who have been hospitalized for heart failure (NYHA class III or IV) within
the past year

4. Patients with any unstable or life threatening cardiac arrhythmia or cardiac
arrhythmia requiring intervention or a change in drug therapy within the past year

5. Patients with malignancy for which the patient has undergone resection, radiation
therapy or chemotherapy within the last five years. Patients with treated basal cell
carcinoma are allowed

6. Patients with a history of asthma, allergic rhinitis or atopy or who have a total
blood eosinophil count ≥600/mm3. A repeat eosinophil count will not be conducted in
these patients

7. Patients with a history of life threatening pulmonary obstruction, or a history of
cystic fibrosis or clinically evident bronchiectasis

8. Patients with known active tuberculosis

9. Patients with significant alcohol or drug abuse within the past two years

10. Patients who have undergone thoracotomy with pulmonary resection. Patients with a
history of thoracotomy for other reasons should be evaluated as per exclusion
criterion No. 1

11. Patients who have completed a pulmonary rehabilitation program in the six weeks prior
to the Screening Visit (Visit 1) or patients who are currently in a pulmonary
rehabilitation program that will not be maintained throughout the duration of the
study

12. Patients who regularly use daytime oxygen therapy for more than one hour per day and
in the investigator's opinion will be unable to abstain from the use of oxygen therapy

13. Patients who are being treated with antihistamines (H1 receptor antagonists),
antileukotrienes or leukotriene receptor antagonists for asthma or excluded allergic
conditions. See exclusion criterion No 6

14. Patients who are being treated with cromolyn sodium or nedocromil sodium

15. Patients using oral corticosteroid medication at unstable doses (i.e., less than six
weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone
per day or 20 mg every other day

16. Patients with known hypersensitivity to anticholinergic drugs, lactose or any other
components of the inhalation capsule delivery system (Spiriva® HandiHaler®; tiotropium
HandiHaler 2)

17. Pregnant or nursing women or women of childbearing potential not using a medically
approved means of contraception for the previous three months (i.e. oral
contraceptives, intrauterine devices, diaphragm or subdermal implants, e.g.:
Norplant®)

18. Patients who have taken an investigational drug within one month or six half lives
(whichever is greater) prior to Visit 1

19. Patients who have been treated with oral beta-adrenergics within one month prior to
Visit 1 or during the run-in period

20. Patients who have been treated with theophylline preparations within one month prior
to Visit 1 or during the run-in period

21. Patients who have been treated with the long-acting anticholinergic tiotropium
(Spiriva®) within one month prior to Visit 1 or during the run-in period

22. Patients with any respiratory infections in the six weeks prior to the Screening Visit
(Visit 1) or during the run-in period. In the case of a respiratory infection during
the run-in period the latter may be extended up to six weeks

23. Patients who are currently participating in another study23. The randomisation of
patients with any respiratory infection or COPD exacerbation in the six weeks prior to
the Screening Visit (Visit 1) or during the baseline period should be postponed.
Patients may be randomised six weeks following recovery from the infection or
exacerbation