Tiotropium Inhalation Capsules and Atrovent MDI Comparison Trial in Taiwan
Information source: Boehringer Ingelheim Pharmaceuticals
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pulmonary Disease, Chronic Obstructive
Intervention: tiotropium inhalation capsules (18 mcg once daily) (Drug); Atrovent MDI (2 puffs of 20 mcg(q.i.d.) in patients (Drug)
Phase: Phase 3
Sponsored by: Boehringer Ingelheim Pharmaceuticals
Official(s) and/or principal investigator(s):
Boehringer Ingelheim Study Coordinator, Study Chair, Affiliation: B.I. Taiwan Ltd.
The objective of this study is to compare the bronchodilator efficacy and safety of
tiotropium inhalation capsules (18 mcg once daily) and Atrovent MDI (2 puffs of 20 mcg
q. i.d.) in patients with chronic obstructive pulmonary disease (COPD)
Official title: Tiotropium Inhalation Capsules and Atrovent MDI Comparison Trial in Taiwan
Study design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: The primary endpoint is trough FEV1 response which is defined as change from baseline FEV1 (visit 2) and trough FEV1 at week 4 (visit 4)
Secondary outcome: FEV1 and FVC response at 2 hours post drug administration at on each pulmonary test day; Trough FVC response; Number of rescue medications; and Change from baseline in total score of patient evaluation questionnaire at week 4 (visit 4).
This is a randomized, double-blind, double-dummy, parallel group study to compare the
bronchodilator efficacy and safety of tiotropium inhalation capsules and Atrovent MDI in
patients with chronic obstructive pulmonary disease (COPD).
Following an initial screening visit, patients will enter a 2-week baseline period. Patients
who successfully complete this phase will be randomized into the double-blind portion of the
study in which they will receive tiotropium once daily (morning) or Atrovent four times
daily. Pulmonary function testing will be conducted just prior to the start of therapy at
Visit 2 (i. e. randomization visit after completion of the 2-week run-in period) and at 120
minutes post-dosing. Pulmonary function testing will be repeated at the same time intervals
at the end of therapy.
Null and alternative hypotheses The primary objective of this study was addressed by a
two-sided test at the 0. 05 level of significance of the null hypothesis that, in patients
with chronic obstructive pulmonary disease (COPD), the bronchodilator efficacy after one
month is no greater on tiotropium inhalation capsules (18mcg once daily) than on ATROVENT MDI
(2 puffs of 20 mcg q. i.d.), against the alternative hypothesis that the bronchodilator
efficacy is greater on tiotropium inhalation capsules (18 mcg once daily).
Trough FEV1 response will be analyzed. Peak FEV1, FVC trough and peak response, number of
Rescue Medication and change from baseline in total score of Patient Evaluation Questionnaire
will be analyzed. Change from baseline in each category score of Patient Evaluation
Questionnaire will be also analyzed.
Minimum age: 40 Years.
Maximum age: N/A.
1. COPD patients with an Forced Expiratory Volume in one second (FEV1)<= 65% of predicted
normal and FEV1 <= 70% of Forced Vital Capacity (FVC).
2. Male or female patients 40 years of age or older.
3. Patients must have a smoking history of more than 10 pack-years. A pack-year is
defined as the equivalent of smoking one pack of cigarettes per day for a year.
4. Patients must be able to perform pulmonary function tests as required in the
5. Patients must be able to inhale medication from the HandiHaler device and should have
a good technique of inhaling aerosol administered from an MDI..
6. All patients must sign an Informed Consent Form prior to participation in the trial
i. e., prior to pre-study washout of their usual pulmonary medications.
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
2. Patients with clinically significant abnormal baseline hematology, blood chemistry or
urinalysis, if the abnormality defines a disease listed as an exclusion criterion will
3. All patients with a SGOT and SGPT twice the upper normal limit, bilirubin 150% or
creatinine 125% of the upper normal limit will be excluded regardless of the clinical
condition. Repeat laboratory evaluation will not be conducted in these subjects.
4. Patients with a recent history (i. e. one year or less) of myocardial infarction.
5. Any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring
intervention or a change in drug therapy within the past year.
6. Patients with regular use of daytime oxygen therapy.
7. Patients with known active tuberculosis.
8. Patients with a history of cancer within the last five years. Patients with treated
basal cell carcinoma are allowed.
9. Patients with a history of life-threatening pulmonary obstruction, or a history of
cystic fibrosis or bronchiectasis.
10. A history of thoracotomy with pulmonary resection. Patients with a history of
thoracotomy for other reasons should be evaluated as per Exclusion 1.
11. Patients with an upper respiratory tract infection in the past 6 weeks prior to the
Screening Visit (=Visit 1) or during the baseline period of 2-weeks (run-in period).
12. Patients with known hypersensitivity to anticholinergic drugs, lactose or any other
component of the inhalation capsule delivery system.
13. Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction.
(Patients on BPH medications with minimum symptoms are permitted).
14. Patients with known narrow-angle glaucoma.
15. Patients who are being treated with cromolyn sodium or nedocromil sodium.
16. Patients who are being treated with antihistamines.
17. Patients using oral corticosteroid medication at unstable dosage (i. e. less than 6
weeks on a stable dose) or at a dose in excess of the equivalent 10 mg of prednisone
per day or 20 mg every other day.
18. Pregnant or nursing women or women of childbearing potential not using a medically
approved means of contraception (e. g. oral contraceptives, intrauterine devices, or
19. Patients with a history of asthma, allergic rhinitis or atopy or who have a blood
total eosinophil count bigger or equal 400 per ul (males) or bigger/equal 320 per ul
(females). A repeat eosinophil count will not be conducted in these patients.
20. Patients with a history and/or active alcohol or drug abuse.
21. Patients who have taken an investigational drug one month or six half-lives (whichever
is greater) prior to the Screening Visit (=Visit 1).
Locations and Contacts
Veterans General Hospital, Taipei 12217, Taiwan
National Taiwan University Hospital, Taipei 100, Taiwan
Tri-Service General Hospital, Taipei 114, Taiwan
Veterans General Hospital, Taichung 407, Taiwan
Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan
Starting date: September 2002
Ending date: October 2003
Last updated: January 12, 2007