Comparison of Tiotropium and Ipratropium in a Double-Blind, Double-dummy, Efficacy and Safety Study in Adults With COPD

Sponsor

Boehringer Ingelheim (Industry)

Overall Status

Completed

CT.gov ID

NCT00274040

Collaborator

(none)

141

Enrollment

Locations

Duration (Months)

7.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Comparison of 18 mcg of Tiotropium Inhalation Capsules and ipratropiumMetered Dose Inhaler (2 puffs of 20 mcg, four times daily) in a Double-Blind, Double-dummy, Efficacy and Safety Study in Adults with Chronic Obstructive Pulmonary Disease (COPD).

The objective of this study is to compare the bronchodilator efficacy and safety of tiotropium inhalation capsules (18 mcg once daily) and ipratropium MDI (2 puffs of 20 mcg q.i.d.) in patients with chronic obstructive pulmonary disease (COPD).

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Tiotropium Drug: Ipratropium	Phase 3

Detailed Description

This is a 2-treatment, randomized, double-blind, parallel design trial in adult patient with COPD.

Each dose of tiotropium or placebo will consist of one capsule self administered from the HandiHaler device once daily during the treatment period (tiotropium or placebo). Each dose will be taken at the same time each morning between 08:00 a.m. and 10:00 a.m.

Each dose of ipratropium MDI or placebo MDI will consist of 2 puffs; patients will inhale 2 puffs four times daily. The first dose will be taken at the same time each morning between 08:00 a.m. and 10:00 a.m.; subsequent doses will be taken at lunch, at dinner and when going to bed.

Study Hypothesis:

The null hypothesis is that there is no difference in mean response between tiotropium and ipratropium.

The alternative hypothesis is that there is a difference in mean response between tiotropium and ipratropium.

Comparison(s):

This is a multi-center, randomized, double-blind, double-dummy, parallel group trial to compare the bronchodilator efficacy and safety of Tiotropium (18 mcg once a day) and ipratropium Metered Dose Inhaler (2 puffs of 18 mcg four times a day).

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

A Comparison of 18 μg of Tiotropium Inhalation Capsules and Atrovent Metered Dose Inhaler (2 Puffs of 20 μg, 4 Times Daily) in a Double-Blind, Double-Dummy, Efficacy and Safety Study in Adults With Chronic Obstructive Pulmonary Disease (COPD).

Study Start Date :

Jul 1, 2002

Actual Primary Completion Date :

Mar 1, 2003

Actual Study Completion Date :

Mar 1, 2003

Outcome Measures

Primary Outcome Measures

Trough FEV1 response: change from baseline FEV1 (visit 2) to visit 4 trough FEV1 [4 weeks]

Secondary Outcome Measures

FEV1 (AUC0-3) response (change from baseline) for the 3 hours post drug administration [4 weeks]
Trough FVC response [4 weeks]
FVC (AUC0-3) response (as defined for FEV1) [4 weeks]
Patient questionnaire [4 weeks]
Daily PEFR [4 weeks]
Amount of rescue medication [4 weeks]
All adverse events [4 weeks]
Vital signs (pulse rate and blood pressure) [4 weeks]
Number of patients with abnormalities in routine blood chemistry, haematology and urinanalysis [4 weeks]
Changes from baseline in 12-lead electrocardiogram (ECG) [4 weeks]
Physical examination [4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

All patients must have a diagnosis of chronic obstructive pulmonary disease according to the following criteria:

Patients must have relatively stable airway obstruction with an FEV1 >= 65% of predicted normal and FEV1 70% of FVC. "Predicted normal values will be based on formulas as supplied by the individual study sites."

Male or female patients 40 years of age or older.
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.
Patients must be able to perform pulmonary function tests as required in the protocol.
Patients must be able to inhale medication from the HandiHaler device and should have a good technique of inhaling aerosol administered from an MDI.
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

Exclusion Criteria

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.
Patients with clinically significant abnormal baseline hematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion will be excluded.
All patients with a SGOT and SGPT twice the normal range, bilirubin 150% or creatinine 125% of the normal range will be excluded regardless of the clinical condition. Repeat laboratory evaluation will not be conducted in these subjects.
Patients with a recent history (i.e. one year or less) of myocardial infarction.
Patients with a recent history (i.e. three years or less) of heart failure or patients with any cardiac arrhythmia requiring drug therapy.
Patients with regular use of daytime oxygen therapy.
Patients with known active tuberculosis.
Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma are allowed.
Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
Patients who have undergone pulmonary resection or a thoracotomy for any reason.
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).
Patients with known hypersensitivity to anticholinergic drugs, lactose or any other component of the inhalation capsule delivery system or the MDI
Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction.
Patients with known narrow-angle glaucoma.
Patients who are being treated with cromolyn sodium or nedocromil sodium.
Patients who are being treated with antihistamines.
Patients using oral corticosteroid medication at unstable (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.
Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (e.g. oral contraceptives, intrauterine devices, or diaphragm).
Patients with a history of asthma, allergic rhinitis or atopy or who have a blood total eosinophil count 400>= per mcl (males) or 320>= per mcl (females). A repeat eosinophil count will not be conducted in these patients.
Patients with a history and/or active alcohol or drug abuse.
Patients who have taken an investigational drug one month or six half-lives (whichever is greater) prior to the Screening Visit (=Visit 1).

Contacts and Locations

Locations

	Site	City	Country
1	Chungnam National University Hospital	Daejeon	Korea, Republic of
2	Jeonbuk National University Hospital	Jeonju	Korea, Republic of
3	Jeonnam National University Hospital	Kwangju	Korea, Republic of
4	Pusan University Hospital	Pusan	Korea, Republic of
5	Chung-ang University Hospital	Seoul	Korea, Republic of
6	Hanyang University Hosital	Seoul	Korea, Republic of
7	Kangnam St. Mary's Hospital	Seoul	Korea, Republic of
8	Korea University Hospital	Seoul	Korea, Republic of
9	Kyoungbuk National University Hospital	Seoul	Korea, Republic of
10	Kyunghee University Hospital	Seoul	Korea, Republic of
11	National Medical Center	Seoul	Korea, Republic of
12	Samsung Seoul Hospital	Seoul	Korea, Republic of
13	Seoul Asan Hospital	Seoul	Korea, Republic of
14	Seoul National University Hospital	Seoul	Korea, Republic of
15	Shinchon Severence Hosp (Yonsei University Hosp)	Seoul	Korea, Republic of
16	St. Paul's Hospital, Dept. of Respiratory	Seoul	Korea, Republic of
17	Youngdong Sevarence Hospital (Yonsei University Hospital)	Seoul	Korea, Republic of
18	Wonju Christian Hospital (Yonsei University Hosp)	Wonju	Korea, Republic of