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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00239434
First received: October 14, 2005
Last updated: May 11, 2012
Last verified: May 2012
  Purpose

The objective of this study is to compare the bronchodilator efficacy and safety of once daily dosing of tiotropium inhalation capsules (18 ?g) and Atrovent? MDI (2 puffs of ipratropium bromide 20 ?g four times daily) in patients with chronic obstructive pulmonary disease.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: tiotropium inhalation powder capsule
Drug: ipratropium bromide Metered Dose Inhaler
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Comparison of 18 mg of Tiotropium Inhalation Capsules Once Daily and Atrovent Metered Dose Inhaler (2 Puffs of 20 mg, Four Times Daily) in a Double-Blind, Double-dummy, Efficacy and Safety Study in Adults With Chronic Obstructive Pulmonary Disease (COPD).

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Trough FEV1 response: change from baseline trough FEV1 (visit 2) at visit 4

Secondary Outcome Measures:
  • Trough FEV1 response at visit 3 Average FEV1 (AUC0-3) response (change from baseline) for the 3 hours post drug administration Trough FVC response Average FVC (AUC0-3) response (as defined for FEV1) 5. Amount of rescue medication 6. Patient questionnaire

Estimated Enrollment: 200
Study Start Date: June 2003
Estimated Study Completion Date: March 2004
Detailed Description:

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 for 4 weeks. Pulmonary function testing will be conducted just prior (i.e. 5 minutes before) to the start of therapy at Visit 2 (i.e. randomization visit after completion of the 2-week run-in period) and at 30, 60, 120 and 180 minutes post-dosing. Pulmonary function testing will be repeated at the same time intervals after 14 days of therapy (visit 3) and at the end of therapy.

Those patients taking theophylline, will be questioned about their last theophylline intake in order to ensure adherence to the washout requirements.

Vital signs will be measured in conjunction with the pulmonary function tests. Adverse events will be recorded throughout the entire run-in and treatment period.

Study Hypothesis:

The null hypothesis is that there is no difference in mean response between tiotropium and Atrovent. The alternative hypothesis is that there is a difference in mean response between tiotropium and Atrovent.

Comparison(s):

The primary pulmonary function variable will be FEV1 (Forced Expiratory Volume in one second) and trough FEV1 response at the end of the four week treatment period, i.e. visit 4, will be the primary efficacy endpoint.

Trough FEV1 is defined as FEV1 at the end of the dosing interval (for tiotropium at approximately 24 hours post treatment administration). On test days (Visits 3 and 4) it is measured by the PFT just prior to dosing. Trough FEV1 response is defined as change from baseline in trough FEV1. Baseline FEV1 is defined as FEV1 measured just prior to first dosing in the morning of randomization visit (Visit 2).

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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 the following formula. Males: FEV1 pred.(L) = height2(m) x (-0.016 x age(year) + 1.823) Females: FEV1 pred.(L) = height2(m) x (-0.012 x age(year) + 1.4427)

  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 protocol.
  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.

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 clinically significant abnormal baseline hematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion will be excluded.
  3. 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.
  4. Patients with a recent history (i.e. one year or less) of myocardial infarction.
  5. Patients with a recent history (i.e. three years or less) of heart failure or patients with any cardiac arrhythmia requiring drug therapy.
  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. Patients who have undergone pulmonary resection.
  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 or the MDI.
  13. Patients with known symptomatic prostatic hyperplasia or bladder neck obstruction.
  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 (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 diaphragm).
  19. Patients with a history of asthma, allergic rhinitis or atopy or who have a blood total eosinophil count >= 400 per µl (males) or >= 320 per µl (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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00239434

Locations
China
Peking Union Medical College Hospital
Beijing, China, 100730
People Hospital of Beijing University
Beijing, China, 100044
1st Hospital of Guangzhou Medical College
Guangzhou, China, 510120
Shanghai 1st People Hospital
Shanghai, China, 200080
Zhongshan Hospital of Fudan University
Shanghai, China, 200032
1st Hospital of Chinese Medical University
Shenyang, China, 110001
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator Boehringer Ingelheim Shanghai
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00239434     History of Changes
Other Study ID Numbers: 205.245
Study First Received: October 14, 2005
Last Updated: May 11, 2012
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Ipratropium
Tiotropium
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Parasympatholytics

ClinicalTrials.gov processed this record on August 27, 2014