Respimat® Combivent Trial in Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00400153
First received: November 15, 2006
Last updated: May 18, 2012
Last verified: May 2012
  Purpose

The primary objective of this study is to compare the effect of ipratropium bromide/salbutamol inhalation spray combination administered by the Respimat® inhaler (20 mcg/100 mcg), ipratropium bromide inhalation spray administered by the Respimat® inhaler (20 mcg), and COMBIVENT® MDI administered q.i.d on FEV1 at intervals over a treatment period of 12 weeks in patients with COPD. Specifically, non-inferiority of Combivent Respimat® to COMBIVENT® MDI in FEV1 AUC from 0 to 6 hours , superiority of Combivent Respimat® to Atrovent Respimat® monotherapy in FEV1 AUC from 0 to 4 hours, and non-inferiority of Combivent Respimat® to Atrovent Respimat® monotherapy in FEV1 AUC from 4 to 6 hours will be analyzed. In addition, steady state pharmacokinetics over one dosing interval following 4 weeks of therapy will be characterized in a subgroup of patients.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Atrovent Respimat (20 mcg) plus placebo COMBIVENT MDI
Drug: COMBIVENT MDI (36/206 mcg ) plus placebo Combivent Respimat
Drug: Combivent Respimat (20 mcg/100 mcg) plus placebo COMBIVENT MDI
Phase 3

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Safety and Efficacy of Combivent Respimat in Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • FEV1 AUC0-6 at Day 85 [ Time Frame: Before drug administration to 6 hours after drug administration on Day 85 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 85

  • FEV1 AUC0-4 at Day 85 [ Time Frame: Before drug administration to 4 hours after drug administration on Day 85 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 85

  • FEV1 AUC4-6 at Day 85 [ Time Frame: Between 4 hours and 6 hours after drug administration on Day 85 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 85


Secondary Outcome Measures:
  • FEV1 AUC0-6 at Day 1 [ Time Frame: Before drug administration to 6 hours after drug administration on Day 1 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 1

  • FEV1 AUC0-6 at Day 29 [ Time Frame: Before drug administration to 6 hours after drug administration on Day 29 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 29

  • FEV1 AUC0-6 at Day 57 [ Time Frame: Before drug administration to 6 hours after drug administration on Day 57 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 57

  • FEV1 AUC0-4 at Day 1 [ Time Frame: Before drug administration to 4 hours after drug administration on Day 1 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 1

  • FEV1 AUC0-4 at Day 29 [ Time Frame: Before drug administration to 4 hours after drug administration on Day 29 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 29

  • FEV1 AUC0-4 at Day 57 [ Time Frame: Before drug administration to 4 hours after drug administration on Day 57 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 57

  • FEV1 AUC4-6 at Day 1 [ Time Frame: Between 4 hours and 6 hours after drug administration on Day 1 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 1

  • FEV1 AUC4-6 at Day 29 [ Time Frame: Between 4 hours and 6 hours after drug administration on Day 29 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 29

  • FEV1 AUC4-6 at Day 57 [ Time Frame: Between 4 hours and 6 hours after drug administration on Day 57 ]
    Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 57

  • Peak FEV1 Response at Day 1 [ Time Frame: Within the first 2-hour post-treatment interval on Day 1 ]
    Maximum change in recorded FEV1 value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 1

  • Peak FEV1 Response at Day 29 [ Time Frame: Within the first 2-hour post-treatment interval on Day 29 ]
    Maximum change in recorded FEV1 value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 29

  • Peak FEV1 Response at Day 57 [ Time Frame: Within the first 2-hour post-treatment interval on Day 57 ]
    Maximum change in recorded FEV1 value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 57

  • Peak FEV1 Response at Day 85 [ Time Frame: Within the first 2-hour post-treatment interval on Day 85 ]
    Maximum change in recorded FEV1 value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 85

  • Time to Onset of Therapeutic FEV1 Response at Day 1 [ Time Frame: Within the first 2-hour post-treatment interval at Day 1 ]
    Achievement of recorded FEV1 measurement of at least 1.15 times of the corresponding test-day baseline value at any time during the first 2 hours of observation after drug administration at Day 1

  • Time to Onset of Therapeutic FEV1 Response at Day 29 [ Time Frame: Within the first 2-hour post-treatment interval at Day 29 ]
    Achievement of recorded FEV1 measurement of at least 1.15 times of the corresponding test-day baseline value at any time during the first 2 hours of observation after drug administration at Day 29

  • Time to Onset of Therapeutic FEV1 Response at Day 57 [ Time Frame: Within the first 2-hour post-treatment interval at Day 57 ]
    Achievement of recorded FEV1 measurement of at least 1.15 times of the corresponding test-day baseline value at any time during the first 2 hours of observation after drug administration at Day 57

  • Time to Onset of Therapeutic FEV1 Response at Day 85 [ Time Frame: Within the first 2-hour post-treatment interval at Day 85 ]
    Achievement of recorded FEV1 measurement of at least 1.15 times of the corresponding test-day baseline value at any time during the first 2 hours of observation after drug administration at Day 85

  • Duration of Therapeutic FEV1 Response at Day 1 [ Time Frame: During the 6-hour observation period after drug administration at Day 1 ]
    The time interval between the onset and the the termination of a therapeutic FEV1 response (at least 1.15 times the corresponding test-day baseline value) during the 6-hour observation period at Day 1

  • Duration of Therapeutic FEV1 Response at Day 29 [ Time Frame: During the 6-hour observation period after drug administration at Day 29 ]
    The time interval between the onset and the the termination of a therapeutic FEV1 response (at least 1.15 times the corresponding test-day baseline value) during the 6-hour observation period at Day 29

  • Duration of Therapeutic FEV1 Response at Day 57 [ Time Frame: During the 6-hour observation period after drug administration at Day 57 ]
    The time interval between the onset and the the termination of a therapeutic FEV1 response (at least 1.15 times the corresponding test-day baseline value) during the 6-hour observation period at Day 57

  • Duration of Therapeutic FEV1 Response at Day 85 [ Time Frame: During the 6-hour observation period after drug administration at Day 85 ]
    The time interval between the onset and the the termination of a therapeutic FEV1 response (at least 1.15 times the corresponding test-day baseline value) during the 6-hour observation period at Day 85

  • Time to Peak FEV1 Response at Day 1 [ Time Frame: Within the 6-hour post-treatment observation period at Day 1 ]
    The first time point at which the maximum change in recorded FEV1 data from the corresponding test-day baseline occurred during the 6-hours observation period after drug administration at Day 1

  • Time to Peak FEV1 Response at Day 29 [ Time Frame: Within the 6-hour post-treatment observation period at Day 29 ]
    The first time point at which the maximum change in recorded FEV1 data from the corresponding test-day baseline occurred during the 6-hours observation period after drug administration at Day 29

  • Time to Peak FEV1 Response at Day 57 [ Time Frame: Within the 6-hour post-treatment observation period at Day 57 ]
    The first time point at which the maximum change in recorded FEV1 data from the corresponding test-day baseline occurred during the 6-hours observation period after drug administration at Day 57

  • Time to Peak FEV1 Response at Day 85 [ Time Frame: Within the 6-hour post-treatment observation period at Day 85 ]
    The first time point at which the maximum change in recorded FEV1 data from the corresponding test-day baseline occurred during the 6-hours observation period after drug administration at Day 85

  • FVC AUC0-6 at Day 1 [ Time Frame: Before drug administration to 6 hours after drug administration at Day 1 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 1

  • FVC AUC0-6 at Day 29 [ Time Frame: Before drug administration to 6 hours after drug administration at Day 29 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 29

  • FVC AUC0-6 at Day 57 [ Time Frame: Before drug administration to 6 hours after drug administration on Day 57 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 57

  • FVC AUC0-6 at Day 85 [ Time Frame: Before drug administration to 6 hours after drug administration on Day 85 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 85

  • FVC AUC0-4 at Day 1 [ Time Frame: Before drug administration to 4 hours after drug administration on Day 1 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 1

  • FVC AUC0-4 at Day 29 [ Time Frame: Before drug administration to 4 hours after drug administration on Day 29 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 29

  • FVC AUC0-4 at Day 57 [ Time Frame: Before drug administration to 4 hours after drug administration on Day 57 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 57

  • FVC AUC0-4 at Day 85 [ Time Frame: Before drug administration to 4 hours after drug administration on Day 85 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 85

  • FVC AUC4-6 at Day 1 [ Time Frame: Between 4 hours and 6 hours after drug administration on Day 1 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 1

  • FVC AUC4-6 at Day 29 [ Time Frame: Between 4 hours and 6 hours after drug administration on Day 29 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 29

  • FVC AUC4-6 at Day 57 [ Time Frame: Between 4 hours and 6 hours after drug administration on Day 57 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 57

  • FVC AUC4-6 at Day 85 [ Time Frame: Between 4 hours and 6 hours after drug administration on Day 85 ]
    Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 85

  • Peak FVC Response at Day 1 [ Time Frame: Within the first 2-hour post-treatment interval at Day 1 ]
    Maximum change in recorded FVC value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 1

  • Peak FVC Response at Day 29 [ Time Frame: Within the first 2-hour post-treatment interval at Day 29 ]
    Maximum change in recorded FVC value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 29

  • Peak FVC Response at Day 57 [ Time Frame: Within the first 2-hour post-treatment interval at Day 57 ]
    Maximum change in recorded FVC value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 57

  • Peak FVC Response at Day 85 [ Time Frame: Within the first 2-hour post-treatment interval at Day 85 ]
    Maximum change in recorded FVC value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 85

  • Rescue Medication Use on Pulmonary Test Day 1 [ Time Frame: During the 6-hour pulmonary function testing after drug administration on Day 1 ]
    Number of patients used rescue medication during the 6-hour pulmonary function testing after drug administration on Day 1

  • Rescue Medication Use on Pulmonary Test Day 29 [ Time Frame: During the 6-hour pulmonary function testing after drug administration on Day 29 ]
    Number of patients used rescue medication during the 6-hour pulmonary function testing after drug administration on Day 29

  • Rescue Medication Use on Pulmonary Test Day 57 [ Time Frame: During the 6-hour pulmonary function testing after drug administration on Day 57 ]
    Number of patients used rescue medication during the 6-hour pulmonary function testing after drug administration on Day 57

  • Rescue Medication Use on Pulmonary Test Day 85 [ Time Frame: During the 6-hour pulmonary function testing after drug administration on Day 85 ]
    Number of patients used rescue medication during the 6-hour pulmonary function testing after drug administration on Day 85

  • Night-time Rescue Medication Use [ Time Frame: During the 2-week baseline washout period and the 12-week treatment period ]
    The mean number of puffs of rescue medication used during the night-time per week during the entire study (including baseline and on-treatment period)

  • Daytime Rescue Medication Use [ Time Frame: During the 2-week baseline washout period and the 12-week treatment period ]
    The mean number of puffs of rescue medication used during the daytime per week during the entire study (including baseline and on-treatment period)

  • Night-time Symptom Score [ Time Frame: During the 2-week baseline washout period and the 12-week treatment period ]
    The weekly mean night-time symptom score per week during the entire study (including baseline and on-treatment period)

  • Daytime Symptom Score [ Time Frame: During the 2-week baseline washout period and the 12-week treatment period ]
    The weekly mean daytime symptom score per week during the entire study (including baseline and on-treatment period)

  • Trough Peak Expiratory Flow Rate (PEFR) [ Time Frame: During the 2-week baseline washout period and the 12-week treatment period and PEFR taken before administration of study medication ]
    The weekly mean trough PEFR during the entire study (including baseline and on-treatment period)

  • Trough PEFR [ Time Frame: During the 2-week baseline washout period and the 12-week treatment period and PEFR taken before administration of study medication ]
    The weekly mean trough PEFR during the entire study (including baseline and on-treatment period)

  • Physician's Global Evaluation Score on Pulmonary Function Testing Day 29 [ Time Frame: Prior to pulmonary function test on Day 29 ]
    Physician's Global Evaluation score is based on the need for concomitant medication, number and severity of exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, etc.

  • Physician's Global Evaluation Score on Pulmonary Function Testing Day 57 [ Time Frame: Prior to pulmonary function test on Day 57 ]
    Physician's Global Evaluation score is based on the need for concomitant medication, number and severity of exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, etc.

  • Physician's Global Evaluation Score on Pulmonary Function Testing Day 85 [ Time Frame: Prior to pulmonary function test on Day 85 ]
    Physician's Global Evaluation score is based on the need for concomitant medication, number and severity of exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, etc.

  • Chronic Obstructive Pulmonary Disease (COPD) Excerbation During the On-treatment Period [ Time Frame: During the 12-week on-treatment period ]
    COPD excerbation is defined as an increase or new onset of more than one of the following respiratory symptoms (cough, sputum, sputum purulence, wheezing, dyspnea, and chest tightness) having a duration of three or more days requiring treatment with an antibiotic and/or systemic steroids with or without hospital admission.

  • COPD Excerbation During the On-treatment Period [ Time Frame: During the 12-week on-treatment period ]
    COPD excerbation is defined as an increase or new onset of more than one of the following respiratory symptoms (cough, sputum, sputum purulence, wheezing, dyspnea, and chest tightness) having a duration of three or more days requiring treatment with an antibiotic and/or systemic steroids with or without hospital admission.


Enrollment: 1480
Study Start Date: November 2006
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: COMBIVENT Respimat 20/100 mcg Drug: Combivent Respimat (20 mcg/100 mcg) plus placebo COMBIVENT MDI
Experimental: COMBIVENT CFC-MDI 36/206 mcg Drug: COMBIVENT MDI (36/206 mcg ) plus placebo Combivent Respimat
Experimental: Ipratropium Respimat 20 mcg Drug: Atrovent Respimat (20 mcg) plus placebo COMBIVENT MDI

  Eligibility

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

Inclusion Criteria:

Outpatients of either sex, 40 years or older, with a diagnosis of COPD (FEV1 65% predicted normal and FEV1/FVC 70%).

Exclusion Criteria:

Patients with significant diseases other than COPD that 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, with a history of asthma or allergic rhinitis, who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy or using oral corticosteroid me dication at unstable doses (i.e., less than 6 weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day will be excluded.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00400153

  Show 180 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00400153     History of Changes
Other Study ID Numbers: 1012.56
Study First Received: November 15, 2006
Results First Received: April 3, 2009
Last Updated: May 18, 2012
Health Authority: Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine)
New Zealand: Multicentre Ethics Committee/Medsafe
United States: Food and Drug Administration
France: AFSSAPS
Greece: National Organization for Medicines (EOF) National Ethics Committee
Argentina: A.N.M.A.T. (Administración Nacional de Medicamentos, Alimentos y Tecnología)
Taiwan: Department of Health, Executive Yuan, Taiwan
Korea, Republic of: Korea Food and Drug Administration
Turkey: Ministry of Health Central Ethics Committee
Great Britain: MHRA
South Africa: MCC (Medicines Control Council)

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Ipratropium
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

ClinicalTrials.gov processed this record on April 22, 2014