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Ipratropium Bromide/Salbutamol Delivered by the Respimat® Inhaler Compared to Ipratropium Bromide Respimat®, COMBIVENT® Inhalation Aerosol and Placebo in Adults With Chronic Obstructive Pulmonary Disease

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ipratropium bromide / Salbutamol
Placebo Inhalation solution
Ipratropium bromide
COMBIVENT Inhalation Aerosol
Placebo Inhalation Aerosol
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • All patients must have a diagnosis of COPD and the following spirometric criteria:

    • Visit 1 (Screening) and Visit 2: Patients must have relatively stable, moderate to severe airway obstruction with an FEV1 ≤65% of predicted normal and FEV1 ≤70% of FVC
  • Male or female patients 40 years of age or older
  • Patients must have a smoking history of more than ten pack-years. A pack-year is defined as the equivalent of smoking one pack of 20 cigarettes per day for a year
  • Patients must be able to perform pulmonary function tests and maintain records during the study period as required in the protocol
  • Patients must be able to be trained in the proper use of an MDI (metered dose inhaler) and the Respimat® inhaler
  • All patients must sign an Informed Consent Form prior to participation in the trial

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 relevant abnormal baseline hematology, blood chemistry or urinalysis. If the abnormality defines a disease listed as an exclusion criterion, the patient is excluded
  • All patients with a SGOT (serum glutamic oxaloacetic transaminase) >80 IU/L, SGPT (serum glutamic pyruvic transaminase) >80 IU/L, bilirubin >2.0 mg/dL or creatinine >2.0 mg/dL will be excluded regardless of the clinical condition
  • Patients who have a total blood eosinophil count ≥600/mm3
  • 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 a history of cancer, other than treated basal cell carcinoma, within the last 5 years
  • Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis
  • Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of a thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1
  • Patients with a history of asthma or allergic rhinitis
  • Patients with a history of and/or active alcohol or drug abuse
  • Patients with known active tuberculosis
  • Patients with an upper or lower respiratory tract infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period
  • Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction
  • Patients with known narrow-angle glaucoma
  • Patients with current significant psychiatric disorders
  • 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
  • Patients who are being treated with cromolyn sodium or nedocromil sodium
  • Patients who are being treated with antihistamines for any excluded allergic conditions
  • Patients using oral corticosteroid medication 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
  • Patients who initiated use of an inhaled steroid or changed doses less than 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period
  • Patients who are being treated with beta-blocker medications, MAO (monoamine oxidase) inhibitors or tricyclic antidepressants. Beta blocker eye medications (e.g., Betoptic) for treatment of non-narrow angle glaucoma are allowed
  • Patients who have had changes in their therapeutic plan within the last 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period
  • Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception
  • Patients with known hypersensitivity to anticholinergic drugs or any component of the ipratropium bromide/salbutamol Respimat® solution (including BAC (Benzalkonium chloride) and EDTA (Ethylenediaminetetraacetic acid)) or the ipratropium bromide/salbutamol MDI components
  • Previous participation in this study
  • Patients who are currently participating in another study

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Experimental

    Placebo Comparator

    Experimental

    Active Comparator

    Placebo Comparator

    Arm Label

    Ipratropium bromide / Salbutamol Inhalation solution

    Placebo Inhalation solution

    Ipratropium bromide Inhalation solution

    COMBIVENT Inhalation Aerosol (ipratropium bromide/salbutamol)

    Placebo Inhalation Aerosol

    Arm Description

    Outcomes

    Primary Outcome Measures

    FEV1 TAUC0-6 (Total area under the FEV1 (forced expiratory volume in one second) curve from 0 to 6 hours divided by six)

    Secondary Outcome Measures

    FEV1 TAUC0-6
    FEV1 TAUC0-8
    Peak FEV1 post treatment over two hours
    Change from baseline in Peak FEV1 response
    Area under the FEV1 curve from 0 to 6 hours above test-day baseline divided by six for normalization (AUC0-6)
    Onset of therapeutic FEV1 response
    Duration of therapeutic FEV1 response
    Time to peak FEV1 response
    TAUC0-6, TAUC0-8 and peak FVC (Forced vital capacity)
    Amount of beta agonist therapy used as rescue medication during the treatment period
    Number of patients using concomitant medication including corticosteroids during the treatment period
    Weekly means of daily symptom scores over the treatment period
    Number of patients with at least one COPD exacerbation
    Number of COPD exacerbations during the treatment period
    Physician's Global Evaluation
    Trough PEFR (peak expiratory flow rate) measured by the patient at home once daily
    Number of patients with adverse events
    Incidence of paradoxical bronchoconstriction on the test day
    Number of COPD exacerbation days
    Number of patients with clinically significant changes in vital signs
    Number of patients with abnormal changes in laboratory parameters
    Number of patients with abnormal changes in 12-lead electrocardiogram (ECG) parameters
    Plasma ipratropium and salbutamol concentrations
    Renal excretion amounts of ipratropium and salbutamol
    Length of COPD exacerbations during the treatment period

    Full Information

    First Posted
    June 20, 2014
    Last Updated
    June 26, 2014
    Sponsor
    Boehringer Ingelheim
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02177253
    Brief Title
    Ipratropium Bromide/Salbutamol Delivered by the Respimat® Inhaler Compared to Ipratropium Bromide Respimat®, COMBIVENT® Inhalation Aerosol and Placebo in Adults With Chronic Obstructive Pulmonary Disease
    Official Title
    A Comparison of Ipratropium Bromide/Salbutamol (40 mcg / 200 mcg, One Inhalation) Delivered by the Respimat ® Inhaler to COMBIVENT Inhalation Aerosol (Two Inhalations), Ipratropium Bromide Respimat ® and Placebo of Each Formulation in a 12-week, Double-blind, Safety and Efficacy Study in Adults With Chronic Obstructive Pulmonary Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2014
    Overall Recruitment Status
    Completed
    Study Start Date
    October 2002 (undefined)
    Primary Completion Date
    March 2004 (Actual)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Boehringer Ingelheim

    4. Oversight

    5. Study Description

    Brief Summary
    The primary objective of this study was to compare the long-term (12-week) bronchodilator efficacy and safety of ipratropium bromide / salbutamol combination administered by the Respimat® 40 mcg / 200 mcg (one inhalation q.i.d.) to COMBIVENT Inhalation Aerosol (two inhalations q.i.d.), ipratropium bromide Respimat® (one inhalation q.i.d.) and Placebo formulations of each in patients with Chronic Obstructive Pulmonary Disease (COPD). An additional objective was to show the superiority of Combivent Respimat as compared to ipratropium bromide (40 mcg) Respimat. Steady state pharmacokinetics over one dosing interval following four weeks of therapy were also characterized.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pulmonary Disease, Chronic Obstructive

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    Double
    Allocation
    Randomized
    Enrollment
    1118 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ipratropium bromide / Salbutamol Inhalation solution
    Arm Type
    Experimental
    Arm Title
    Placebo Inhalation solution
    Arm Type
    Placebo Comparator
    Arm Title
    Ipratropium bromide Inhalation solution
    Arm Type
    Experimental
    Arm Title
    COMBIVENT Inhalation Aerosol (ipratropium bromide/salbutamol)
    Arm Type
    Active Comparator
    Arm Title
    Placebo Inhalation Aerosol
    Arm Type
    Placebo Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Ipratropium bromide / Salbutamol
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo Inhalation solution
    Intervention Type
    Drug
    Intervention Name(s)
    Ipratropium bromide
    Intervention Type
    Drug
    Intervention Name(s)
    COMBIVENT Inhalation Aerosol
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo Inhalation Aerosol
    Primary Outcome Measure Information:
    Title
    FEV1 TAUC0-6 (Total area under the FEV1 (forced expiratory volume in one second) curve from 0 to 6 hours divided by six)
    Time Frame
    Day 85
    Secondary Outcome Measure Information:
    Title
    FEV1 TAUC0-6
    Time Frame
    Days 1, 29 and 57
    Title
    FEV1 TAUC0-8
    Time Frame
    Days 1, 29, 57 and 85
    Title
    Peak FEV1 post treatment over two hours
    Time Frame
    Days 1, 29, 57 and 85
    Title
    Change from baseline in Peak FEV1 response
    Time Frame
    Days 1, 29, 57 and 85
    Title
    Area under the FEV1 curve from 0 to 6 hours above test-day baseline divided by six for normalization (AUC0-6)
    Time Frame
    Days 1, 29, 57 and 85
    Title
    Onset of therapeutic FEV1 response
    Time Frame
    Days 1, 29, 57 and 85
    Title
    Duration of therapeutic FEV1 response
    Time Frame
    Days 1, 29, 57 and 85
    Title
    Time to peak FEV1 response
    Time Frame
    Days 1, 29, 57 and 85
    Title
    TAUC0-6, TAUC0-8 and peak FVC (Forced vital capacity)
    Time Frame
    Days 1, 29, 57 and 85
    Title
    Amount of beta agonist therapy used as rescue medication during the treatment period
    Time Frame
    up to day 85
    Title
    Number of patients using concomitant medication including corticosteroids during the treatment period
    Time Frame
    up to day 85
    Title
    Weekly means of daily symptom scores over the treatment period
    Time Frame
    up to day 85
    Title
    Number of patients with at least one COPD exacerbation
    Time Frame
    up to day 85
    Title
    Number of COPD exacerbations during the treatment period
    Time Frame
    up to day 85
    Title
    Physician's Global Evaluation
    Time Frame
    Days 1, 29, 57 and 85
    Title
    Trough PEFR (peak expiratory flow rate) measured by the patient at home once daily
    Time Frame
    up to day 85
    Title
    Number of patients with adverse events
    Time Frame
    up to day 85
    Title
    Incidence of paradoxical bronchoconstriction on the test day
    Time Frame
    up to day 85
    Title
    Number of COPD exacerbation days
    Time Frame
    up to day 85
    Title
    Number of patients with clinically significant changes in vital signs
    Time Frame
    Baseline, days 1, 29, 57 and 85
    Title
    Number of patients with abnormal changes in laboratory parameters
    Time Frame
    Days 29 and 85
    Title
    Number of patients with abnormal changes in 12-lead electrocardiogram (ECG) parameters
    Time Frame
    pre-treatment and 1 hour post-treatment on days 1, 29 and 85
    Title
    Plasma ipratropium and salbutamol concentrations
    Time Frame
    pre-treatment, 5, 15, 30 and 60 minutes and 2, 4 and 8 hours after inhalation of test drug on day 29
    Title
    Renal excretion amounts of ipratropium and salbutamol
    Time Frame
    0-2 hours, 2-8 hours at day 29
    Title
    Length of COPD exacerbations during the treatment period
    Time Frame
    up to day 85

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: All patients must have a diagnosis of COPD and the following spirometric criteria: Visit 1 (Screening) and Visit 2: Patients must have relatively stable, moderate to severe airway obstruction with an FEV1 ≤65% of predicted normal and FEV1 ≤70% of FVC Male or female patients 40 years of age or older Patients must have a smoking history of more than ten pack-years. A pack-year is defined as the equivalent of smoking one pack of 20 cigarettes per day for a year Patients must be able to perform pulmonary function tests and maintain records during the study period as required in the protocol Patients must be able to be trained in the proper use of an MDI (metered dose inhaler) and the Respimat® inhaler All patients must sign an Informed Consent Form prior to participation in the trial 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 relevant abnormal baseline hematology, blood chemistry or urinalysis. If the abnormality defines a disease listed as an exclusion criterion, the patient is excluded All patients with a SGOT (serum glutamic oxaloacetic transaminase) >80 IU/L, SGPT (serum glutamic pyruvic transaminase) >80 IU/L, bilirubin >2.0 mg/dL or creatinine >2.0 mg/dL will be excluded regardless of the clinical condition Patients who have a total blood eosinophil count ≥600/mm3 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 a history of cancer, other than treated basal cell carcinoma, within the last 5 years Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of a thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1 Patients with a history of asthma or allergic rhinitis Patients with a history of and/or active alcohol or drug abuse Patients with known active tuberculosis Patients with an upper or lower respiratory tract infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction Patients with known narrow-angle glaucoma Patients with current significant psychiatric disorders 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 Patients who are being treated with cromolyn sodium or nedocromil sodium Patients who are being treated with antihistamines for any excluded allergic conditions Patients using oral corticosteroid medication 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 Patients who initiated use of an inhaled steroid or changed doses less than 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period Patients who are being treated with beta-blocker medications, MAO (monoamine oxidase) inhibitors or tricyclic antidepressants. Beta blocker eye medications (e.g., Betoptic) for treatment of non-narrow angle glaucoma are allowed Patients who have had changes in their therapeutic plan within the last 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception Patients with known hypersensitivity to anticholinergic drugs or any component of the ipratropium bromide/salbutamol Respimat® solution (including BAC (Benzalkonium chloride) and EDTA (Ethylenediaminetetraacetic acid)) or the ipratropium bromide/salbutamol MDI components Previous participation in this study Patients who are currently participating in another study

    12. IPD Sharing Statement

    Links:
    URL
    http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1012/1012.46_U08-3586-01.pdf
    Description
    Related Info
    URL
    http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1012/1012.46_literature.pdf
    Description
    Related Info

    Learn more about this trial

    Ipratropium Bromide/Salbutamol Delivered by the Respimat® Inhaler Compared to Ipratropium Bromide Respimat®, COMBIVENT® Inhalation Aerosol and Placebo in Adults With Chronic Obstructive Pulmonary Disease

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