Combivent Respimat 1-year Safety Study in Patients With Chronic Obstructive Pulmonary Disease

Patient Acceptability of Ipratropium Bromide/Albuteroll Delivered by the Respimat® Inhaler in Adults With Chronic Obstructive Pulmonary Disease

The primary objective of this study is to evaluate long-term safety and patient acceptability of COMBIVENT RESPIMAT Inhalation Spray as compared to the COMBIVENT Inhalation Aerosol Chlorofluorocarbon-Metered Dose Inhaler (CFC-MDI) and the free combination of ATROVENT Hydrofluoroalkane (HFA) and albuterol Hydrofluoroalkane (HFA) inhalation aerosols.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Combivent Respimat 20/100 mcg; Drug: Combivent CFC-MDI; Drug: Atrovent HFA 42 mcg + Albuterol HFA 200 mcg

• Study Type: Interventional
• Enrollment (Actual): 470
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Jasper, Alabama, United States
      • 1012.62.153 Boehringer Ingelheim Investigational Site
    • Mobile, Alabama, United States
      • 1012.62.145 Boehringer Ingelheim Investigational Site
  • Arizona
    • Mesa, Arizona, United States
      • 1012.62.156 Boehringer Ingelheim Investigational Site
  • California
    • Berkeley, California, United States
      • 1012.62.135 Boehringer Ingelheim Investigational Site
    • Riverside, California, United States
      • 1012.62.141 Boehringer Ingelheim Investigational Site
  • Colorado
    • Boulder, Colorado, United States
      • 1012.62.155 Boehringer Ingelheim Investigational Site
    • Fort Collins, Colorado, United States
      • 1012.62.126 Boehringer Ingelheim Investigational Site
    • Wheat Ridge, Colorado, United States
      • 1012.62.131 Boehringer Ingelheim Investigational Site
  • Connecticut
    • Stamford, Connecticut, United States
      • 1012.62.144 Boehringer Ingelheim Investigational Site
    • Waterbury, Connecticut, United States
      • 1012.62.123 Boehringer Ingelheim Investigational Site
  • Florida
    • Clearwater, Florida, United States
      • 1012.62.114 Boehringer Ingelheim Investigational Site
    • Deland, Florida, United States
      • 1012.62.124 Boehringer Ingelheim Investigational Site
    • Pensacola, Florida, United States
      • 1012.62.139 Boehringer Ingelheim Investigational Site
    • Tampa, Florida, United States
      • 1012.62.134 Boehringer Ingelheim Investigational Site
    • Winter Park, Florida, United States
      • 1012.62.115 Boehringer Ingelheim Investigational Site
  • Georgia
    • Decatur, Georgia, United States
      • 1012.62.146 Boehringer Ingelheim Investigational Site
  • Idaho
    • Coeur d'Alene, Idaho, United States
      • 1012.62.113 Boehringer Ingelheim Investigational Site
  • Iowa
    • Dubuque, Iowa, United States
      • 1012.62.157 Boehringer Ingelheim Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States
      • 1012.62.159 Boehringer Ingelheim Investigational Site
  • Louisiana
    • Lafayette, Louisiana, United States
      • 1012.62.116 Boehringer Ingelheim Investigational Site
    • New Orleans, Louisiana, United States
      • 1012.62.148 Boehringer Ingelheim Investigational Site
  • Massachusetts
    • North Dartmouth, Massachusetts, United States
      • 1012.62.137 Boehringer Ingelheim Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States
      • 1012.62.132 Boehringer Ingelheim Investigational Site
    • Livonia, Michigan, United States
      • 1012.62.117 Boehringer Ingelheim Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States
      • 1012.62.158 Boehringer Ingelheim Investigational Site
  • Missouri
    • St. Louis, Missouri, United States
      • 1012.62.127 Boehringer Ingelheim Investigational Site
    • St. Louis, Missouri, United States
      • 1012.62.129 Boehringer Ingelheim Investigational Site
  • New Jersey
    • Cherry Hill, New Jersey, United States
      • 1012.62.147 Boehringer Ingelheim Investigational Site
    • Summit, New Jersey, United States
      • 1012.62.149 Boehringer Ingelheim Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States
      • 1012.62.112 Boehringer Ingelheim Investigational Site
  • New York
    • Rochester, New York, United States
      • 1012.62.111 Boehringer Ingelheim Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States
      • 1012.62.107 Boehringer Ingelheim Investigational Site
    • Cincinnati, Ohio, United States
      • 1012.62.120 Boehringer Ingelheim Investigational Site
    • Toledo, Ohio, United States
      • 1012.62.150 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • 1012.62.103 Boehringer Ingelheim Investigational Site
    • Pittsburgh, Pennsylvania, United States
      • 1012.62.104 Boehringer Ingelheim Investigational Site
  • Rhode Island
    • East Providence, Rhode Island, United States
      • 1012.62.154 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States
      • 1012.62.128 Boehringer Ingelheim Investigational Site
    • Easley, South Carolina, United States
      • 1012.62.130 Boehringer Ingelheim Investigational Site
    • Greenville, South Carolina, United States
      • 1012.62.151 Boehringer Ingelheim Investigational Site
    • Greenville, South Carolina, United States
      • 1012.62.161 Boehringer Ingelheim Investigational Site
    • Greer, South Carolina, United States
      • 1012.62.109 Boehringer Ingelheim Investigational Site
    • Spartanburg, South Carolina, United States
      • 1012.62.118 Boehringer Ingelheim Investigational Site
  • Texas
    • Austin, Texas, United States
      • 1012.62.125 Boehringer Ingelheim Investigational Site
    • Fort Worth, Texas, United States
      • 1012.62.140 Boehringer Ingelheim Investigational Site
    • Houston, Texas, United States
      • 1012.62.143 Boehringer Ingelheim Investigational Site
    • Killeen, Texas, United States
      • 1012.62.152 Boehringer Ingelheim Investigational Site
    • San Antonio, Texas, United States
      • 1012.62.102 Boehringer Ingelheim Investigational Site
  • Virginia
    • Danville, Virginia, United States
      • 1012.62.122 Boehringer Ingelheim Investigational Site
    • Richmond, Virginia, United States
      • 1012.62.119 Boehringer Ingelheim Investigational Site
    • Richmond, Virginia, United States
      • 1012.62.142 Boehringer Ingelheim Investigational Site
  • Washington
    • Spokane, Washington, United States
      • 1012.62.108 Boehringer Ingelheim Investigational Site
    • Spokane, Washington, United States
      • 1012.62.133 Boehringer Ingelheim Investigational Site
    • Tacoma, Washington, United States
      • 1012.62.105 Boehringer Ingelheim Investigational Site
  • West Virginia
    • Morgantown, West Virginia, United States
      • 1012.62.101 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. All patients must sign an informed consent consistent with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines prior to participation in the trial.
2. Male or female patients 40 years of age or older.
3. Patients must be current or ex-smokers with a smoking history of 10 pack-years. (Patients who have never smoked cigarettes must be excluded) Pack Years = Number of cigarettes/day x years of smoking 20 cigarettes/pack
4. All patients must have a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (P95-4381), and must meet the following spirometric criteria at Visit 1:Relatively stable, moderate to severe airway obstruction with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) < 80% of predicted normal and FEV1/Forced Vital Capacity (FVC) < 70%. Spirometry should be done at baseline and approximately 1/2 hour following 4 inhalations of albuterol. Predicted normal values will be calculated according to European Coal and Steel Community (ECSC), European Community for Coal and Steel (ECCS), (R94-1408). For Height measured in inches Males: FEV1 predicted (L) = 4.30 x [height (inches) / 39.37]-0.029 x age (yrs) - 2.49 Females: FEV1 predicted (L) = 3.95 x [height (inches) / 39.37]-0.025 x age (yrs) - 2.60 For Height measured in meters Males: FEV1 predicted (L) = 4.30 x [height (meters)] - 0.029 x age (years) -2.49 Females: FEV1 predicted (L) = 3.95 x [height (meters)] - 0.025 x age (years) - 2.60
5. Patients must be able to perform all study related procedures and maintain study records during the study period as required in the protocol.
6. Patients must be able to inhale medication in a competent manner from the RESPIMAT inhaler and from a metered dose inhaler (MDI).

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 a recent history (i.e., one year or less) of myocardial infarction.
3. Patients who have been hospitalized or being treated for heart failure within the past year.
4. Patients with clinically unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy within the past year.
5. Patients with a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with fully cured squamous cell or treated basal cell carcinoma are allowed).
6. Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis.
7. 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.
8. Patients with a current diagnosis of asthma.
9. Patients with a history of significant alcohol or drug abuse.
10. Patients with known active tuberculosis.
11. Patients using beta blocker medications are excluded. Cardioselective beta blockers are allowed with caution. Beta blocker eye medications for treatment of non-narrow angle glaucoma are allowed.
12. Patients who regularly use daytime oxygen therapy for more than 1 hour per day Continuous Positive Airway Pressure (CPAP for sleep apnea is allowed).
13. Patients using oral corticosteroid medication at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day, except as required for treatment of exacerbation during the study.
14. Pregnant or nursing women.
15. Women of childbearing potential not using a medically approved means of contraception (i.e., oral or injectable contraceptives, intrauterine devices or diaphragm with spermicide, or transdermal hormonal patches). Abstinence will not be accepted as a medically approved means of contraception. Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.
16. Patients with known hypersensitivity to anticholinergic drugs, any other component of the ipratropium bromide/albuterol RESPIMAT solution including Benzalkonium chloride (BAC) and Ethylenediaminetetraacetic acid (EDTA) or the ipratropium bromide/albuterol Chlorofluorocarbons (CFC) MDI or Hydrofluoroalkane (HFA) components.
17. Previous participation in this study. (The patient cannot re-enroll into this study.)
18. Patients who are currently participating in another interventional study.
19. Patients who have taken an investigational drug within 1 month or 6 half lives (whichever is greater) prior to screening.
20. Patients currently in any pulmonary rehabilitation program or scheduled to participate in any such program during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Combivent Respimat 20/100 microgram(mcg); patient to take 1 inhalation 4 times a day	Drug: Combivent Respimat 20/100 mcg; Open label randomized parallel
ACTIVE_COMPARATOR: Combivent CFC-MDI 36/206 microgram-mcg; patient to take 2 inhalations 4 times a day	Drug: Combivent CFC-MDI; 36/206 mcg Four times a day (QID)
ACTIVE_COMPARATOR: Atrovent HFA 42 mcg + Albuterol HFA; patient to take 2 inhalations of each 4 times a day	Drug: Atrovent HFA 42 mcg + Albuterol HFA 200 mcg; Open label randomized parallel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 48	Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied).	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 3	Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied).	3 weeks
Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 12	Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied).	12 weeks
Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 24	Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied).	24 weeks
Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 36	Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied).	36 weeks
Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 0	Patient satisfaction was assessed by asking: "Overall, how satisfied are you with your inhaler?". Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied).	0 weeks
Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 3	Patient satisfaction was assessed by asking: "Overall, how satisfied are you with your inhaler?". Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied).	3 weeks
Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 12	Patient satisfaction was assessed by asking: "Overall, how satisfied are you with your inhaler?". Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied).	12 weeks
Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 24	Patient satisfaction was assessed by asking: "Overall, how satisfied are you with your inhaler?". Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied).	24 weeks
Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 36	Patient satisfaction was assessed by asking: "Overall, how satisfied are you with your inhaler?". Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied).	36 weeks
Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 48	Patient satisfaction was assessed by asking: "Overall, how satisfied are you with your inhaler?". Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied).	48 weeks
Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 0	CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited).	0 weeks
Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 3	CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited).	3 weeks
Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 12	CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited).	12 weeks
Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 24	CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited).	24 weeks
Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 36	CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited).	36 weeks
Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 48	CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited).	48 weeks
Physician's Global Evaluation at Week 0	Physicians evaluated the patient's overall clinical condition on a scale ranging from "poor" (score 1 or 2) to "excellent" (score 7 or 8).	0 weeks
Physician's Global Evaluation at Week 3	Physicians evaluated the patient's overall clinical condition on a scale ranging from "poor" (score 1 or 2) to "excellent" (score 7 or 8).	3 weeks
Physician's Global Evaluation at Week 12	Physicians evaluated the patient's overall clinical condition on a scale ranging from "poor" (score 1 or 2) to "excellent" (score 7 or 8).	12 weeks
Physician's Global Evaluation at Week 24	Physicians evaluated the patient's overall clinical condition on a scale ranging from "poor" (score 1 or 2) to "excellent" (score 7 or 8).	24 weeks
Physician's Global Evaluation at Week 36	Physicians evaluated the patient's overall clinical condition on a scale ranging from "poor" (score 1 or 2) to "excellent" (score 7 or 8).	36 weeks
Physician's Global Evaluation at Week 48	Physicians evaluated the patient's overall clinical condition on a scale ranging from "poor" (score 1 or 2) to "excellent" (score 7 or 8).	48 weeks
Change From Baseline in FEV1 at Day 1	Change from test-day baseline in Forced Expiratory Volume in 1 second (FEV1) at 1 hour post dose on test day 1.	baseline, day 1
Change From Baseline in FEV1 at Week 12	Change from test-day baseline in Forced Expiratory Volume in 1 second (FEV1) at 1 hour post dose at Week 12	baseline, 12 weeks
Change From Baseline in FEV1 at Week 24	Change from test-day baseline in Forced Expiratory Volume in 1 second (FEV1) at 1 hour post dose at Week 24	baseline, 24 weeks
Change From Baseline in FEV1 at Week 48	Change from test-day baseline in Forced Expiratory Volume in 1 second (FEV1) at 1 hour post dose at Week 48	baseline, 48 weeks
Change From Baseline in FVC at Day 1	Change from test-day baseline in Forced Vital Capacity (FVC) at 1 hour post dose on test day 1.	baseline, day 1
Change From Baseline in FVC at Week 12	Change from test-day baseline in Forced Vital Capacity (FVC) at 1 hour post dose at Week 12	baseline, 12 weeks
Change From Baseline in FVC at Week 24	Change from test-day baseline in Forced Vital Capacity (FVC) at 1 hour post dose at Week 24	baseline, 24 weeks
Change From Baseline in FVC at Week 48	Change from test-day baseline in Forced Vital Capacity (FVC) at 1 hour post dose at Week 48	baseline, 48 weeks
Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 0	Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 0	0 weeks
Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 3	Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 3	3 weeks
Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 12	Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 12	12 weeks
Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 24	Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 24	24 weeks
Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 36	Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 36	36 weeks
Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 48	Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 48	48 weeks
Number of Patients Having Chronic Obstructive Pulmonary Disease (COPD) Exacerbations		48 weeks
Number of Patients Having Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Leading to Hospitalization		48 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Ferguson GT, Ghafouri M, Dai L, Dunn LJ. COPD patient satisfaction with ipratropium bromide/albuterol delivered via Respimat: a randomized, controlled study. Int J Chron Obstruct Pulmon Dis. 2013;8:139-50. doi: 10.2147/COPD.S38577. Epub 2013 Mar 19.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: November 16, 2009
• First Submitted That Met QC Criteria: November 24, 2009
• First Posted (ESTIMATE): November 25, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): October 23, 2014
• Last Update Submitted That Met QC Criteria: October 14, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Ipratropium
• Other Study ID Numbers: 1012.62