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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01019694
• Other study ID #: 1012.62
• Status: Completed
• Phase: Phase 3
• First received: November 16, 2009
• Last updated: October 14, 2014
• Start date: November 2009

Study information

• Verified date: October 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 470
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Combivent CFC-MDI
36/206 mcg Four times a day (QID)
• Combivent Respimat 20/100 mcg
Open label randomized parallel
• Atrovent HFA 42 mcg + Albuterol HFA 200 mcg
Open label randomized parallel

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Number of Patients Having Chronic Obstructive Pulmonary Disease (COPD) Exacerbations		48 weeks	No
Secondary	Number of Patients Having Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Leading to Hospitalization		48 weeks	No

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