Clinical trial NCT01019694: Combivent Respimat 1-year Safety Study in Patients With Chronic Obstructive Pulmonary Disease
Official title: Patient Acceptability of Ipratropium Bromide/Albuteroll Delivered by the Respimat® Inhaler in Adults With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-11-25
Enrollment: 470
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 48
timeFrame: 48 weeks
Secondary outcomes:
measure: Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 3
timeFrame: 3 weeks
measure: Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 12
timeFrame: 12 weeks
measure: Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 24
timeFrame: 24 weeks
measure: Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 36
timeFrame: 36 weeks
measure: Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 0
timeFrame: 0 weeks
measure: Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 3
timeFrame: 3 weeks
measure: Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 12
timeFrame: 12 weeks
measure: Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 24
timeFrame: 24 weeks
measure: Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 36
timeFrame: 36 weeks
measure: Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 48
timeFrame: 48 weeks
measure: Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 0
timeFrame: 0 weeks
measure: Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 3
timeFrame: 3 weeks
measure: Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 12
timeFrame: 12 weeks
measure: Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 24
timeFrame: 24 weeks
measure: Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 36
timeFrame: 36 weeks
measure: Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 48
timeFrame: 48 weeks
measure: Physician's Global Evaluation at Week 0
timeFrame: 0 weeks
measure: Physician's Global Evaluation at Week 3
timeFrame: 3 weeks
measure: Physician's Global Evaluation at Week 12
timeFrame: 12 weeks
measure: Physician's Global Evaluation at Week 24
timeFrame: 24 weeks
measure: Physician's Global Evaluation at Week 36
timeFrame: 36 weeks
measure: Physician's Global Evaluation at Week 48
timeFrame: 48 weeks
measure: Change From Baseline in FEV1 at Day 1
timeFrame: baseline, day 1
measure: Change From Baseline in FEV1 at Week 12
timeFrame: baseline, 12 weeks
measure: Change From Baseline in FEV1 at Week 24
timeFrame: baseline, 24 weeks
measure: Change From Baseline in FEV1 at Week 48
timeFrame: baseline, 48 weeks
measure: Change From Baseline in FVC at Day 1
timeFrame: baseline, day 1
measure: Change From Baseline in FVC at Week 12
timeFrame: baseline, 12 weeks
measure: Change From Baseline in FVC at Week 24
timeFrame: baseline, 24 weeks
measure: Change From Baseline in FVC at Week 48
timeFrame: baseline, 48 weeks
measure: Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 0
timeFrame: 0 weeks
measure: Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 3
timeFrame: 3 weeks
measure: Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 12
timeFrame: 12 weeks
measure: Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 24
timeFrame: 24 weeks
measure: Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 36
timeFrame: 36 weeks
measure: Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 48
timeFrame: 48 weeks
measure: Number of Patients Having Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
timeFrame: 48 weeks
measure: Number of Patients Having Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Leading to Hospitalization
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Jasper
country: United States
facility: 1012.62.153 Boehringer Ingelheim Investigational Site
state: Alabama
city: Mobile
country: United States
facility: 1012.62.145 Boehringer Ingelheim Investigational Site
state: Alabama
city: Mesa
country: United States
facility: 1012.62.156 Boehringer Ingelheim Investigational Site
state: Arizona
city: Berkeley
country: United States
facility: 1012.62.135 Boehringer Ingelheim Investigational Site
state: California
city: Riverside
country: United States
facility: 1012.62.141 Boehringer Ingelheim Investigational Site
state: California
city: Boulder
country: United States
facility: 1012.62.155 Boehringer Ingelheim Investigational Site
state: Colorado
city: Fort Collins
country: United States
facility: 1012.62.126 Boehringer Ingelheim Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: 1012.62.131 Boehringer Ingelheim Investigational Site
state: Colorado
city: Stamford
country: United States
facility: 1012.62.144 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Waterbury
country: United States
facility: 1012.62.123 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Clearwater
country: United States
facility: 1012.62.114 Boehringer Ingelheim Investigational Site
state: Florida
city: Deland
country: United States
facility: 1012.62.124 Boehringer Ingelheim Investigational Site
state: Florida
city: Pensacola
country: United States
facility: 1012.62.139 Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: 1012.62.134 Boehringer Ingelheim Investigational Site
state: Florida
city: Winter Park
country: United States
facility: 1012.62.115 Boehringer Ingelheim Investigational Site
state: Florida
city: Decatur
country: United States
facility: 1012.62.146 Boehringer Ingelheim Investigational Site
state: Georgia
city: Coeur d'Alene
country: United States
facility: 1012.62.113 Boehringer Ingelheim Investigational Site
state: Idaho
city: Dubuque
country: United States
facility: 1012.62.157 Boehringer Ingelheim Investigational Site
state: Iowa
city: Louisville
country: United States
facility: 1012.62.159 Boehringer Ingelheim Investigational Site
state: Kentucky
city: Lafayette
country: United States
facility: 1012.62.116 Boehringer Ingelheim Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: 1012.62.148 Boehringer Ingelheim Investigational Site
state: Louisiana
city: North Dartmouth
country: United States
facility: 1012.62.137 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: 1012.62.132 Boehringer Ingelheim Investigational Site
state: Michigan
city: Livonia
country: United States
facility: 1012.62.117 Boehringer Ingelheim Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: 1012.62.158 Boehringer Ingelheim Investigational Site
state: Minnesota
city: St. Louis
country: United States
facility: 1012.62.127 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: 1012.62.129 Boehringer Ingelheim Investigational Site
state: Missouri
city: Cherry Hill
country: United States
facility: 1012.62.147 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Summit
country: United States
facility: 1012.62.149 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: 1012.62.112 Boehringer Ingelheim Investigational Site
state: New Mexico
city: Rochester
country: United States
facility: 1012.62.111 Boehringer Ingelheim Investigational Site
state: New York
city: Cincinnati
country: United States
facility: 1012.62.107 Boehringer Ingelheim Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: 1012.62.120 Boehringer Ingelheim Investigational Site
state: Ohio
city: Toledo
country: United States
facility: 1012.62.150 Boehringer Ingelheim Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: 1012.62.103 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: 1012.62.104 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: East Providence
country: United States
facility: 1012.62.154 Boehringer Ingelheim Investigational Site
state: Rhode Island
city: Charleston
country: United States
facility: 1012.62.128 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Easley
country: United States
facility: 1012.62.130 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: 1012.62.151 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: 1012.62.161 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greer
country: United States
facility: 1012.62.109 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1012.62.118 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Austin
country: United States
facility: 1012.62.125 Boehringer Ingelheim Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: 1012.62.140 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1012.62.143 Boehringer Ingelheim Investigational Site
state: Texas
city: Killeen
country: United States
facility: 1012.62.152 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1012.62.102 Boehringer Ingelheim Investigational Site
state: Texas
city: Danville
country: United States
facility: 1012.62.122 Boehringer Ingelheim Investigational Site
state: Virginia
city: Richmond
country: United States
facility: 1012.62.119 Boehringer Ingelheim Investigational Site
state: Virginia
city: Richmond
country: United States
facility: 1012.62.142 Boehringer Ingelheim Investigational Site
state: Virginia
city: Spokane
country: United States
facility: 1012.62.108 Boehringer Ingelheim Investigational Site
state: Washington
city: Spokane
country: United States
facility: 1012.62.133 Boehringer Ingelheim Investigational Site
state: Washington
city: Tacoma
country: United States
facility: 1012.62.105 Boehringer Ingelheim Investigational Site
state: Washington
city: Morgantown
country: United States
facility: 1012.62.101 Boehringer Ingelheim Investigational Site
state: West Virginia
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.