Clinical trial NCT00782210: 12 / 48 Week Pivotal PFT vs PBO in COPD I
Official title: Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 mcg [2 Actuations of 2.5 mcg] and 10 mcg [2 Actuations of 5 mcg]) Delivered by the Respimat® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-10-31
Enrollment: 625
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: This primary objective of this study is to compare two doses of BI 1744 CL inhalation solution delivered by the Respimat® inhaler once daily to placebo in patients with chronic obstructive pulmonary disease (COPD).

The safety of BI 1744 CL inhalation solution delivered through the Respimat inhaler will also be compared to placebo.


Eligibility criteria: Inclusion criteria:

* All patients must have a diagnosis of chronic obstructive pulmonary disease
* Male or female patients, 40 years of age or older Patients must be current or ex-smokers with a smoking history of more than 10 pack years Post bronchodilator FEV1 \<80% predicted and post-bronchodilator FEV1/FVC \<70%

Exclusion criteria:

* Patients with a significant disease other than COPD
* Patients with a history of asthma
* Patients with any of the following conditions:

a history of myocardial infarction within 1 year of screening visit (Visit 1) unstable or life-threatening cardiac arrhythmia. have been hospitalized for heart failure within the past year. known active tuberculosis a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed) a history of life-threatening pulmonary obstruction a history of cystic fibrosis

Primary outcomes:
measure: Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Day 85
measure: Trough FEV1 Response at Day 85 (12 Weeks)
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h and - 10 mins prior to study drug at Day 85.
Secondary outcomes:
measure: Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)
measure: Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at day 1
measure: Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
measure: Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -1h, -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
measure: Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
measure: Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
measure: Trough FEV1 Response After 2 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 2 weeks
measure: Trough FEV1 Response After 6 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 6 weeks
measure: Trough FEV1 Response After 18 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 18 weeks
measure: Trough FEV1 Response After 24 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 24 weeks
measure: Trough FEV1 Response After 32 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 32 weeks
measure: Trough FEV1 Response After 40 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 40 weeks
measure: Trough FEV1 Response After 48 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 48 weeks
measure: Peak FEV1 (0-3h) Response At Day 1
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1
measure: Peak FEV1 (0-3h) Response After 2 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
measure: Peak FEV1 (0-3h) Response After 6 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
measure: Peak FEV1 (0-3h) Response After 12 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
measure: Peak FEV1 (0-3h) Response After 24 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
measure: Peak FEV1 (0-3h) Response After 48 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
measure: Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1
measure: Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
measure: FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
measure: FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
measure: FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
measure: FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
measure: Trough FVC Response After 2 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 2 weeks
measure: Trough FVC Response After 6 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 6 weeks
measure: Trough FVC Response After 12 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 12 weeks
measure: Trough FVC Response After 18 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 18 weeks
measure: Trough FVC Response After 24 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 24 weeks
measure: Trough FVC Response After 32 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 32 weeks
measure: Trough FVC Response After 40 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 40 weeks
measure: Trough FVC Response After 48 Weeks
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 48 weeks
measure: FVC Peak (0-3h) Response At Day 1
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1
measure: FVC Peak (0-3h) Response After 2 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
measure: FVC Peak (0-3h) Response After 6 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
measure: FVC Peak (0-3h) Response After 12 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
measure: FVC Peak (0-3h) Response After 24 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
measure: FVC Peak (0-3h) Response After 48 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
measure: Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)
measure: Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)
timeFrame: immediately upon arising (before drug administration) from Screening to week 48
measure: Weekly Mean Evening Peak Expiratory Flow Rate (PEF)
timeFrame: at bedtime from Screening to week 48
measure: Weekly Mean Daytime Rescue Use
timeFrame: From Screening to week 48
measure: Weekly Mean Nighttime Rescue Use
timeFrame: From Screening to week 48
measure: Weekly Mean Daily (24h) Rescue Use
timeFrame: From Screening to week 48
measure: Patient's Global Rating at Week 6
timeFrame: Week 6 visit
measure: Patient's Global Rating at Week 12
timeFrame: Week 12 visit
measure: Patient's Global Rating at Week 24
timeFrame: Week 24 visit
measure: Patient's Global Rating at Week 48
timeFrame: Week 48 visit
measure: Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
timeFrame: Baseline to end of study at 48 weeks.
measure: Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization
timeFrame: Baseline to end of study at 48 weeks.
measure: Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
timeFrame: Baseline to end of study at 48 weeks.
measure: Number of COPD Exacerbations
timeFrame: Baseline to end of study at week 48 visit
measure: Number of COPD Exacerbations Requiring Hospitalization
timeFrame: Baseline to end of study at week 48 visit
measure: Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
timeFrame: Baseline to end of study at 48 weeks.
measure: Changes in Safety Parameters Related to Treatment
timeFrame: 48 weeks
measure: Change From Baseline in Potassium
timeFrame: Day 1 and at 12, 24 and 48 weeks
Other outcomes:
Locations:
city: Jasper
country: United States
facility: 1222.11.1122 Boehringer Ingelheim Investigational Site
state: Alabama
city: Berkeley
country: United States
facility: 1222.11.1116 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1222.11.1121 Boehringer Ingelheim Investigational Site
state: California
city: Fort Collins
country: United States
facility: 1222.11.1111 Boehringer Ingelheim Investigational Site
state: Colorado
city: Stamford
country: United States
facility: 1222.11.1117 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Deland
country: United States
facility: 1222.11.1110 Boehringer Ingelheim Investigational Site
state: Florida
city: Coeur d'Alene
country: United States
facility: 1222.11.1106 Boehringer Ingelheim Investigational Site
state: Idaho
city: Evansville
country: United States
facility: 1222.11.1108 Boehringer Ingelheim Investigational Site
state: Indiana
city: Bowling Green
country: United States
facility: 1222.11.1109 Boehringer Ingelheim Investigational Site
state: Kentucky
city: St. Louis
country: United States
facility: 1222.11.1113 Boehringer Ingelheim Investigational Site
state: Missouri
city: Larchmont
country: United States
facility: 1222.11.1115 Boehringer Ingelheim Investigational Site
state: New York
city: Toledo
country: United States
facility: 1222.11.1120 Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: 1222.11.1105 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Charleston
country: United States
facility: 1222.11.1112 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greer
country: United States
facility: 1222.11.1119 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Union
country: United States
facility: 1222.11.1102 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Killeen
country: United States
facility: 1222.11.1124 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1222.11.1101 Boehringer Ingelheim Investigational Site
state: Texas
city: Spokane
country: United States
facility: 1222.11.1103 Boehringer Ingelheim Investigational Site
state: Washington
city: Spokane
country: United States
facility: 1222.11.1114 Boehringer Ingelheim Investigational Site
state: Washington
city: Tacoma
country: United States
facility: 1222.11.1123 Boehringer Ingelheim Investigational Site
state: Washington
city: Concord
country: Australia
facility: 1222.11.1143 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Glebe
country: Australia
facility: 1222.11.1145 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Westmead
country: Australia
facility: 1222.11.1144 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Toorak Gardens
country: Australia
facility: 1222.11.1142 Boehringer Ingelheim Investigational Site
state: South Australia
city: Woodville
country: Australia
facility: 1222.11.1141 Boehringer Ingelheim Investigational Site
state: South Australia
city: Beijing
country: China
facility: 1222.11.1166 Boehringer Ingelheim Investigational Site
city: Changsha
country: China
facility: 1222.11.1171 Boehringer Ingelheim Investigational Site
city: Chengdu
country: China
facility: 1222.11.1170 Boehringer Ingelheim Investigational Site
city: Chongqing
country: China
facility: 1222.11.1169 Boehringer Ingelheim Investigational Site
city: Da lian
country: China
facility: 1222.11.1172 Boehringer Ingelheim Investigational Site
city: Guangzhou
country: China
facility: 1222.11.1163 Boehringer Ingelheim Investigational Site
city: Nanjing
country: China
facility: 1222.11.1167 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1222.11.1164 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1222.11.1165 Boehringer Ingelheim Investigational Site
city: Shenyang
country: China
facility: 1222.11.1173 Boehringer Ingelheim Investigational Site
city: Xi'An
country: China
facility: 1222.11.1168 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.11.1151 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.11.1156 Boehringer Ingelheim Investigational Site
city: Erfurt
country: Germany
facility: 1222.11.1157 Boehringer Ingelheim Investigational Site
city: Halle
country: Germany
facility: 1222.11.1154 Boehringer Ingelheim Investigational Site
city: Kassel
country: Germany
facility: 1222.11.1153 Boehringer Ingelheim Investigational Site
city: Oschersleben
country: Germany
facility: 1222.11.1158 Boehringer Ingelheim Investigational Site
city: Potsdam
country: Germany
facility: 1222.11.1152 Boehringer Ingelheim Investigational Site
city: Weinheim
country: Germany
facility: 1222.11.1155 Boehringer Ingelheim Investigational Site
city: Hamilton
country: New Zealand
facility: 1222.11.1138 Boehringer Ingelheim Investigational Site
city: Otahuhu
country: New Zealand
facility: 1222.11.1139 Boehringer Ingelheim Investigational Site
city: Tauranga
country: New Zealand
facility: 1222.11.1136 Boehringer Ingelheim Investigational Site
city: Wellington
country: New Zealand
facility: 1222.11.1137 Boehringer Ingelheim Investigational Site
city: Changhua
country: Taiwan
facility: 1222.11.1180 Boehringer Ingelheim Investigational Site
city: Chia-Yi
country: Taiwan
facility: 1222.11.1181 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 1222.11.1179 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1222.11.1177 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1222.11.1178 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Singh D, Wedzicha JA, Siddiqui S, de la Hoz A, Xue W, Magnussen H, Miravitlles M, Chalmers JD, Calverley PMA. Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials. Respir Res. 2020 Sep 17;21(1):240. doi: 10.1186/s12931-020-01482-1.
citation: Andreas S, Bothner U, de la Hoz A, Kloer I, Trampisch M, Alter P. A Post Hoc Holter ECG Analysis of Olodaterol and Formoterol in Moderate-to-Very-Severe COPD. Int J Chron Obstruct Pulmon Dis. 2020 Aug 10;15:1955-1965. doi: 10.2147/COPD.S246353. eCollection 2020.
citation: Andreas S, Bothner U, Trampisch M, Haensel M, Buhl R, Alter P. Effect of long-acting beta2-agonists olodaterol and formoterol on heart rate and blood pressure in chronic obstructive pulmonary disease patients. Pulm Pharmacol Ther. 2018 Oct;52:1-6. doi: 10.1016/j.pupt.2018.08.002. Epub 2018 Aug 2.
citation: Ferguson GT, Feldman GJ, Hofbauer P, Hamilton A, Allen L, Korducki L, Sachs P. Efficacy and safety of olodaterol once daily delivered via Respimat(R) in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014 Jun 16;9:629-45. doi: 10.2147/COPD.S61717. eCollection 2014.