Clinical trial NCT00782509: 12 / 48 wk Pivotal PFT vs PBO in COPD II
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: 644
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).


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 of Daily Daytime Rescue Use
timeFrame: Week 48
measure: Weekly Mean of Daily Nighttime Rescue Use
timeFrame: Week 48
measure: Weekly Mean of Daily (24h) Rescue Use
timeFrame: 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: Mobile
country: United States
facility: 1222.12.1227 Boehringer Ingelheim Investigational Site
state: Alabama
city: Wheat Ridge
country: United States
facility: 1222.12.1218 Boehringer Ingelheim Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: 1222.12.1226 Boehringer Ingelheim Investigational Site
state: Colorado
city: Waterbury
country: United States
facility: 1222.12.1214 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Clearwater
country: United States
facility: 1222.12.1207 Boehringer Ingelheim Investigational Site
state: Florida
city: Panama City
country: United States
facility: 1222.12.1224 Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: 1222.12.1222 Boehringer Ingelheim Investigational Site
state: Florida
city: Winter Park
country: United States
facility: 1222.12.1208 Boehringer Ingelheim Investigational Site
state: Florida
city: River Forest
country: United States
facility: 1222.12.1220 Boehringer Ingelheim Investigational Site
state: Illinois
city: New Orleans
country: United States
facility: 1222.12.1229 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Ann Arbor
country: United States
facility: 1222.12.1219 Boehringer Ingelheim Investigational Site
state: Michigan
city: Livonia
country: United States
facility: 1222.12.1209 Boehringer Ingelheim Investigational Site
state: Michigan
city: Henderson
country: United States
facility: 1222.12.1233 Boehringer Ingelheim Investigational Site
state: Nevada
city: Summit
country: United States
facility: 1222.12.1228 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: 1222.12.1206 Boehringer Ingelheim Investigational Site
state: New Mexico
city: Rochester
country: United States
facility: 1222.12.1205 Boehringer Ingelheim Investigational Site
state: New York
city: Elizabeth City
country: United States
facility: 1222.12.1213 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Harrisburg
country: United States
facility: 1222.12.1223 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: 1222.12.1217 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Cincinnatti
country: United States
facility: 1222.12.1203 Boehringer Ingelheim Investigational Site
state: Ohio
city: Pittsburgh
country: United States
facility: 1222.12.1201 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Easley
country: United States
facility: 1222.12.1230 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: 1222.12.1216 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: 1222.12.1221 Boehringer Ingelheim Investigational Site
state: Texas
city: Danville
country: United States
facility: 1222.12.1212 Boehringer Ingelheim Investigational Site
state: Virginia
city: Richmond
country: United States
facility: 1222.12.1211 Boehringer Ingelheim Investigational Site
state: Virginia
city: Richmond
country: United States
facility: 1222.12.1225 Boehringer Ingelheim Investigational Site
state: Virginia
city: Morgantown
country: United States
facility: 1222.12.1232 Boehringer Ingelheim Investigational Site
state: West Virginia
city: Beijing
country: China
facility: 1222.12.1298 Boehringer Ingelheim Investigational Site
city: Chongqing
country: China
facility: 1222.12.1301 Boehringer Ingelheim Investigational Site
city: Guangzhou
country: China
facility: 1222.12.1305 Boehringer Ingelheim Investigational Site
city: Haikou
country: China
facility: 1222.12.1306 Boehringer Ingelheim Investigational Site
city: Hangzhou
country: China
facility: 1222.12.1302 Boehringer Ingelheim Investigational Site
city: Nanjing
country: China
facility: 1222.12.1304 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1222.12.1296 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1222.12.1297 Boehringer Ingelheim Investigational Site
city: Wuhan
country: China
facility: 1222.12.1303 Boehringer Ingelheim Investigational Site
city: Xi'An
country: China
facility: 1222.12.1299 Boehringer Ingelheim Investigational Site
city: Xi'An
country: China
facility: 1222.12.1300 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.12.1269 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.12.1270 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.12.1271 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1222.12.1268 Boehringer Ingelheim Investigational Site
city: Koblenz
country: Germany
facility: 1222.12.1266 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 1222.12.1272 Boehringer Ingelheim Investigational Site
city: Rüdersdorf
country: Germany
facility: 1222.12.1267 Boehringer Ingelheim Investigational Site
city: Kaohsiung County
country: Taiwan
facility: 1222.12.1289 Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: 1222.12.1290 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 1222.12.1288 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1222.12.1287 Boehringer Ingelheim Investigational Site
city: Taoyuan
country: Taiwan
facility: 1222.12.1286 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.