Clinical trial NCT00452400: Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Patients With COPD.
Official title: Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Treatment of Orally Inhaled BI 1744 CL (3 - 4 Doses) Delivered by the Respimat® Inhaler in Patients With COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Asthma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-03-27
Enrollment: 409
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL inhalation solution delivered by the Respimat® inhaler for four weeks in patients with chronic obstructive pulmonary disease (COPD). The selection of the optimum dose(s) will be based on bronchodilator efficacy (how well it helps your breathing), safety evaluations and pharmacokinetic evaluations (the amount of the medication found in your blood).


Eligibility criteria: Inclusion Criteria:

1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions
2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:

   Patients must have relatively stable, moderate to severe airway obstruction with a post-bronchodilator FEV1 \&#61619; 30% of predicted normal and \< 80% of predicted normal and a post-bronchodilator FEV1 / FVC \< 70% at Visit 1
3. Male or female patients, 40 years of age or older
4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years. Patients who have never smoked cigarettes must be excluded
5. Patients must be able to perform technically acceptable pulmonary function tests and PEFR measurements, and must be able to maintain records (Patient Daily e-Diary) 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:

Selection of relevant exclusion criteria:

1. Patients with a history of asthma or a total blood eosinophil count 600/mm3.
2. Patients with any of the following conditions:

   * a diagnosis of thyrotoxicosis
   * a diagnosis of paroxysmal tachycardia (\>100 beats per minute)
   * a marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval \> 450 ms).
   * a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)
3. Patients with any of the following conditions:

   * a history of myocardial infarction within 1 year of screening visit (Visit 1)
   * a diagnosis of clinically relevant cardiac arrhythmia
   * 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
   * clinically evident bronchiectasis
   * a history of significant alcohol or drug abuse
4. Patients who have undergone thoracotomy with pulmonary resection
5. Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits
6. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the Screening Visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program
7. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1)
8. Pregnant or nursing women
9. Women of childbearing potential not using a highly effective method of birth control
10. Patients who have previously been randomized in this study or are currently participating in another study
11. Patients who are unable to comply with medication restrictions.

Primary outcomes:
measure: Trough FEV1 Response After 4 Weeks
timeFrame: Baseline and 4 weeks
Secondary outcomes:
measure: Trough FEV1 Response After 1 Week
timeFrame: Baseline and 1 week
measure: Trough FEV1 Response After 2 Weeks
timeFrame: Baseline and 2 weeks
measure: Trough FVC Response After 1 Week
timeFrame: Baseline and 1 week
measure: Trough FVC Response After 2 Weeks
timeFrame: Baseline and 2 weeks
measure: Trough FVC Response After 4 Weeks
timeFrame: Baseline and 4 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4
measure: Peak FEV1 (0-3h) Response After 4 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks
measure: Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4
measure: Peak FVC (0-3h) Response After 4 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at day 1
measure: Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 1
measure: Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 2
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 30 min, 1 h, 2 h, and 3 h relative to dose at day 1
measure: Peak FEV1 (0-3h) Response After 1 Weeks
timeFrame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 week
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 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1
timeFrame: baseline and day1
measure: Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week
timeFrame: Baseline and 1 week
measure: Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks
timeFrame: Baseline and 2 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks
timeFrame: Baseline and 4 weeks
measure: Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks
timeFrame: 4 weeks
measure: Weekly Mean Evening PEFR After 4 Weeks
timeFrame: 4 weeks
measure: Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks
timeFrame: 4 weeks
measure: Area Under Curve From 0 to 3 Hours (AUC0-3)
timeFrame: Baseline and 4 weeks
measure: Maximum Concentration (Cmax)
timeFrame: Baseline and 4 weeks
measure: Time From Dosing to the Maximum Concentration (Tmax)
timeFrame: Baseline and 4 weeks
measure: Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)
timeFrame: Baseline and 4 weeks
measure: Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)
timeFrame: Baseline and 4 weeks
measure: Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)
timeFrame: Baseline and 4 weeks
measure: Maximum Concentration at Steady State (Cmax,ss)
timeFrame: Baseline and 4 weeks
measure: Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
timeFrame: Baseline and 4 weeks
measure: Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
timeFrame: 4 weeks
measure: Laboratory Testing: Average Change From Baseline of Potassium
timeFrame: Baseline and day 29
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 1222.5.03 Boehringer Ingelheim Investigational Site
state: Alabama
city: Lakewood
country: United States
facility: 1222.5.07 Boehringer Ingelheim Investigational Site
state: California
city: Denver
country: United States
facility: 1222.5.14 Boehringer Ingelheim Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: 1222.5.17 Boehringer Ingelheim Investigational Site
state: Colorado
city: WheatRidge
country: United States
facility: 1222.5.13 Boehringer Ingelheim Investigational Site
state: Colorado
city: Stamford
country: United States
facility: 1222.5.18 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Panama City
country: United States
facility: 1222.5.15 Boehringer Ingelheim Investigational Site
state: Florida
city: Coeur D'Alene
country: United States
facility: 1222.5.04 Boehringer Ingelheim Investigational Site
state: Idaho
city: Shreveport
country: United States
facility: 1222.5.22 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Reno
country: United States
facility: 1222.5.11 Boehringer Ingelheim Investigational Site
state: Nevada
city: New York
country: United States
facility: 1222.5.24 Boehringer Ingelheim Investigational Site
state: New York
city: Raleigh
country: United States
facility: 1222.5.12 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Medford
country: United States
facility: 1222.5.10 Boehringer Ingelheim Investigational Site
state: Oregon
city: Hershey
country: United States
facility: 1222.5.05 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: 1222.5.02 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: 1222.5.08 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Charleston
country: United States
facility: 1222.5.19 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1222.5.06 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Kileen
country: United States
facility: 1222.5.21 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1222.5.01 Boehringer Ingelheim Investigational Site
state: Texas
city: Richmond
country: United States
facility: 1222.5.23 Boehringer Ingelheim Investigational Site
state: Virginia
city: Tacoma
country: United States
facility: 1222.5.20 Boehringer Ingelheim Investigational Site
state: Washington
city: Winnipeg
country: Canada
facility: 1222.5.039 St. Boniface General Hospital & Health Science Centre
state: Manitoba
city: Halifax
country: Canada
facility: 1222.5.032 Division of Respirology
state: Nova Scotia
city: Courtice
country: Canada
facility: 1222.5.038 Courtice Health Centre
state: Ontario
city: Kingston
country: Canada
facility: 1222.5.037 Kingston General Hospital
state: Ontario
city: Mississauga
country: Canada
facility: 1222.5.031 Alpha Medical Research Inc.
state: Ontario
city: Toronto
country: Canada
facility: 1222.5.034 Pulmonary Care Clinic and Research Centre
state: Ontario
city: Toronto
country: Canada
facility: 1222.5.040 Respiratory Research Lab
state: Ontario
city: Sherbrooke
country: Canada
facility: 1222.5.033 Centre de Recherche Clinique -CHUS
state: Quebec
city: Ste-Foy
country: Canada
facility: 1222.5.035 Hopital Laval
state: Quebec
city: Saskatoon
country: Canada
facility: 1222.5.036 Department of Respiratory Medicine
state: Saskatchewan
city: Berlin
country: Germany
facility: 1222.5.046 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.5.049 Boehringer Ingelheim Investigational Site
city: Gauting
country: Germany
facility: 1222.5.052 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 1222.5.051 Boehringer Ingelheim Investigational Site
city: Rüdersdorf
country: Germany
facility: 1222.5.047 Boehringer Ingelheim Investigational Site
city: Wiesbaden
country: Germany
facility: 1222.5.048 Boehringer Ingelheim Investigational Site
city: Almelo
country: Netherlands
facility: 1222.5.058 Boehringer Ingelheim Investigational Site
city: Breda
country: Netherlands
facility: 1222.5.056 Boehringer Ingelheim Investigational Site
city: Eindhoven
country: Netherlands
facility: 1222.5.059 Boehringer Ingelheim Investigational Site
city: Heerlen
country: Netherlands
facility: 1222.5.057 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Maleki-Yazdi MR, Beck E, Hamilton AL, Korducki L, Koker P, Fogarty C. A randomised, placebo-controlled, Phase II, dose-ranging trial of once-daily treatment with olodaterol, a novel long-acting beta2-agonist, for 4 weeks in patients with chronic obstructive pulmonary disease. Respir Med. 2015 May;109(5):596-605. doi: 10.1016/j.rmed.2015.02.012. Epub 2015 Mar 3.