Clinical trial NCT00467740: Efficacy and Safety of 4 Weeks of Treatment With Inhaled BI 1744 CL in Patients With Asthma
Official title: Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy (Bronchodilation) and Safety of 4 Weeks of Treatment of Orally Inhaled BI 1744 CL (4 Doses) Delivered by the Respimat® Inhaler in Patients With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-05-01
Enrollment: 296
Sex: ALL
Minimum age (years): 18
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 asthma. 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. Male or female patients, 18 years of age or older
3. Diagnosis of asthma (GINA)
4. Pre-bronchodilator FEV1 greater than or equal to 60% predicted and \<90% predicted (ECSC);
5. Increase in FEV1 greater than or equal to 12% and 200 ml 15 minutes after 400µg salbutamol (albuterol) at Visit 1
6. Patient must have been taking Inhaled Corticosteroids for at least 12 weeks prior to screening, and must have been receiving a stable low/moderate dose for at least 6 weeks prior to screening.
7. Patients must be able to perform technically acceptable pulmonary function tests and PEF measurements, and must be able to maintain records (Patient Daily e-Diary) during the study period as required in the protocol
8. 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 a smoking history of more than 10 pack years
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, a history of cor pulmonale, 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 have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1)
6. Pregnant or nursing women
7. Women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least 2 years
8. Patients who have previously been randomized in this study or are currently participating in another study
9. Patients who are unable to comply with pulmonary medication restrictions prior to randomization

Primary outcomes:
measure: Trough FEV1 Response After 4 Weeks
timeFrame: Baseline and 4 weeks
Secondary outcomes:
measure: Weekly Mean Pre-dose Morning PEFR After 4 Weeks
timeFrame: Baseline and 4 weeks
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: 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: 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: Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) 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 relative to dose at Week 4
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 Week
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: 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: Peak FVC (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 after 1 weeks
measure: Peak FVC (0-3h) Response After 1 Week
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 weeks
measure: Peak FVC (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: 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 6-12 h (AUC 6-12h) Response at Week 4
timeFrame: 1 hour (h) prior to dose on first day of randomized treatment (baseline) and 1h, 3h, 6h, 9h, 12h relative to dose at Week 4
measure: Weekly Mean Evening PEFR After 4 Weeks
timeFrame: Baseline and 4 weeks
measure: PEFR Variability 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: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration
measure: Maximum Concentration (Cmax)
timeFrame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration
measure: Time From Dosing to the Maximum Concentration (Tmax)
timeFrame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration
measure: Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)
timeFrame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
measure: Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)
timeFrame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
measure: Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)
timeFrame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
measure: Maximum Concentration at Steady State (Cmax,ss)
timeFrame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
measure: Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
timeFrame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
measure: Total Score in Asthma Control Questionnaire After 4 Weeks
timeFrame: 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 29 days
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: 1222.6.064 Arthur F. Gelb Medical Corporation, Lakewood
state: California
city: Los Angeles
country: United States
facility: 1222.6.062 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1222.6.066 Allergy & Asthma Medical Group and Rsrch Ctr, APC
state: California
city: San Diego
country: United States
facility: 1222.6.069 Allergy Associates Medical Group
state: California
city: Denver
country: United States
facility: 1222.6.068 National Jewish Medical Center
state: Colorado
city: Wheat Ridge
country: United States
facility: 1222.6.073 Boehringer Ingelheim Investigational Site
state: Colorado
city: North Darthmouth
country: United States
facility: 1222.6.067 Northeast Medical Research Associates, Inc
state: Massachusetts
city: Winston-Salem
country: United States
facility: 1222.6.061 Center for Human Genomics
state: North Carolina
city: Kileen
country: United States
facility: 1222.6.072 Boehringer Ingelheim Investigational Site
state: Texas
city: Tacoma
country: United States
facility: 1222.6.071 Pulmonary Consultants
state: Washington
city: Calgary
country: Canada
facility: 1222.6.017 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 1222.6.006 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: 1222.6.012 Boehringer Ingelheim Investigational Site
state: Manitoba
city: Winnipeg
country: Canada
facility: 1222.6.016 Boehringer Ingelheim Investigational Site
state: Manitoba
city: Hamilton
country: Canada
facility: 1222.6.011 Boehringer Ingelheim Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: 1222.6.003 Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: 1222.6.013 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1222.6.005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1222.6.009 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1222.6.008 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 1222.6.015 Boehringer Ingelheim Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: 1222.6.007 Boehringer Ingelheim Investigational Site
state: Quebec
city: Ste-Foy
country: Canada
facility: 1222.6.002 Boehringer Ingelheim Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: 1222.6.004 Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Bethune Cedex
country: France
facility: 1222.6.3303A Boehringer Ingelheim Investigational Site
city: Briancon
country: France
facility: 1222.6.3308A Boehringer Ingelheim Investigational Site
city: Grenoble
country: France
facility: 1222.6.3302A Boehringer Ingelheim Investigational Site
city: Lille
country: France
facility: 1222.6.3306A Boehringer Ingelheim Investigational Site
city: Montpellier
country: France
facility: 1222.6.3301A Boehringer Ingelheim Investigational Site
city: Nîmes
country: France
facility: 1222.6.3304A Boehringer Ingelheim Investigational Site
city: Saint-Pierre Cedex - La Réunion
country: France
facility: 1222.6.3305A Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.6.031 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.6.034 Boehringer Ingelheim Investigational Site
city: Gauting
country: Germany
facility: 1222.6.037 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1222.6.038 Boehringer Ingelheim Investigational Site
city: Rüdersdorf
country: Germany
facility: 1222.6.032 Boehringer Ingelheim Investigational Site
city: Wiesloch
country: Germany
facility: 1222.6.036 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: O'Byrne PM, D'Urzo T, Beck E, Flezar M, Gahlemann M, Hart L, Blahova Z, Toorawa R, Beeh KM. Dose-finding evaluation of once-daily treatment with olodaterol, a novel long-acting beta2-agonist, in patients with asthma: results of a parallel-group study and a crossover study. Respir Res. 2015 Aug 18;16(1):97. doi: 10.1186/s12931-015-0249-8.