Efficacy and Safety of 4 Weeks of Treatment With Inhaled BI 1744 CL in Patients With Asthma

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00467740
First received: April 30, 2007
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Asthma
Drug: BI 1744 CL
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Trough FEV1 Response After 4 Weeks [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.


Secondary Outcome Measures:
  • Weekly Mean Pre-dose Morning PEFR After 4 Weeks [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Baseline peak expiratory flow response (PEFR) was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment.

  • Trough FEV1 Response After 1 Week [ Time Frame: Baseline and 1 week ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.

  • Trough FEV1 Response After 2 Weeks [ Time Frame: Baseline and 2 weeks ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.

  • Trough FVC Response After 1 Week [ Time Frame: Baseline and 1 week ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.

  • Trough FVC Response After 2 Weeks [ Time Frame: Baseline and 2 weeks ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.

  • Trough FVC Response After 4 Weeks [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.

  • Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.

  • Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. FVC AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.

  • Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

  • Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

  • Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

  • Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 4 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

  • Peak FEV1 (0-3h) Response At Day 1 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.

  • Peak FEV1 (0-3h) Response After 1 Week [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.

  • Peak FEV1 (0-3h) Response After 2 Weeks [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.

  • Peak FEV1 (0-3h) Response After 4 Weeks [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.

  • Peak FVC (0-3h) Response At Day 1 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment.

  • Peak FVC (0-3h) Response After 1 Week [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment.

  • Peak FVC (0-3h) Response After 2 Weeks [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment.

  • Peak FVC (0-3h) Response After 4 Weeks [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment.

  • Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

  • Weekly Mean Evening PEFR After 4 Weeks [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    Response was defined as change from baseline. Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment.

  • PEFR Variability After 4 Weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    PEFR variability represents the absolute difference between the highest morning PEFR value and the highest evening PEFR value of 1 day, divided by the arithmetic mean of these 2 PEFR values and expressed as a percent, weekly means.

  • Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Weekly mean number of occasions of rescue therapy used per day (prn salbutamol [albuterol]) as assessed by the e-Diary (e-Diary incorporated in AM2+).

  • Area Under Curve From 0 to 3 Hours (AUC0-3) [ Time Frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration ] [ Designated as safety issue: No ]
    AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=3

  • Maximum Concentration (Cmax) [ Time Frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration ] [ Designated as safety issue: No ]
    Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.

  • Time From Dosing to the Maximum Concentration (Tmax) [ Time Frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration ] [ Designated as safety issue: No ]
    tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.

  • Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) [ Time Frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration ] [ Designated as safety issue: No ]
    AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=3 at steady state.

  • Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) [ Time Frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration ] [ Designated as safety issue: No ]
    AUC0-6,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=6 at steady state.

  • Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss) [ Time Frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration ] [ Designated as safety issue: No ]
    AUC0-24,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=24 at steady state.

  • Maximum Concentration at Steady State (Cmax,ss) [ Time Frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration ] [ Designated as safety issue: No ]
    Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state.

  • Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) [ Time Frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration ] [ Designated as safety issue: No ]
    tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state.

  • Total Score in Asthma Control Questionnaire After 4 Weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Adequacy of asthma control was assessed using a scale of: 0=totally controlled, to 6=Severely uncontrolled.

  • Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Clinical relevant abnormalities for vital signs, ECG and physical examination. Any new or clinically relevant worsening of baseline conditions was reported as adverse events.

  • Laboratory Testing: Average Change From Baseline of Potassium [ Time Frame: Baseline and 29 days ] [ Designated as safety issue: No ]
    Laboratory testing: Average change from baseline of potassium measured on test-days. Pre−dose value on test day 1 is the baseline value.


Enrollment: 296
Study Start Date: May 2007
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00467740

  Show 37 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00467740     History of Changes
Other Study ID Numbers: 1222.6, EUDRACT 2006-004829-29
Study First Received: April 30, 2007
Results First Received: March 28, 2014
Last Updated: June 17, 2014
Health Authority: Canada: Therapeutic Products Directorate
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Germany: BfArM Bundesinstitut fuer Arzneimittel und Medizinprodukte
United States: Food and Drug Administration

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on August 28, 2014