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Completed

NCT Number: NCT00720499

Efficacy and Safety of 4 Weeks of Treatment With Orally Inhaled BI1744/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease (COPD)

The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL administered with 5 microgram tiotropium bromide solution for inhalation, delivered by the Respimat® inhaler, once daily for four weeks in patients with chronic obstructive pulmonary disease (COPD).

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Key information

Conditions

Pulmonary Disease, Chronic Obstructive Chronic Disease Disease Attributes Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

1237.9.03253 Boehringer Ingelheim Investigational Site, Brussels, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 >= 30% of predicted normal and <80% of predicted normal and a post-bronchodilator FEV1 / FVC <70% at Visit 1

  • 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
  • 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
  • Patients must be able to inhale medication in a competent manner from the Respimat inhaler and from a metered dose inhaler (MDI).
  • additional inclusion criteria apply.

Exclusion criteria

  • Patients with a significant disease other than COPD
  • Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
  • Patients with a history of asthma or a total blood eosinophil count >= 600/mm3.
  • 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 QTcF* 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)
  • 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, a history of life-threatening pulmonary obstruction, a history of cystic fibrosis, clinically evident bronchiectasis, a history of significant alcohol or drug abuse
  • Patients who have undergone thoracotomy with pulmonary resection
  • 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.
  • Pregnant or nursing women
  • Women of childbearing potential not using two effective method of birth control (one barrier and one non-barrier). 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 two years
  • Patients who have previously been randomized in this study or are currently participating in another study
  • Patients who are unable to comply with pulmonary medication restrictions prior to randomization
  • Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit
  • additional exclusion criteria apply.

Treatment and study plan

BI 1744 CL plus tiotropium bromide

Drug

BI 1744 CL plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation

Respimat® Inhaler

Device

Primary outcomes

  1. Trough Forced Expiratory Volume in One Second (FEV1) Response [L] After Four Weeks of Treatment.

    Time frame: 1 hour (h), 10 minutes (min) before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

    Trough FEV1 was defined as the mean of the 2 FEV1 values at the end of the dosing interval, 24 hours post-drug administration.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Secondary outcomes

  1. Trough FEV1 Response [L] After 2 Weeks of Treatment

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  2. Individual FEV1 Measurements

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

    Individual FEV1 measurements [L] at each time point on Day 29.

    The presented means are adjusted.

  3. FEV1 AUC 0-3h, Response

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

    FEV1 Area Under the Curve (AUC) 0-3h, response [L] on days 1, 15 and 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  4. FEV1 Peak 0-3h Response

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

    FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response [L] on days 1, 15 and 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  5. FEV1, AUC (0-6h) Response

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

    FEV1, AUC (0-6h) response [L] on day 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  6. FEV1 (Unsupervised) AUC (6-12h) Response

    Time frame: 6 hours (h), 9h and 12h after drug administration on day 29

    FEV1 (unsupervised) AUC (6-12h) response [L] on day 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  7. Trough FVC Response

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15, in addition 4h, 5h, 6h after drug administration on day 29

    Trough Forced Vital Capacity (FVC) response [L] on days 15 and 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  8. Individual FVC Measurements

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

    Individual FVC measurements [L] at each time point

    The categories correspond to the planned times for FVC measurements on Day 29.

    The presented means are adjusted.

  9. FVC AUC (0-3h) Response

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

    FVC AUC (0-3h) response [L] on days 1, 15 and 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  10. FVC AUC (0-6h) Response

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

    FVC AUC (0-6h) response [L] on day 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  11. FVC Peak 0-3h Response

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 29

    FVC peak 0-3h response [L] on day 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  12. PEFR AUC (0-3h) Response

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

    Peak Expiratory Flow Rate (PEFR) AUC (0-3h) response [L/min] on days 1, 15 and 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  13. PEFR Peak 0-3h Response

    Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

    PEFR peak 0-3h response [L/min] on days 1, 15 and 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  14. PEFR AUC (6-12h) Response

    Time frame: 1 hour (h) and 10 minutes before drug administration on day 1 and 6h, 9h and 12h after drug administration on day 29

    PEFR AUC (6-12h) response [L] on day 29.

    Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

    The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

  15. Weekly Mean Morning PEFR

    Time frame: Weeks 1,2,3 and 4

    Weekly mean morning PEFR [L/min] on weeks 1,2,3 and 4.

    The presented means are adjusted.

  16. Weekly Mean Evening PEFR

    Time frame: Weeks 1,2,3 and 4

    Weekly mean evening PEFR [L/min] on weeks 1,2,3 and 4.

    The presented means are adjusted.

  17. Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol])

    Time frame: Weeks 1,2,3 and 4

    Weekly mean number of occasions of rescue therapy used per day (as occasion require (PRN) salbutamol [albuterol]) on weeks 1,2,3 and 4.

    The means presented are the adjusted mean of weekly mean.

  18. Patient Global Rating

    Time frame: 4 weeks

    Patient global rating scores treatment comparison after 4 weeks

    The score was evaluated on a 7-point scale :

    • 1 : very much better
    • 2 : much better
    • 3 : a little better
    • 4 : no change
    • 5 : a little worse
    • 6 : much worse
    • 7 : very much worse

    The presented means are adjusted.

  19. Physician's Global Evaluation

    Time frame: Days 15 and 29

    Physician's global evaluation score on days 15 and 29

    The score was evaluated on a 8-points scale :

    • Poor : 1,2
    • Fair : 3,4
    • Good : 5,6
    • Excellent : 7,8

    The presented means are adjusted

  20. Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination

    Time frame: 14 weeks

    Clinically significant abnormalities for blood chemistry, haematology, urinalysis and physical examination

  21. Overall Marked Changes From Baseline in Vital Signs

    Time frame: Baseline to week 14

    Overall marked changes from baseline in systolic blood pressure, diastolic blood pressure and pulse rate.

  22. 12-lead ECG Heart Rate

    Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

    12-lead Electrocardiogram (ECG) Heart rate baseline and change from baseline values at other time points in Beats Per Minute (BPM)

    Statistics for each planned time from baseline to day 29.

  23. 12-lead ECG PR Intervals

    Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

    12-lead ECG PR intervals baseline and change from baseline at other timepoints in milliseconds.

    Statistics for each planned time from baseline to day 29.

  24. 12-lead ECG QRS Intervals

    Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

    12-lead ECG QRS intervals baseline and change from baseline at other time points in milliseconds

    Statistics for each planned time from baseline to day 29.

  25. 12-lead ECG QTcF Intervals

    Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

    12-lead ECG corrected heart rate (QT) interval, using Fridericia method (QTcF), baseline and change from baseline at other time points in milliseconds.

    Statistics for each planned time from baseline to day 29.

  26. 12-lead ECG QTcB Intervals

    Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

    12-lead ECG heart rate corrected QT interval, using Bazett method (QTcB), baseline and change from baseline at other time points in milliseconds.

    Statistics for each planned time from baseline to day 29.

  27. 12-lead ECG QT Intervals

    Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

    12-lead ECG QT intervals baseline and change from baseline at other time points in milliseconds.

    Statistics for each planned time from baseline to day 29.

  28. AUC (0-6H) FEV1 (Unsupervised), AUC (0-6H) PEFR (Unsupervised), FVC Peak (0-3h), AUC (6-12h) FEV1 (Unsupervised), AUC (6-12h) PEFR (Unsupervised), Individual PEFR Measurements (Supervised and Unsupervised), Individual PEFR Measurements (Unsupervised)

    Time frame: 4 weeks

    • AUC (0-6h) for FEV1, and PEFR (unsupervised) after first dose and after 2 and 4 weeks of treatment were not analysed in the study report because the pertinent information from the unsupervised Pulmonary Function Tests (PFTs) was for the time interval from 6 to 12 hours post-dosing.
    • FVC peak 0-3h response after the first dose and at Week 2 (supervised) and AUC (6-12h) for FEV1 and PEFR after the first dose and at Week 2 (unsupervised) were not analysed in the study report.
    • Individual PEFR (supervised) measurements and individual FEV1 and PEFR (unsupervised) measurements at each time point were not analysed in the study report.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

Randomised, Double-blind, Cross-over Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of 2 Doses of Orally Inhaled BI 1744 CL, Each in Fixed Dose Combination (FDC) With 5 Microgram Tiotropium Bromide (Delivered by the Respimat® Inhaler) in Patients With COPD

Important dates

Study start
2008
Primary completion
2009
First posted
Jul 22, 2008
Registry last updated
Aug 17, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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