Randomised, Double-Blind, Cross-over Study to Determine the 24-hour FEV1-time Profile of Orally Inhaled BI 1744 CL, Delivered With the Respimat Inhaler, After 3 Weeks of Once Daily or Twice Daily Administration in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Boehringer Ingelheim5 sites in 2 countries47 target enrollmentFebruary 2009

ConditionsPulmonary Disease, Chronic Obstructive

DrugsBI 1744 CL

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: Boehringer Ingelheim
Enrollment: 47
Locations: 5
Primary Endpoint: FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of the trial is to determine the effect of BI 17444Cl on the lung function over a 24-hour period, when it is inhaled using the Respimat inhaler in patients with chronic obstructive pulmonary disease. In the trial four treatments of each 3 weeks of duration are included: 2 dosages in a once daily administration and 2 dosages for administration twice daily.

Registry

clinicaltrials.gov

Start Date

February 2009

End Date

July 2009

Last Updated

11 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Eligibility Criteria

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 COPD and must meet the following spirometric criteria:
•Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 \< 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
•Patients must be able to inhale medication in a competent manner from the Respimat inhaler and from a metered dose inhaler (MDI).

Exclusion Criteria

•Patients with a significant disease other than COPD.
•Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT \> x2 ULN, SGPT \> x2 ULN, bilirubin \> x2 ULN or creatinine \> x2 ULN will be excluded regardless of clinical condition.
•Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma. If a patient has a total blood eosinophil count more than 600/mm3, source documentation is required to verify that the increased eosinophil count is related to a non-asthmatic condition.
•Patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period.
•Patients with any of the following conditions: a diagnosis of thyrotoxicosis; a diagnosis of paroxysmal tachycardia (\>100 beats per minute)
•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; clinically evident bronchiectasis; a history of significant alcohol or drug abuse
•Patients who have undergone thoracotomy with pulmonary resection
•Patients being treated with any of the following concomitant medications: oral beta2-adrenergics; oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.
•Patients who regularly use daytime oxygen therapy for more than one hour per day.
•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

Outcomes

Primary Outcomes

FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment

Time Frame: Day 0: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to planned evening dose on day 1; Day 21: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to evening dose

Response was defined as change from baseline. Baseline FEV1 AUC (12-24) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment

Time Frame: Day 0: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to planned morning dose on day 1; Day 21: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to morning dose

Response was defined as change from baseline. Baseline FEV1 AUC (0-12) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

Secondary Outcomes

Trough FVC Response(Baseline, 3 weeks)
Pharmacokinetics (PK): Concentration of the Analyte in Plasma Measured at 0.167 Hours Post Dosing at Steady State(3 weeks)
Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 24 Hours(3 weeks)
Peak FEV1 (0-3h) Response After 3 Weeks(Baseline, 3 weeks)
Peak FVC (0-3h) Response After 3 Weeks(Baseline, 3 weeks)
FEV1 Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment(Day0:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to planned morning dose on day1,0:30,1,2,10,11,11:50h relative to planned evening dose on day1; Day21:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to morning dose,0:30,1,2,10,11,11:50h relative to evening dose)
Trough FEV1 Response(Baseline, 3 weeks)
FVC Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment(Day 0: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to planned evening dose on day 1; Day 21: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to evening dose)
Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 24 Hours(3 weeks)
Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 12 Hours(3 weeks)
Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 12 Hours(3 weeks)
FVC Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment(Day 0: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to planned morning dose on day 1; Day 21: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to morning dose)
FVC Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment(Day0:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to planned morning dose on day1, 0:30,1,2,10,11,11:50h relative to planned evening dose on day1; Day21:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to morning dose,0:30,1,2,10,11,11:50h relative to evening dose)
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination(3 weeks)