Clinical trial NCT00846768: BI 1744 CL With Respimat Once Daily Versus Twice Daily in COPD
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-02-19
Enrollment: 47
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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 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
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
5. Patients must be able to perform technically acceptable pulmonary function tests
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:

1. Patients with a significant disease other than COPD.
2. 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.
3. 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.
4. Patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period.
5. Patients with any of the following conditions: a diagnosis of thyrotoxicosis; a diagnosis of paroxysmal tachycardia (\>100 beats per minute)
6. 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
7. Patients who have undergone thoracotomy with pulmonary resection
8. 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.
9. Patients who regularly use daytime oxygen therapy for more than one hour per day.
10. 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
11. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit
12. Patients with known hypersensitivity to beta-adrenergics drugs, BAC, EDTA or any other component of the Respimat inhalation solution delivery system
13. Pregnant or nursing women
14. Women of childbearing potential not using two effective methods of birth control (one barrier, 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
15. Patients who have previously been randomized in this study or are currently participating in another study
16. Patients who are unable to comply with pulmonary medication restrictions prior to randomization

Primary outcomes:
measure: FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment
timeFrame: 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
measure: FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment
timeFrame: 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
Secondary outcomes:
measure: FEV1 Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment
timeFrame: 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
measure: Peak FEV1 (0-3h) Response After 3 Weeks
timeFrame: Baseline, 3 weeks
measure: Trough FEV1 Response
timeFrame: Baseline, 3 weeks
measure: FVC Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment
timeFrame: 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
measure: FVC Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment
timeFrame: 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
measure: FVC Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment
timeFrame: 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
measure: Peak FVC (0-3h) Response After 3 Weeks
timeFrame: Baseline, 3 weeks
measure: Trough FVC Response
timeFrame: Baseline, 3 weeks
measure: Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination
timeFrame: 3 weeks
measure: Pharmacokinetics (PK): Concentration of the Analyte in Plasma Measured at 0.167 Hours Post Dosing at Steady State
timeFrame: 3 weeks
measure: Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 12 Hours
timeFrame: 3 weeks
measure: Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 24 Hours
timeFrame: 3 weeks
measure: Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 12 Hours
timeFrame: 3 weeks
measure: Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 24 Hours
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Genk
country: Belgium
facility: 1222.26.32008 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1222.26.32006 Boehringer Ingelheim Investigational Site
city: Hasselt
country: Belgium
facility: 1222.26.32007 Boehringer Ingelheim Investigational Site
city: Eindhoven
country: Netherlands
facility: 1222.26.31002 Boehringer Ingelheim Investigational Site
city: Heerlen
country: Netherlands
facility: 1222.26.31001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Joos GF, Aumann JL, Coeck C, Korducki L, Hamilton AL, Kunz C, Aalbers R. A randomised, double-blind, four-way, crossover trial comparing the 24-h FEV1 profile for once-daily versus twice-daily treatment with olodaterol, a novel long-acting beta2-agonist, in patients with chronic obstructive pulmonary disease. Respir Med. 2015 May;109(5):606-15. doi: 10.1016/j.rmed.2015.02.005. Epub 2015 Feb 14.