A randomised, double-blind, 8 treatments, 4 periods, incomplete crossoverstudy to determine the optimal free dose combination ofBI 1744 CL and tiotropium bromide (both delivered by the Respimat®Inhaler) after 4 weeks once daily treatment in patients with COPD

• Conditions: Chronic Obstructive Pulmonary Disease (COPD); MedDRA version: 12.0Level: LLTClassification code 10010952Term: COPD

• Registration Number: EUCTR2009-014880-38-SE
• Lead Sponsor: Boehringer Ingelheim AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-16
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 224

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 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
4. Male or female patients, 40 years of age or older.
5. Patients must be current or ex-smokers with a smoking history of more than 10 pack-years.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patients with a significant disease other than COPD
2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
3. Patients with a history of asthma or a total blood eosinophil count =600/mm3.
4. Patients with any of the following conditions:
– a diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists)
– a diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known
class side effect profile of ß2-agonists)
– a marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration
of a QTcF* interval >450 ms) (*Fredericia correction)
– a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure,
hypokalemia, family history of Long QT Syndrome)
5. 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 (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
6. Patients who have undergone thoracotomy with pulmonary resection (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1)
7. Patients being treated with any of the following concomitant medications:
– medications that prolong the QT/QTc interval
– oral ß-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
8. 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.
9. 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.
10. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1)
11. Pregnant or nursing women
12. Women of childbearing potential not using two effective methods of birth control

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Determine the optimum once daily dose of BI 1744 CL (5 ug, 10 ug) and<br>tiotropium (1.25, 2.5 and 5.0 ug) in free dose combination (delivered by the<br>Respimat® inhaler) after four week treatment in patients with COPD;Secondary Objective: Efficacy endpoints<br>1. Trough FVC (forced vital capacity) response [L] after 4 weeks of treatment<br>2. FEV1, FVC and PEF AUC0-3h, , AUC0-6h and peak0-3h response [L] after<br>4 weeks of treatment<br>3. FEV1, FVC and PEF AUC0-3h and peak0-3h response [L] after the first dose.<br>4. Individual FEV1, FVC and PEF measurements [L] at each time point<br>5. Weekly mean number of puffs of rescue medication used per day (PRN<br>salbutamol (albuterol))<br>6. Physician’s Global Evaluation<br>7. Patient’s Global Rating<br>2.3.2 Safety endpoints<br>1. Adverse events<br>2. Pulse rate and blood pressure (seated) recorded in conjunction with spirometry<br>(30 minutes post dose only);Primary end point(s): trough FEV1 response [L] after four weeks of treatment.