Clinical trial NCT00720499: Efficacy and Safety of 4 Weeks of Treatment With Orally Inhaled BI1744/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-07-22
Enrollment: 141
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).


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 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
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 and PEF measurements, and must be able to maintain records (Patient Daily e-Diary) during the study period as required in the protocol
6. Patients must be able to inhale medication in a competent manner from the Respimat inhaler and from a metered dose inhaler (MDI).
7. additional inclusion criteria apply.

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, 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)
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, 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
7. 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.
8. Pregnant or nursing women
9. 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
10. Patients who have previously been randomized in this study or are currently participating in another study
11. Patients who are unable to comply with pulmonary medication restrictions prior to randomization
12. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit
13. additional exclusion criteria apply.

Primary outcomes:
measure: Trough Forced Expiratory Volume in One Second (FEV1) Response [L] After Four Weeks of Treatment.
timeFrame: 1 hour (h), 10 minutes (min) before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
Secondary outcomes:
measure: Trough FEV1 Response [L] After 2 Weeks of Treatment
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15
measure: Individual FEV1 Measurements
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
measure: FEV1 AUC 0-3h, Response
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
measure: FEV1 Peak 0-3h Response
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
measure: FEV1, AUC (0-6h) Response
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
measure: FEV1 (Unsupervised) AUC (6-12h) Response
timeFrame: 6 hours (h), 9h and 12h after drug administration on day 29
measure: Trough FVC Response
timeFrame: 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
measure: Individual FVC Measurements
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
measure: FVC AUC (0-3h) Response
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
measure: FVC AUC (0-6h) Response
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
measure: FVC Peak 0-3h Response
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 29
measure: PEFR AUC (0-3h) Response
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
measure: PEFR Peak 0-3h Response
timeFrame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
measure: PEFR AUC (6-12h) Response
timeFrame: 1 hour (h) and 10 minutes before drug administration on day 1 and 6h, 9h and 12h after drug administration on day 29
measure: Weekly Mean Morning PEFR
timeFrame: Weeks 1,2,3 and 4
measure: Weekly Mean Evening PEFR
timeFrame: Weeks 1,2,3 and 4
measure: Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol])
timeFrame: Weeks 1,2,3 and 4
measure: Patient Global Rating
timeFrame: 4 weeks
measure: Physician's Global Evaluation
timeFrame: Days 15 and 29
measure: Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination
timeFrame: 14 weeks
measure: Overall Marked Changes From Baseline in Vital Signs
timeFrame: Baseline to week 14
measure: 12-lead ECG Heart Rate
timeFrame: 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
measure: 12-lead ECG PR Intervals
timeFrame: 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
measure: 12-lead ECG QRS Intervals
timeFrame: 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
measure: 12-lead ECG QTcF Intervals
timeFrame: 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
measure: 12-lead ECG QTcB Intervals
timeFrame: 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
measure: 12-lead ECG QT Intervals
timeFrame: 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
measure: 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)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: 1237.9.00152 Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: 1237.9.00155 Boehringer Ingelheim Investigational Site
state: Florida
city: Philadelphia
country: United States
facility: 1237.9.00151 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Killeen
country: United States
facility: 1237.9.00154 Boehringer Ingelheim Investigational Site
state: Texas
city: Spokane
country: United States
facility: 1237.9.00153 Boehringer Ingelheim Investigational Site
state: Washington
city: Brussel
country: Belgium
facility: 1237.9.03253 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1237.9.03255 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1237.9.03254 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1237.9.03251 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1237.9.03252 Boehringer Ingelheim Investigational Site
city: Mississauga
country: Canada
facility: 1237.9.00255 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1237.9.00251 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1237.9.00252 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1237.9.00254 Boehringer Ingelheim Investigational Site
state: Ontario
city: Ste-Foy
country: Canada
facility: 1237.9.00253 Boehringer Ingelheim Investigational Site
state: Quebec
city: Berlin
country: Germany
facility: 1237.9.04952 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1237.9.04953 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1237.9.04954 Boehringer Ingelheim Investigational Site
city: Bruchsal
country: Germany
facility: 1237.9.04955 Boehringer Ingelheim Investigational Site
city: Gelnhausen
country: Germany
facility: 1237.9.04959 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 1237.9.04960 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1237.9.04958 Boehringer Ingelheim Investigational Site
city: Tübingen
country: Germany
facility: 1237.9.04951 Boehringer Ingelheim Investigational Site
city: Wiesloch
country: Germany
facility: 1237.9.04956 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: