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

Phase 2CompletedNCT00720499

Boehringer Ingelheim141 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

141

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

BI 1744 CL plus tiotropium bromideDRUG

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

Respimat® InhalerDEVICE

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

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.

Locations (24)

Outcomes

Primary Outcomes

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

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).

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

Secondary Outcomes

Trough FEV1 Response [L] After 2 Weeks of Treatment

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).

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

Individual FEV1 Measurements

Individual FEV1 measurements \[L\] at each time point on Day 29. The presented means are adjusted.

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

FEV1 AUC 0-3h, Response

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).

Data from ClinicalTrials.gov

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1237.9.00152 Boehringer Ingelheim Investigational Site

Clearwater, Florida, United States

1237.9.00155 Boehringer Ingelheim Investigational Site

Tampa, Florida, United States

1237.9.00151 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

1237.9.00154 Boehringer Ingelheim Investigational Site

Killeen, Texas, United States

1237.9.00153 Boehringer Ingelheim Investigational Site

Spokane, Washington, United States

1237.9.03253 Boehringer Ingelheim Investigational Site

Brussels, Belgium

1237.9.03255 Boehringer Ingelheim Investigational Site

Brussels, Belgium

1237.9.03254 Boehringer Ingelheim Investigational Site

Edegem, Belgium

1237.9.03251 Boehringer Ingelheim Investigational Site

Ghent, Belgium

1237.9.03252 Boehringer Ingelheim Investigational Site

Leuven, Belgium

...and 14 more locations

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

FEV1 Peak 0-3h Response

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).

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

FEV1, AUC (0-6h) Response

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).

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

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

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).

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

Trough FVC Response

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).

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

Individual FVC Measurements

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.

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

FVC AUC (0-3h) Response

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).

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

FVC AUC (0-6h) Response

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).

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

FVC Peak 0-3h Response

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).

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

PEFR AUC (0-3h) Response

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).

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

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).

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

PEFR AUC (6-12h) Response

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).

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

Weekly Mean Morning PEFR

Weekly mean morning PEFR \[L/min\] on weeks 1,2,3 and 4. The presented means are adjusted.

Time frame: Weeks 1,2,3 and 4

Weekly Mean Evening PEFR

Weekly mean evening PEFR \[L/min\] on weeks 1,2,3 and 4. The presented means are adjusted.

Time frame: Weeks 1,2,3 and 4

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

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.

Time frame: Weeks 1,2,3 and 4

Patient Global Rating

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.

Time frame: 4 weeks

Physician's Global Evaluation

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

Time frame: Days 15 and 29

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

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

Time frame: 14 weeks

Overall Marked Changes From Baseline in Vital Signs

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

Time frame: Baseline to week 14

12-lead ECG Heart Rate

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.