Characterization of 24 Hour Spirometry Profiles of Inhaled BI 1744 CL and Inhaled Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease

Boehringer Ingelheim108 enrolled

Overview

The study is intended to characterize the lung function profile of BI1744 in COPD patients where patients will perform pulmonary function tests at regular intervals for 24 hours at the end of a 6 week treatment period. Each patient will receive all four treatments.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

108

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Olodaterol (BI1744) LowDRUG

Low dose inhaled orally once daily from Respimat inhaler

Placebo (for olodaterol BI1744)DRUG

Placebo (olodaterol low and high dose)delivered by Respimat

Placebo (for Tiotropium)DRUG

Placebo (Tiotropium 18 mcg) delivered by HandiHaler

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion criteria: * Patients willing to participate with confirmed diagnosis of COPD * 40 years of age or older * having a 10 pack year smoking history * able to perform serial pulmonary function tests * able to use both a Dry powder inhaler (DPI) and Respimat device Exclusion criteria: * Significant other disease * clinically relevant abnormal hematology, chemistry, or urinalysis * history of asthma * diagnosis of thyrotoxicosis * paroxysmal tachycardia related to beta agonists * history of MI within 1 year, cardiac arrhythmia, hospitalization for heart failure within 1 year * active tuberculosis, cystic fibrosis, clinically evident bronchiectasis * significant alcohol or drug abuse * pulmonary resection * taking oral beta adrenergics * taking unstable oral steroids * daytime oxygen * enrolled in rehabilitation program * enrolled in another study or taking investigational products * pregnant or nursing women, women of child bearing potential not willing to use two methods of birth control * those who are not willing to comply with pulmonary medication washouts

Locations (15)

1222.39.32003 Boehringer Ingelheim Investigational Site

Genk, Belgium

1222.39.32001 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Outcomes

Primary Outcomes

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

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit for the first period, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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.

Time frame: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of the first treatment period (study baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 12 h relative to am dose after six weeks of treatment

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

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit for the first period, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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.

Time frame: 1 h and 10 min prior to am dose on the first day of the first treatment period (study baseline) and 12 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

Secondary Outcomes

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the first visit of the first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.

Data from ClinicalTrials.gov

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High dose inhaled orally once daily from Respimat inhaler

Tiotropium 18 mcgDRUG

18mcg inhaled once daily from Handihaler

1222.39.32002 Boehringer Ingelheim Investigational Site

Hasselt, Belgium

1222.39.45001 Boehringer Ingelheim Investigational Site

Hvidovre, Denmark

1222.39.45003 Boehringer Ingelheim Investigational Site

Kolding, Denmark

1222.39.45002 Boehringer Ingelheim Investigational Site

Odense C, Denmark

1222.39.49391 Boehringer Ingelheim Investigational Site

Berlin, Germany

1222.39.49392 Boehringer Ingelheim Investigational Site

Hamburg, Germany

1222.39.49393 Boehringer Ingelheim Investigational Site

Mannheim, Germany

1222.39.36006 Boehringer Ingelheim Investigational Site

Deszk, Hungary

...and 5 more locations

Time frame: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h, 4 h, 6h, 8h, 10h, 12 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After First Dose of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of the first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FEV1 AUC 0-3h was calculated from 0-3hours post-dose using the trapezoidal rule, divided by the observation time (3 h) to report in litres.

Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose of the first period (study baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to the first dose of treatment period

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment

Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to the last dose of treatment after six weeks of treatment.

Peak FEV1 (0-3h) Response

Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of first treatment period. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after the first dose of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate.

Time frame: Study baseline and first day of dosing

Peak FEV1 (0-3h) Response

Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of first treatment period. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after the last dose after six weeks of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate.

Time frame: Study baseline and 6 weeks

Trough FEV1 Response

Response was defined as change from baseline. Study baseline trough FEV1 was defined as the mean of the available pre-dose trough FEV1 values prior to first dose of first treatment period. Trough values were the mean of values obtained 23 hours and 23h 50min post the last dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate.

Time frame: Study baseline and 6 weeks

Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to first dose in first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of the first treatment period (study baseline) and -30 min (zero time), 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12h relative to last dose after six weeks of treatment.

FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to first dose of first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Time frame: 1 h and 10 min prior to dose on the first day of the first treatment period (study baseline) and 12 h, 22 h, 23 h, and 23 h 50 min relative to last dose after six weeks of treatment

FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to first dose in first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h, 4 h, 6h, 8h, 10h, 12 h, 22 h, 23 h, and 23 h 50 min relative to last dose after six weeks of treatment.

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose in the first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of the treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h relative to first dose of treatment

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response

Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h relative to last dose after six weeks of treatment.

Peak FVC (0-3h) Response

Response was defined as change from baseline. Study baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose in first treatment period. Peak FVC (0-3h) was obtained within 0 - 3 hours after the last dose of study drug after 6 weeks of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate.

Time frame: Study baseline and 6 weeks

Trough FVC Response

Response was defined as change from baseline. Study baseline trough FVC was defined as the mean of the available pre-dose trough FVC values prior to first dose in first treatment period. Trough values were mean of the values obtained 23 h and 23 h 50 min after the last dose of study drug after six weeks of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate.

Time frame: Study baseline and 6 weeks

Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG

Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations).

Time frame: 6 weeks