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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

Randomised, Double-blind, Double-dummy, Placebo-controlled, 4-way Cross-over Study to Characterise the 24-hour Forced, Expiratory Volume After 1 Second (FEV1) Time Profiles of BI 1744 CL 5µg and 10µg (Oral Inhalation, Delivered by the Respimat® Inhaler) and Tiotropium Bromide 18µg (Oral Inhalation, Delivered by the HandiHaler®) After 6 Weeks of Treatment in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01040689
• Other study ID #: 1222.39
• Secondary ID: 2009-014417-27
• Status: Completed
• Phase: Phase 3
• First received: December 29, 2009
• Last updated: May 28, 2014
• Start date: January 2010

Study information

• Verified date: May 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal and Health ProductsDenmark: Danish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of Pharmacy
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Olodaterol (BI1744) Low
Low dose inhaled orally once daily from Respimat inhaler
• Placebo (for olodaterol BI1744)
Placebo (olodaterol low and high dose)delivered by Respimat
• Placebo (for Tiotropium)
Placebo (Tiotropium 18 mcg) delivered by HandiHaler
• Olodaterol (BI1744) High
High dose inhaled orally once daily from Respimat inhaler
• Tiotropium 18 mcg
18mcg inhaled once daily from Handihaler

Locations

Country	Name	City	State
Belgium	1222.39.32003 Boehringer Ingelheim Investigational Site	Genk
Belgium	1222.39.32001 Boehringer Ingelheim Investigational Site	Gent
Belgium	1222.39.32002 Boehringer Ingelheim Investigational Site	Hasselt
Denmark	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
Germany	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
Hungary	1222.39.36006 Boehringer Ingelheim Investigational Site	Deszk
Hungary	1222.39.36004 Boehringer Ingelheim Investigational Site	Farkasgyepü
Hungary	1222.39.36005 Boehringer Ingelheim Investigational Site	Pecs
Hungary	1222.39.36003 Boehringer Ingelheim Investigational Site	Szarvas
Hungary	1222.39.36001 Boehringer Ingelheim Investigational Site	Szeged
Hungary	1222.39.36002 Boehringer Ingelheim Investigational Site	Törökbalint

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Belgium,  Denmark,  Germany,  Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	No
Primary	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.	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	No
Secondary	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.	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	No
Secondary	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.	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	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) 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 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.	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.	No
Secondary	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.	Study baseline and first day of dosing	No
Secondary	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.	Study baseline and 6 weeks	No
Secondary	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.	Study baseline and 6 weeks	No
Secondary	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.	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.	No
Secondary	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.	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	No
Secondary	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.	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.	No
Secondary	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.	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	No
Secondary	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.	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.	No
Secondary	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.	Study baseline and 6 weeks	No
Secondary	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.	Study baseline and 6 weeks	No
Secondary	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).	6 weeks	No

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