A Randomized, Double-Blind, 4-way Crossover Study to Evaluate the Efficacy of of 24 Hour Spirometry Profiles of Inhaled BI 1744 CL and Inhaled Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01040728
First received: December 29, 2009
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

The study is intended to characterize the lung function profile of BI1744 in Chronic Obstructive Pulmonary Disease (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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Olodaterol (BI1744) Low
Drug: Olodaterol (BI1744) High
Drug: Tiotropium 18 mcg
Drug: Placebo (for Olodaterol (BI1744)l)
Drug: Placebo (for Tiotropium)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Randomised, Double-blind, Double-dummy, Placebo-controlled, 4-way Cross-over Study to Characterise the 24-hour 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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment [ Time Frame: 1 hour (h) and 10 minutes (min) prior to the 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 ] [ Designated as safety issue: No ]
    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 first 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.

  • FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment [ Time Frame: 1 h and 10 min prior to the 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 ] [ Designated as safety issue: No ]
    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 first 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.


Secondary Outcome Measures:
  • Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment [ 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 ] [ Designated as safety issue: No ]
    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 at the first randomized treatment visit for the first 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.

  • Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After First Dose of Treatment [ Time Frame: 1 hour (h) prior and 10 minutes (min) prior to the am 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 the first dose of treatment period ] [ Designated as safety issue: No ]
    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 treatment at the first treatment visit for the first 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.

  • 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 the am 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 the first dose of treatment after six weeks of treatment ] [ Designated as safety issue: No ]
    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 treatment for the first 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.

  • Peak FEV1 (0-3h) Response [ Time Frame: Study baseline and first day of dosing ] [ Designated as safety issue: No ]
    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 treatment for the first 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.

  • Peak FEV1 (0-3h) Response [ Time Frame: Study baseline and 6 weeks ] [ Designated as safety issue: No ]
    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 treatment for the first 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.

  • Trough FEV1 Response [ Time Frame: Study baseline and 6 weeks ] [ Designated as safety issue: No ]
    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 treatment for the first period. Trough values were the mean of values obtained 23h 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.

  • Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response [ Time Frame: 1 hour (h) and 10 minutes (min) prior to the am 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. ] [ Designated as safety issue: No ]
    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 treatment for the first 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.

  • FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response [ Time Frame: 1 h and 10 min prior to the 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 last dose after six weeks of treatment ] [ Designated as safety issue: No ]
    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 treatment for the first 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.

  • FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response [ 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 last dose after six weeks of treatment ] [ Designated as safety issue: No ]
    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 treatment for the first 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.

  • FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response [ Time Frame: 1 hour (h) and 10 minutes (min) prior to the am 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 first dose of treatment ] [ Designated as safety issue: No ]
    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 of treatment for the first 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.

  • FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response [ Time Frame: 1 hour (h) and 10 minutes (min) prior to the am 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 of treatment after six weeks of treatment ] [ Designated as safety issue: No ]
    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 of treatment for the first 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.

  • Peak FVC (0-3h) Response [ Time Frame: Study baseline and 6 weeks ] [ Designated as safety issue: No ]
    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 of treatment for the first period. Peak FVC (0-3h) was obtained within 0 - 3 hours after the last am 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.

  • Trough FVC Response [ Time Frame: Study baseline and 6 weeks ] [ Designated as safety issue: No ]
    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 of treatment for the first period. Trough values were the mean of 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.

  • Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    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).


Enrollment: 122
Study Start Date: January 2010
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olodaterol (BI1744) Low
Low dose inhaled orally once daily from Respimat inhaler
Drug: Olodaterol (BI1744) Low
Low dose inhaled orally once daily from Respimat inhaler
Experimental: Olodaterol (BI1744) High
High dose inhaled orally once daily from Respimat inhaler
Drug: Olodaterol (BI1744) High
High dose inhaled orally once daily from Respimat inhaler
Active Comparator: Tiotropium 18 mcg
18 mcg inhaled once daily from HandiHaler
Drug: Tiotropium 18 mcg
18 mcg inhaled once daily from HandiHaler
Placebo Comparator: Placebo
Olodaterol placebo and/or Tiotropium placebo inhaled once daily
Drug: Placebo (for Olodaterol (BI1744)l)
Placebo (olodaterol low and high dose) delivered by Respimat
Drug: Placebo (for Tiotropium)
Placebo (Tiotropium 18 mcg) delivered by HandiHaler

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01040728

Locations
United States, Alabama
1222.40.11003 Boehringer Ingelheim Investigational Site
Jasper, Alabama, United States
United States, Florida
1222.40.11001 Boehringer Ingelheim Investigational Site
Clearwater, Florida, United States
1222.40.11002 Boehringer Ingelheim Investigational Site
Tampa, Florida, United States
Germany
1222.40.49401 Boehringer Ingelheim Investigational Site
Berlin, Germany
1222.40.49403 Boehringer Ingelheim Investigational Site
Berlin, Germany
1222.40.49402 Boehringer Ingelheim Investigational Site
Hannover, Germany
Netherlands
1222.40.31003 Boehringer Ingelheim Investigational Site
Breda, Netherlands
1222.40.31002 Boehringer Ingelheim Investigational Site
Eindhoven, Netherlands
1222.40.31001 Boehringer Ingelheim Investigational Site
Heerlen, Netherlands
Norway
1222.40.47003 Boehringer Ingelheim Investigational Site
Arendal, Norway
1222.40.47002 Boehringer Ingelheim Investigational Site
Drammen, Norway
1222.40.47001 Boehringer Ingelheim Investigational Site
Trondheim, Norway
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01040728     History of Changes
Other Study ID Numbers: 1222.40, 2009-014418-86
Study First Received: December 29, 2009
Results First Received: March 28, 2014
Last Updated: May 28, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Central Committee Research Involving Human Subjects
Norway: Norwegian Medicines Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Tiotropium
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014