Characterisation of 24-hour FEV1-time Profiles of Inhaled BI 1744 CL and Inhaled Foradil in Patients With Chronic Obstructive Pulmonary Disease

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

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 Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: BI 1744 (Olodaterol) Medium Dose; Drug: BI 1744 (Olodaterol) Low Dose; Drug: Placebo; Drug: Foradil

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Jasper, Alabama, United States
      • 1222.25.25009 Boehringer Ingelheim Investigational Site
  • Florida
    • Clearwater, Florida, United States
      • 1222.25.25002 Boehringer Ingelheim Investigational Site
    • Deland, Florida, United States
      • 1222.25.25003 Boehringer Ingelheim Investigational Site
    • Winter Park, Florida, United States
      • 1222.25.25007 Boehringer Ingelheim Investigational Site
  • Georgia
    • Austell, Georgia, United States
      • 1222.25.25010 Boehringer Ingelheim Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States
      • 1222.25.25008 Boehringer Ingelheim Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • 1222.25.25012 Boehringer Ingelheim Investigational Site
    • Raleigh, North Carolina, United States
      • 1222.25.25004 Boehringer Ingelheim Investigational Site
  • Ohio
    • Columbus, Ohio, United States
      • 1222.25.25011 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Seneca, South Carolina, United States
      • 1222.25.25014 Boehringer Ingelheim Investigational Site
  • Tennessee
    • Knoxville, Tennessee, United States
      • 1222.25.25006 Boehringer Ingelheim Investigational Site
  • Texas
    • Houston, Texas, United States
      • 1222.25.25005 Boehringer Ingelheim Investigational Site
  • Virginia
    • Richmond, Virginia, United States
      • 1222.25.25013 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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 use
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI1744 (Olodaterol); Medium Dose once Daily	Drug: BI 1744 (Olodaterol) Medium Dose; BI1744 Respimat medium dose once daily and placebo Foradil
Experimental: BI 1744 (Olodaterol); Low Dose once Daily	Drug: BI 1744 (Olodaterol) Low Dose; BI1744 Respimat low dose once daily and placebo Foradil
Placebo Comparator: Placebo; Placebo once Daily	Drug: Placebo; Placebo Respimat once daily and placebo Foradil
Active Comparator: Foradil; 12 mcg twice daily	Drug: Foradil; 12 mcg twice daily and placebo Respimat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. 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 treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min 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, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. 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 treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.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 h and 10 min prior to am dose on the first day of the treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 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 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 randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. 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 (baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to am dose after six weeks of treatment
Peak FEV1 (0-3h) Response	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak values were obtained within 0 - 3 hours after the last am dose after six weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.	Baseline and 6 weeks
Trough FEV1 Response	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.	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 at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. 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 am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am 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 at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. 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 am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am 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 at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.	1 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.
Peak FVC (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 at the randomisation visit. Peak FVC 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 center, treatment and period as fixed effects and patient within center as random.	Baseline and 6 weeks
Trough FVC Response	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.	Baseline and 6 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Feldman GJ, Bernstein JA, Hamilton A, Nivens MC, Korducki L, LaForce C. The 24-h FEV1 time profile of olodaterol once daily via Respimat(R) and formoterol twice daily via Aerolizer(R) in patients with GOLD 2-4 COPD: results from two 6-week crossover studies. Springerplus. 2014 Aug 9;3:419. doi: 10.1186/2193-1801-3-419. eCollection 2014.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: July 2, 2009
• First Submitted That Met QC Criteria: July 2, 2009
• First Posted (Estimate): July 3, 2009

Study Record Updates

• Last Update Posted (Estimate): February 5, 2016
• Last Update Submitted That Met QC Criteria: January 11, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Olodaterol; Formoterol Fumarate
• Other Study ID Numbers: 1222.25