Single Dose Ranging Study of BI 1744 CL (Olodaterol) in Chronic Obstructive Pulmonary Disease

Single Dose Preliminary Dose-ranging and Safety in Patients With COPD

Primary objective: To investigate bronchodilator effect and safety of single doses of BI 1744 CL inhaled via Respimat inhaler, Secondary objective: to characterize pharmacokinetics of BI 1744 CL. Olodaterol dose 40 mcg was investigated only in the open-label extension part for additional PK assessments which are not defined as primary or secondary endpoints.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: single dose of 2 mcg; Drug: single dose of 5 mcg; Drug: single dose of 10 mcg; Drug: single dose of 20 mcg; Drug: single dose of 40 mcg; Drug: single dose of placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Heerlen, Netherlands
    • 1222.3.1 Atrium medisch centrum

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:

1. Diagnosis of chronic obstructive pulmonary disease
2. Smoking history of more than 10-pack years

Exclusion criteria:

1. History of asthma, allergic rhinitis, myocardial infarction or unstable of life-threatening cardiac arrhythmias
2. Marked baseline prolongation of QT/QTc interval

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: olodaterol 2 mcg; solution for inhalation	Drug: single dose of 2 mcg; solution for inhalation
Experimental: olodaterol 5 mcg; solution for inhalation	Drug: single dose of 5 mcg; solution for inhalation
Experimental: olodaterol 10 mcg; solution for inhalation	Drug: single dose of 10 mcg; solution for inhalation
Experimental: olodaterol 20 mcg; solution for inhalation	Drug: single dose of 20 mcg; solution for inhalation
Experimental: olodaterol 40 mcg; solution for inhalation	Drug: single dose of 40 mcg; solution for inhalation
Placebo Comparator: placebo; solution for inhalation	Drug: single dose of placebo; solution for inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in One Second (FEV1) at 24 Hours After a Single-dose of Study Treatment	Forced expiratory volume in one second (FEV1) at 24 hours after a single-dose of study treatment. Means are adjusted with test-day baseline, patient, treatment, and period as fixed effects. Test-day baseline value was defined as the value at 10 minutes before inhalation of study medication.	24 hours post-dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 AUC 0 - 3 Hours	The FEV1 AUC was calculated as the area under the curve above zero as the horizontal axis from zero time to 3 hours, using the trapezoidal rule divided by 3 hours to give the results in litres. The test-day baseline (defined as the pulmonary function test (PFT) at 10 minutes before inhalation of study medication) was assigned to time zero.	-10 minutes (min), 30min, 1 hour (h), 2h and 3h post-dosing
FEV1 AUC 0 - 12 Hours	The FEV1 AUC was calculated as the area under the curve above zero as the horizontal axis from zero time to 12 hours, using the trapezoidal rule divided by 12 hours to give the results in litres. The test-day baseline (defined as the pulmonary function test (PFT) at 10 minutes before inhalation of study medication) was assigned to time zero.	-10 minutes (min), 30min, 1 hour (h), 2h, 3h, 4h, 6h, 8h, 10h and 12h post-dosing
FEV1 AUC 0 - 24 Hours	The FEV1 AUC was calculated as the area under the curve above zero as the horizontal axis from zero time to 24 hours, using the trapezoidal rule divided by 24 hours to give the results in litres. The test-day baseline (defined as the pulmonary function test (PFT) at 10 minutes before inhalation of study medication) was assigned to time zero.	-10 minutes (min), 30min, 1 hour (h), 2h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 22h, 23h and 24h post-dosing
FEV1 AUC 12 - 24 Hours	The FEV1 AUC was calculated as the area under the curve above zero as the horizontal axis from 12 hours to 24 hours, using the trapezoidal rule divided by 12 hours to give the results in litres. The test-day baseline (defined as the pulmonary function test (PFT) at 10 minutes before inhalation of study medication) was assigned to time zero.	12h, 14h, 22h, 23h and 24h post-dosing
Peak FEV1 From 0 to 3 Hours	Peak FEV1 was defined as the maximum values of FEV1 from 0 to 3 hours.	0 to 3 hours post-dosing
Peak Forced Vital Capacity (FVC) From 0 to 3 Hours	Peak FVC was defined as the maximum values of FVC from 0 to 3 hours.	0 to 3 hours post-dosing
Time to Peak Bronchodilator Response	A bronchodilator response was considered to have been achieved if an FEV1 measurement of at least 12% greater than the test-day baseline value was recorded at any time during the first 3 hours of observation after dosing.	0 to 3 hours post-dosing
Time to Onset of Response	Onset of the bronchodilator response after a single dose of study treatment was defined as the linear interpolation of the time of the first bronchodilator response and the time of the observation just prior to the first bronchodilator response (even if that is the baseline observation). If none of the FEV1 values in the first 3 hours after dosing exceeded 12% of the pre-dose value, then the onset was set to 3 hours plus 1 minute.	0 to 3 hours post-dosing
Number of Patients Requiring Rescue Medication on a Test-day	Number of Patients Requiring Rescue Medication on a Test-day. Salbutamol inhalation aerosol MDI (Ventolin®, 100 μg/actuation) was provided for use as rescue medication. Administration of rescue medication can occur at any point during the pulmonary function testing as deemed necessary by the patient or the investigator.	Visits 1,2,4,5,6
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 (cardiac disorders and investigations).	2 weeks
Laboratory Testing: Average Change From Baseline of Potassium and Calcium	Laboratory testing: Average change from baseline of potassium and calcium measured on test-days	Baseline and Visit 6

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): November 1, 2006
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: March 8, 2013
• First Submitted That Met QC Criteria: March 8, 2013
• First Posted (Estimate): March 12, 2013

Study Record Updates

• Last Update Posted (Estimate): June 30, 2014
• Last Update Submitted That Met QC Criteria: May 27, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 1222.3