Efficacy (Bronchoprotection) and Safety of Orally Inhaled BI 1744 CL in Patients With Intermittent Asthma

Study Overview
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Brief Summary
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The primary objective of this study is to assess the efficacy (bronchoprotection) and safety of single doses of BI 1744 CL inhalation solution (2, 5, 10 and 20 mcg) delivered via the Respimat® inhaler, in patients with intermittent asthma.

Official Title
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Randomised, Double-Blind, Placebo-Controlled, 5-Way Cross-Over Study to Assess the Efficacy (Bronchoprotection) and Safety of a Single Dose of Orally Inhaled BI 1744 CL (2, 5, 10 and 20ug) in Patients With Intermittent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Placebo
* Drug: Olodaterol (BI1744CL)
* Drug: Olodaterol (BI1744CL)
* Drug: Olodaterol (BI1744CL)
* Drug: Olodaterol (BI1744CL)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Diagnosis of intermittent asthma according to Global Initiative for Asthma criteria Non-smokers or ex-smokers who have not smoked for at least 1 year and have a smoking history of less than 5 pack-years Forced Expiratory Volume in 1second greater than or equal to 80% predicted normal (Visit 1). Bronchial hyperresponsiveness to inhaled methacholine with a provocative concentration of a methacholine causing a 20% fall in Forced Expiratory Volume in one second less than or equal to 8 mg/mL (Visit 1). Be able to perform technically acceptable pulmonary function tests Be able to inhale medication in a competent manner from the Respimat® inhaler Must sign and date an informed consent consistent with International Conference on Harmonisation-Good Clinical Practice guidelines prior to participation in the trial, which includes medication washout and restrictions. Exclusion criteria Patients with a significant disease other than asthma Patients with seasonal asthma or allergies whose participation in the trial will occur during the season for which they are allergic. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with a serum glutamic oxaloacetic transaminase > 80 IU/L, serum glutamic pyruvic transaminase > 80 IU/L, bilirubin >2.0 mg/dL or creatinine > 2.0 mg/dL will be excluded regardless of clinical condition Patients with any of the following conditions: a diagnosis of hyperthyrosis or paroxysmal tachycardia (>100 beats per minute), a marked baseline prolongation of QT/QTc interval, a history of additional risk factors for Torsade de Pointes, a history of myocardial infarction, a diagnosis of clinically relevant cardiac arrhythmia, a history of cor pulmonale, known active tuberculosis, a malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years (patients with treated basal cell carcinoma are allowed), a history of life-threatening pulmonary obstruction, a history of cystic fibrosis, clinically evident bronchiectasis, or a history of significant alcohol or drug abuse. Patients who have undergone thoracotomy with pulmonary resection Patients who are being treated with any of the following concomitant medications: medications that prolong the QT/QTc interval, oral beta-adrenergics, beta-blockers or monoamine oxidase inhibitors or tricyclic antidepressants. Patients who have been treated with any respiratory medications (excluding short-acting beta-agonists) for control of their asthma symptoms within 3 months of the Screening Visit (Visit 1). Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1). Pregnant or nursing women, or women of childbearing potential not using a highly effective method of birth control.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olodaterol (BI1744) Low<br>Single dosing of low dose Olodaterol inhaled orally from Respimat Device | Drug: Olodaterol (BI1744CL)<br>* Olodaterol comparison of low, medium low, medium high and high doses<br>|
| Experimental: Olodaterol (BI1744) Medium Low<br>Single dosing of medium low dose Olodaterol inhaled orally from Respimat Device | Drug: Olodaterol (BI1744CL)<br>* Olodaterol comparison of low, medium low, medium high and high doses<br>|
| Experimental: Olodaterol (BI1744) Medium High<br>Single dosing of medium high dose Olodaterol inhaled orally from Respimat Device | Drug: Olodaterol (BI1744CL)<br>* Olodaterol comparison of low, medium low, medium high and high doses<br>|
| Experimental: Olodaterol (BI 1744) High<br>Single dosing of high dose Olodaterol inhaled orally from Respimat Device | Drug: Olodaterol (BI1744CL)<br>* Olodaterol comparison of low, medium low, medium high and high doses<br>|
| Placebo Comparator: Placebo<br>Single dosing of Olodaterol placebo inhaled orally from Respimat Device | Drug: Placebo<br>* Placebo device for comparison<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 24 Hours | Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 24 hours | 24 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 30 Minutes | Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 30 minutes | 30 minutes post dose | 
| Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 4 Hours | Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 4 hours | 4 hours post dose | 
| Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 8 Hours | Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 8 hours | 8 hours post dose | 
| Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 32 Hours | Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 32 hours | 32 hours post dose | 
| 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). | 5 days | 
| 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 to Visit 6 |