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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Olodaterol (BI1744CL); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • 1222.4.103 UBC - Respiratory Medicine
  • Ontario
    • Hamilton, Ontario, Canada
      • 1222.4.104 Department of Medicine, Health Sciences Centre
  • Quebec
    • Sainte-Foy, Quebec, Canada
      • 1222.4.101 2725 Chemin Ste Foy
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • 1222.4.102

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Diagnosis of intermittent asthma according to Global Initiative for Asthma criteria
2. 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
3. Forced Expiratory Volume in 1second greater than or equal to 80% predicted normal (Visit 1).
4. 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).
5. Be able to perform technically acceptable pulmonary function tests
6. Be able to inhale medication in a competent manner from the Respimat® inhaler
7. 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

1. Patients with a significant disease other than asthma
2. Patients with seasonal asthma or allergies whose participation in the trial will occur during the season for which they are allergic.
3. 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
4. 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.
5. Patients who have undergone thoracotomy with pulmonary resection
6. 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.
7. 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).
8. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1).
9. Pregnant or nursing women, or women of childbearing potential not using a highly effective method of birth control.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: June 25, 2009
• First Submitted That Met QC Criteria: June 25, 2009
• First Posted (Estimate): June 26, 2009

Study Record Updates

• Last Update Posted (Estimate): July 1, 2014
• Last Update Submitted That Met QC Criteria: May 29, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Olodaterol
• Other Study ID Numbers: 1222.4