Dose Finding Study on BI54903 (Inhaled Corticosteroid) Administered Twice Daily Via Respimat® Inhaler in Asthmatic Patients Inadequately Controlled on Short-acting-beta-agonist (SABA) Therapy

A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Study to Assess and Compare Efficacy and Safety of an 8-week Treatment With BI 54903 at Doses of 22.7, 45.5 and 90.9 Doses b.i.d. Administered Via Respimat® Inhaler and Fluticasone Propionate HFA MDI 88 mcg b.i.d. in Patients With Asthma Inadequately Controlled on SABA Therapy

The aim of the study is to assess and compare efficacy and safety of BI 54903 at 3 doses twice daily (b.i.d.) and fluticasone propionate hydrofluoroalkane metered dose inhaler (HFA MDI) at a dose of 88 mcg b.i.d and placebo b.i.d. over an 8-week treatment period in asthmatic patients aged 12 to 65 years inadequately controlled on short-acting-beta-agonist (SABA) prn therapy only as demonstrated by a decrease in forced expiratory volume in one second (FEV1) range10 to 25% and an asthma control questionnaire (ACQ-6) equal or greater than 1.5 at time of randomization

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone propionate; Drug: Placebo; Drug: BI 54903

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Fountain Valley, California, United States
      • 1248.5.01047 Boehringer Ingelheim Investigational Site
    • Huntington Beach, California, United States
      • 1248.5.01041 Boehringer Ingelheim Investigational Site
    • Long Beach, California, United States
      • 1248.5.01038 Boehringer Ingelheim Investigational Site
    • Mission Viejo, California, United States
      • 1248.5.01004 Boehringer Ingelheim Investigational Site
    • Palmdale, California, United States
      • 1248.5.01028 Boehringer Ingelheim Investigational Site
    • Rancho Mirage, California, United States
      • 1248.5.01014 Boehringer Ingelheim Investigational Site
    • Stockton, California, United States
      • 1248.5.01044 Boehringer Ingelheim Investigational Site
  • Colorado
    • Centennial, Colorado, United States
      • 1248.5.01015 Boehringer Ingelheim Investigational Site
  • Florida
    • Miami, Florida, United States
      • 1248.5.01022 Boehringer Ingelheim Investigational Site
    • Sarasota, Florida, United States
      • 1248.5.01042 Boehringer Ingelheim Investigational Site
  • Georgia
    • Columbus, Georgia, United States
      • 1248.5.01051 Boehringer Ingelheim Investigational Site
    • Savannah, Georgia, United States
      • 1248.5.01052 Boehringer Ingelheim Investigational Site
  • Idaho
    • Eagle, Idaho, United States
      • 1248.5.01011 Boehringer Ingelheim Investigational Site
  • Illinois
    • Oak Lawn, Illinois, United States
      • 1248.5.01055 Boehringer Ingelheim Investigational Site
  • Maryland
    • Baltimore, Maryland, United States
      • 1248.5.01019 Boehringer Ingelheim Investigational Site
  • Massachusetts
    • North Dartmouth, Massachusetts, United States
      • 1248.5.01039 Boehringer Ingelheim Investigational Site
  • Michigan
    • Ypsilanti, Michigan, United States
      • 1248.5.01037 Boehringer Ingelheim Investigational Site
  • Missouri
    • Rolla, Missouri, United States
      • 1248.5.01056 Boehringer Ingelheim Investigational Site
    • Warrensburg, Missouri, United States
      • 1248.5.01036 Boehringer Ingelheim Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States
      • 1248.5.01020 Boehringer Ingelheim Investigational Site
  • New Jersey
    • Berlin, New Jersey, United States
      • 1248.5.01049 Boehringer Ingelheim Investigational Site
    • Trenton, New Jersey, United States
      • 1248.5.01054 Boehringer Ingelheim Investigational Site
    • Verona, New Jersey, United States
      • 1248.5.01010 Boehringer Ingelheim Investigational Site
  • New York
    • Rochester, New York, United States
      • 1248.5.01006 Boehringer Ingelheim Investigational Site
  • North Carolina
    • High Point, North Carolina, United States
      • 1248.5.01031 Boehringer Ingelheim Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States
      • 1248.5.01045 Boehringer Ingelheim Investigational Site
  • Oregon
    • Gresham, Oregon, United States
      • 1248.5.01005 Boehringer Ingelheim Investigational Site
    • Portland, Oregon, United States
      • 1248.5.01021 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • 1248.5.01013 Boehringer Ingelheim Investigational Site
    • Pittsburgh, Pennsylvania, United States
      • 1248.5.01040 Boehringer Ingelheim Investigational Site
    • Upland, Pennsylvania, United States
      • 1248.5.01012 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States
      • 1248.5.01048 Boehringer Ingelheim Investigational Site
  • Texas
    • Austin, Texas, United States
      • 1248.5.01050 Boehringer Ingelheim Investigational Site
    • Live Oak, Texas, United States
      • 1248.5.01002 Boehringer Ingelheim Investigational Site
    • San Antonio, Texas, United States
      • 1248.5.01032 Boehringer Ingelheim Investigational Site
    • San Antonio, Texas, United States
      • 1248.5.01046 Boehringer Ingelheim Investigational Site
    • Waco, Texas, United States
      • 1248.5.01001 Boehringer Ingelheim Investigational Site
    • Waco, Texas, United States
      • 1248.5.01007 Boehringer Ingelheim Investigational Site
  • Utah
    • Murray, Utah, United States
      • 1248.5.01025 Boehringer Ingelheim Investigational Site
  • Virginia
    • Alexandria, Virginia, United States
      • 1248.5.01053 Boehringer Ingelheim Investigational Site
  • Washington
    • Tacoma, Washington, United States
      • 1248.5.01030 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Male and female patients aged at least 12 to 65 years
2. All patients must have a history of asthma diagnosed by a physician for at least three months at the time of enrolment into the trial according to the 2009 Global Initiative for Asthma (GINA) Guidelines. The initial diagnosis of asthma must have been made before the age of 40 years 4 All patients must be on a maintenance treatment with either low-dose inhaled corticosteroid (ICS) plus long-acting-beta -agonist (LABA) or medium-dose ICS without LABA, stable for at least six weeks prior to Visit 1

5 All patients must have a pre-bronchodilator FEV1 of not less than 60 to 90% of predicted normal and an asthma control questionnaire (ACQ-6) mean score of less than 1.5 at the pre-screening Visit 1 6 All patients must have an improvement in forced expiratory volume in one second (FEV1) not less than 12 % above baseline and an absolute change of at least 200 mL within 15-30 min after administration of 400 mcg salbutamol/albuterol hydrofluoroalkane metered dose inhaler (HFA MDI) 7 Patients must be never-smokers or ex-smokers with a smoking history of less than 10 pack-years and smoking cessation at least one year prior to screening 9 Patients must be able to use Respimat® inhaler and metered dose inhaler (MDI) correctly 10 Patients must be able to perform all trial-related procedures including technically acceptable pulmonary function tests and electronic peak expiratory flow (PEF) measurements, and must be able to maintain records during the study period as required in the protocol

Exclusion criteria:

1. Patients with significant pulmonary disease other than asthma or other significant medical conditions (as determined by medical history, examination and clinical investigations at screening)
2. Patients with a clinically relevant, abnormal screening haematology and/or blood chemistry finding
3. Patients with a history of upper or lower respiratory tract infection (URTI/LRTI) in the past four weeks prior to the pre-screening Visit 1, and during pre-screening and run-in periods
4. Patients with any exacerbation of their underlying asthma during the eight weeks prior to the pre-screening Visit 1
5. Patients with active allergic rhinitis requiring treatment with systemic corticosteroids
6. Any of the following criteria are met during the pre-screening / run-in period (Visits 1 - 6):in clinic pre-bronchodilator forced expiratory volume in one second (FEV1 %) predicted less than 40%; more than 12 puffs rescue salbutamol/albuterol HFA MDI per day for > 2 consecutive days;exacerbation of asthma
7. Patients with a history of pneumonectomy or who are planning to undergo thoracotomy for any reason
8. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the six weeks prior to the first screening visit 1
9. Patients with two or more hospitalizations for asthma within the previous 12 months
10. Patients with a recent history of myocardial infarction during the last twelve months or known coronary heart disease that requires treatment
11. Patients with a history of hospitalisation due to heart failure in the past twelve months
12. Patients with myocarditis or any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year
13. Patients with significant alcohol or drug abuse in the opinion of the investigator within the past two years
14. Patients with rheumatoid arthritis or other systemic diseases that require immune system modulating treatment
15. Patients suffering from narrow angle glaucoma with a history of glaucoma, increased intraocular pressure, and/or cataracts
16. Pregnant or nursing women
17. Women of childbearing potential not using a highly effective method of birth control
18. Patients who have been treated with anti-Immunoglobin-E-antibodies (e.g. omalizumab, Xolair®) or other immune system modulating antibodies such as tumor necrosis factor-alpha blockers within six months prior to Visit 1
19. Patients who have been treated with the following drugs during the past four weeks prior to Visit 1 or are foreseen to need this during the study:Non-selective beta-blockers (topical cardio-selective beta-blocker eye medications for non-narrow angle glaucoma are allowed; Oral or other systemic corticosteroids; Oral beta-agonists; Changes in allergen desensitisation therapy in last 6 months; Immune system modulating agents such as methotrexate or cyclosporine; Inhibitors of cytochrome P450 3A4 such as antifungals (e.g. ketoconazole, itraconazole), antibiotics (e.g. erythromycin) or antiretroviral drugs; Patients who have been treated with leukotriene modifiers, chromones or theophylline within two weeks prior to Visit 1; Patients who have been treated with tiotropium within 3 weeks prior to Visit 1

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 54903 - low dose; BI 54903 low dose 2 puffs twice daily (b.i.d.) via Respimat inhaler plus hydrofluoralkane (HFA) metered dose inhaler (MDI) matching placebo 2 puffs b.i.d.	Drug: BI 54903; BI 54903
Experimental: BI 54903 - medium dose; BI 54903 medium dose 2 puffs b.i.d. via Respimat inhaler plus HFA MDI matching placebo 2 puffs b.i.d.	Drug: BI 54903; BI 54903
Experimental: BI 54903 - high dose; BI 54903 high dose 2 puffs b.i.d. via Respimat inhaler plus HFA MDI matching placebo 2 puffs b.i.d.	Drug: BI 54903; BI 54903
Active Comparator: Fluticasone propionate; Fluticasone propionate 2 puffs twice b.i.d via HFA MDI plus placebo BI 54903 via Respimat inhaler 2 puffs b.i.d.	Drug: Fluticasone propionate; Fluticasone propionate
Placebo Comparator: Placebo; Placebo Respimat inhaler 2 puffs b.i.d. and placebo HFA MDI, 2 puffs b.i.d.	Drug: Placebo; Placebo matching fluticasone propionate HFA MDI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From the Randomisation Baseline to the End of the 8-week Treatment Period in Trough (Morning Pre-dose and Pre-rescue Bronchodilator ) Forced Expiratory Volume in One Second (FEV1)	Mean change from the randomisation baseline to the end of the 8-week treatment period in trough (morning pre-dose and pre-rescue bronchodilator ) forced expiratory volume in one second (FEV1).	At baseline and week 8.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Changes From Randomisation Baseline in Trough (Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in One Second (FEV1) After 2 and 4-week Treatment Periods	Mean changes from randomisation baseline in trough (pre-dose and pre-rescue bronchodilator) forced expiratory volume in one second (FEV1) after 2 and 4-week treatment periods.	At baseline and at week 2 and 4.
Mean Rescue Medication Use (Daytime and Night-time) as Assessed Via Asthma Monitor (AM2+) in the Morning and Evening, of the Last Week of the 8-week Treatment Period	Mean rescue medication use (daytime and night-time) as assessed via asthma monitor (AM2+) in the morning and evening, of the last week of the 8-week treatment period.	At week 8.
Mean Change From Randomisation Baseline in Asthma Control Questionnaire (ACQ-6) Scores at Subsequent Study Visits	The Asthma Control Questionnaire (ACQ) consists of 6 patient self-evaluated questions with each question in 7-point scale. The items are equally weighted and the ACQ score is the mean of 6 items and ranges between 0 (well controlled) and 6 (extremely poorly controlled). Mean scores of less than or equal to 0.75 indicate well-controlled asthma, scores between 0.76 and less than 1.5 indicate partly controlled asthma, and a score greater than or equal to 1.5 indicates uncontrolled asthma.	At baseline and at week 2, 4 and 8.
Mean Change From Randomisation Baseline in Asthma Quality of Life Questionnaire (AQLQ(S)+12) Scores at Subsequent Study Visits	AQLQ(S)+12 are well established and validated questionnaires to measure control of asthma symptoms and quality of life, which is a patient-reported self-administered outcome questionnaire containing 32 items. Each item is scored on a 7-point scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire are averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life.	At baseline and at week 2, 4 and 8.
Time to Withdrawal Due to First Asthma Exacerbation	Time to withdrawal due to first asthma exacerbation.	At week 8.
Mean Changes From Randomisation Baseline in Trough (Pre-dose and Pre-rescue Bronchodilator) Forced Vital Capacity (FVC) After 2, 4 and 8-week Treatment Periods	Mean changes from randomisation baseline in trough (pre-dose and pre-rescue bronchodilator) forced vital capacity (FVC) after 2, 4 and 8-week treatment periods.	At baseline and week 2, 4, 8.
Mean Changes From Randomisation Baseline in Trough (Morning Pre-dose and Prerescue Bronchodilator) FEF25-75 After 2, 4 and 8-week Treatment Periods	Mean change from randomization baseline in through (morning pre-dose and pre-rescue bronchodilator) Forced expiratory flow between 25% and 75% of vital capacity (FEF 25-75) after 2, 4 and 8-week treatment periods.	At baseline and at week 2, 4 and 8.
Mean Pre-dose (and Pre-rescue) Peak Expiratory Flow (PEF) as Assessed Via Asthma Monitor (AM2+) in the Morning and Evening, of the Last Week of the 8-week Treatment Period	Mean pre-dose (and pre-rescue) peak expiratory flow (PEF) as assessed via asthma monitor (AM2+) in the morning and evening of the last week of the 8-week treatment period.	At week 8.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2011
• Primary Completion (Actual): December 23, 2011
• Study Completion (Actual): December 23, 2011

Study Registration Dates

• First Submitted: July 18, 2011
• First Submitted That Met QC Criteria: July 18, 2011
• First Posted (Estimate): July 19, 2011

Study Record Updates

• Last Update Posted (Actual): June 23, 2022
• Last Update Submitted That Met QC Criteria: May 27, 2022
• Last Verified: May 1, 2022

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; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 1248.5; 2010-023167-17 (EudraCT Number: EudraCT)