Clinical trial NCT01396278: Study on BI 54903 (Inhaled Corticosteroid) Administered Twice Daily Via Respimat Inhaler in Patients With Asthma Inadequately Controlled on Medium Dose Inhaled Corticosteroid (ICS).
Official title: A Randomised, Double-blind, Double-dummy, Active-controlled, Parallel-group Study to Assess and Compare Efficacy and Safety of an 8-week Treatment With BI 54903 at Doses of 90.9, 181.8 and 363.6 µg b.i.d. Administered Via Respimat® Inhaler and Fluticasone Propionate HFA MDI 440 µg b.i.d. in Patients With Asthma Inadequately Controlled on Medium Dose ICS Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-07-18
Enrollment: 9
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to assess and compare efficacy and safety of BI 54903 at three different dosages (b.i.d)., fluticasone propionate hydrofluoroalkane (HFA) metered dose inhaler (MDI) at a dose of 440 mcg b.i.d and low dose fluticasone propionate 88 mcg b.i.d. over an 8-week treatment period in asthmatic patients aged 12 to 65 years inadequately controlled medium dose ICS therapy as demonstrated by a decrease in forced expiratory volume in one second (FEV1) range 10 to 25 % and an asthma control questionnaire-6 (ACQ-6) equal or greater than 1.5 at time of randomisation.


Eligibility criteria: Inclusion criteria:

1. Must be willing and able to give informed consent.
2. Male and female patients aged at least 12 to 65 years.
3. 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 high-dose ICS with long-acting beta 2-agonist (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 ACQ-6 mean score of less than 1.5 at the pre-screening Visits 1and 2.
6. 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 .
7. Patients must be able to use Respimat® inhaler and MDI correctly
8. 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.

   To enter treatment period following additional criteria have to be met:
9. All patients must have an improvement in 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 HFA MDI as demonstrated at Visit 1 or during one of the visits during run-in period.
10. During the run-in period (at the same clinic visit) all patients must be both symptomatic (ACQ-6 mean score equal to or greater than 1.5) and have shown a decrease in morning pre-bronchodilator FEV1 not less than 10% and less than or equal to 25% from pre-screening baseline FEV1 at Visit 2.

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) that may, in the opinion of the investigator, result in any of the following: (i) put the patient at risk because of participation in this trial or (ii) influence the results of the trial or (iii) cause concern regarding the patient´s ability to participate in the trial.
2. Patients with a clinically relevant, abnormal screening haematology and/or blood chemistry finding, if the abnormality indicates a significant disease as defined in exclusion criterion no. 1.
3. Patients with a history of upper respiratory tract infection (URTI) or lower respiratory tract infection (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 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 or 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-IgE-antibodies (e.g. omalizumab, Xolair®) or other immune system modulating antibodies such as tumor necrosis factor-alpha blockers (TNF-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 ß-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.
20. Patients who have been treated with leukotriene modifiers, chromones or theophylline within two weeks prior to Visit 1.
21. Patients who have been treated with tiotropium within 3 weeks prior to Visit 1.

Primary outcomes:
measure: Mean Change From 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)
timeFrame: At baseline and week 8
Secondary outcomes:
measure: Mean Changes From Randomization Baseline in Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Forced Vital Capacity (FVC) After 2, 4 and 8-week Treatment Periods
timeFrame: At baseline and week 2, 4, 8.
measure: Mean Changes From Randomization Baseline in Trough (Morning Pre-dose and Pre-rescue Bronchodilator) FEV1 After 2 and 4-week Treatment Periods
timeFrame: At baseline and week 2 and 4.
measure: Mean Pre-dose (and Pre-rescue) Peak Expiratory Flow (PEF) as Assessed Via Asthma Monitor2+ (AM2+) in the Morning and Evening of the Last Week of the 8-week Treatment Period
timeFrame: At week 8.
measure: Mean Rescue Medication Use (Daytime and Night-time) as Assessed Via AM2+ in the Morning and Evening of the Last Week of the 8-week Treatment Period
timeFrame: At week 8.
measure: Mean Change From Randomisation Baseline in ACQ-6 Scores at Subsequent Study Visits
timeFrame: At baseline and week 2, 4, 8.
measure: Mean Change From Randomisation Baseline in Asthma Quality of Life Questionnaire (AQLQ(S)+12) Scores at Subsequent Study Visits
timeFrame: At baseline and week 2, 4, 8.
measure: Time to Withdrawal Due to First Asthma Exacerbation
timeFrame: At week 8.
measure: Mean Change From Randomization Baseline in Through (Morning Pre-dose and Pre-rescue Bronchodilator) FEF 25-75 After 2, 4 and 8-week Treatment Periods
timeFrame: At baseline and week 2, 4 and 8.
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: 1248.7.01047 Boehringer Ingelheim Investigational Site
state: California
city: Fullerton
country: United States
facility: 1248.7.01023 Boehringer Ingelheim Investigational Site
state: California
city: Long Beach
country: United States
facility: 1248.7.01038 Boehringer Ingelheim Investigational Site
state: California
city: Mission Viejo
country: United States
facility: 1248.7.01004 Boehringer Ingelheim Investigational Site
state: California
city: Palmdale
country: United States
facility: 1248.7.01028 Boehringer Ingelheim Investigational Site
state: California
city: Stockton
country: United States
facility: 1248.7.01044 Boehringer Ingelheim Investigational Site
state: California
city: Centennial
country: United States
facility: 1248.7.01015 Boehringer Ingelheim Investigational Site
state: Colorado
city: Aventura
country: United States
facility: 1248.7.01035 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1248.7.01022 Boehringer Ingelheim Investigational Site
state: Florida
city: Columbus
country: United States
facility: 1248.7.01051 Boehringer Ingelheim Investigational Site
state: Georgia
city: Savannah
country: United States
facility: 1248.7.01052 Boehringer Ingelheim Investigational Site
state: Georgia
city: Eagle
country: United States
facility: 1248.7.01011 Boehringer Ingelheim Investigational Site
state: Idaho
city: Oak Lawn
country: United States
facility: 1248.7.01055 Boehringer Ingelheim Investigational Site
state: Illinois
city: Baltimore
country: United States
facility: 1248.7.01019 Boehringer Ingelheim Investigational Site
state: Maryland
city: North Dartmouth
country: United States
facility: 1248.7.01039 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Ypsilanti
country: United States
facility: 1248.7.01037 Boehringer Ingelheim Investigational Site
state: Michigan
city: Rolla
country: United States
facility: 1248.7.01056 Boehringer Ingelheim Investigational Site
state: Missouri
city: Warrensburg
country: United States
facility: 1248.7.01036 Boehringer Ingelheim Investigational Site
state: Missouri
city: Omaha
country: United States
facility: 1248.7.01020 Boehringer Ingelheim Investigational Site
state: Nebraska
city: Berlin
country: United States
facility: 1248.7.01049 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Ocean City
country: United States
facility: 1248.7.01026 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Trenton
country: United States
facility: 1248.7.01054 Boehringer Ingelheim Investigational Site
state: New Jersey
city: High Point
country: United States
facility: 1248.7.01031 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: 1248.7.01045 Boehringer Ingelheim Investigational Site
state: Ohio
city: Portland
country: United States
facility: 1248.7.01021 Boehringer Ingelheim Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: 1248.7.01013 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: 1248.7.01040 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Upland
country: United States
facility: 1248.7.01012 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: 1248.7.01048 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Austin
country: United States
facility: 1248.7.01050 Boehringer Ingelheim Investigational Site
state: Texas
city: Live Oak
country: United States
facility: 1248.7.01002 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1248.7.01032 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1248.7.01046 Boehringer Ingelheim Investigational Site
state: Texas
city: Waco
country: United States
facility: 1248.7.01001 Boehringer Ingelheim Investigational Site
state: Texas
city: Murray
country: United States
facility: 1248.7.01025 Boehringer Ingelheim Investigational Site
state: Utah
city: Alexandria
country: United States
facility: 1248.7.01053 Boehringer Ingelheim Investigational Site
state: Virginia
city: Tacoma
country: United States
facility: 1248.7.01030 Boehringer Ingelheim Investigational Site
state: Washington
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: