A MULTICENTRE, RANDOMISED, DOUBLE BLIND, DOUBLE-DUMMY PARALLEL-GROUP STUDY INVESTIGATING THE EFFICACY AND SAFETY OF THREE DIFFERENT DOSES OF TACROLIMUS INHALATION AEROSOL AND A STANDARD DOSE OF INHALED CORTICOSTEROID (ICS) IN PATIENTS WITH MODERATE PERSISTENT ASTHMA - Tacrolimus MDI versus ICS

Conditions: Asthma
MedDRA version: 7.0Level: LLTClassification code 10003553

Registration Number: EUCTR2004-002079-18-HU

Lead Sponsor: Fujisawa GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 360

Inclusion Criteria

Inclusion Criteria for the Run-in period
1) Male or female patients between 18 and 70 years of age inclusive
2) Patients must have a diagnosis of asthma for at least 6 months
3) Patients must have been pre-treated with inhaled corticosteroids (daily ICS
dose of up to 800 mcg budesonide, 500 mcg fluticasone, 1000 mcg beclomethasone or 400 mcg beclomethasone extra-fine aerosol) for at least 6 months prior to study entry.
4) Patients must use a short acting ß2-agonist more than twice a day for at least four days per week due to asthma symptoms
5) Patients must have an FEV1 = 60 to 80 % of the predicted value
6) Patients must have a reversibility of at least 15 % and at least a 200ml increase in their FEV1 within 30 minutes of receiving two puffs of a short acting ß2-agonist (salbutamol) at the screening visit
7) Patients on immunotherapy must have been on a stable dose for one month prior to study entry and remain on that stable dose during the conduct of the study
8) Female patient of child bearing potential must have a negative serum pregnancy test prior to enrolment and must agree to practice effective birth control during the study.
9) Patient is capable of understanding the purpose and risks of the study, has been fully informed and has given written informed consent to participate in the study.

Inclusion Criterion for randomisation
1) FEV1 at baseline does not differ more than 15 % from the value obtained at
the screening visit and FEV1 is still = 80% of the predicted.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Systemic/oral corticosteroids within six weeks prior to study entry
2) Respiratory infections within 2 weeks prior to study entry
3) History of tuberculosis
4) Hospitalisation (> 24 hours) for an asthma exacerbation within 90 days prior to
study entry or has ever been intubated for an asthma exacerbation
5) Moderate to severe liver disease as defined by one or more of the following at
Screening:
-Aspartate transaminase (AST) or alanine transaminase (ALT) > 2 times the
upper limit of normal (ULN)
-Alkaline phosphatase > 3 times the ULN
6) Creatinine > 1.5 times the ULN
7) Haemoglobin < 9.0 g/dl, WBC < 3000 cells/mm3 or a platelet count <
100.000/mm3
8) Intake of a long-acting ß2-agonist (e.g. salmeterol or formoterol) within 24 hours
prior to study entry
9) Patient currently smokes or has discontinued smoking within 6 months prior to
the study entry or has a smoking history of = 10 pack years*
10) Patient has a history of alcohol abuse within the last 5 years
11) Patient has used leukotriene modifiers within 4 weeks prior to study entry
12) Patient has used monoclonal antibodies for the treatment of asthma, methotrexate, gold salts, cyclosporine, tacrolimus (topical or systemic) or azathioprine within 3 months prior to study entry
13) Patient is receiving beta-receptor blocking drugs (including eye-drops)
14) Patient is receiving any prohibited concomitant medication
15) Patient has an advanced, severe or unstable disease of any type other than
moderate asthma (e.g. advanced chronic heart failure NYHA class III or IV, arrhythmia, subvalvular aortic stenosis, severe hypertension, aneurysm, ischemic heart disease, AV block III, uncontrolled diabetes mellitus)
16) Patient has a haematologic or solid malignancy diagnosed within five years
prior to study entry. (Note: Patient with localized skin cancer, i.e. basal cell or
squamous cell carcinoma, may participate in the study. Patient who has
received adequate treatment for localized cancer may be allowed to participate
in the study subject to approval by the Medical Monitor.)
17) Patient has any significant concomitant disease in the opinion of the investigator
18) Patient is known to be HIV positive
19) Patient is pregnant or a breast-feeding mother
20) Patient is unlikely to comply with the visits scheduled in the protocol.
21) Patient is participating or has participated in another investigational drug trial or
is receiving or has received an investigational drug within the last 28 days before entry into this study
22) Patient has a known hypersensitivity to macrolides, the active substances or the
excipients of the study medication
23) Patient has been previously enrolled in this study

*Definition of one pack year: Smoking of 20 cigarettes daily for one year or 10
cigarettes daily for two years etc.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate a statistically significant trend across the tacrolimus doses. ;Secondary Objective: - To determine the efficacy of 3 dose levels of tacrolimus aerosol in comparison <br>to a standard dose of inhaled corticosteroid in ICS pretreated patients with <br>moderate persistent asthma. <br>- To evaluate the safety and tolerability of different doses of tacrolimus aerosol <br>in comparison to a standard dose of inhaled corticosteroid. <br>- To obtain tacrolimus blood concentration data in patients with moderate persistent asthma at baseline, week 6, and 12. ;Primary end point(s): Absolute change in patient´s maximum value of FEV1 from baseline (day 1) to week 12 / end of randomised treatment

Secondary Outcome Measures