A two week treatment, multi-center, randomized, openlabel, assessor blinded, parallel group study of QAE397 400 g, o.d. QAE397 1200 g o.d. , budesonide 100 g, o.d. , or budesonide 400 g, b.i.d. delivered via SDDPI in moderate to severe asthmatic patients - ND

• Conditions: asthma; MedDRA version: 9.1Level: LLTClassification code 10003553Term: Asthma

• Registration Number: EUCTR2006-003997-89-IT
• Lead Sponsor: OVARTIS FARMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-01
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1. Male and female patients 18-75 years of age, who have signed an informed consent form. 2. Patients with moderate to severe asthma diagnosed according to GINA guidelines Step 3 and above and who have used bronchodilator treatment on a regular or on-demand basis, 3. Patients who have been receiving daily treatment with a daily dose of 8805;1000 g BDP or equivalent in a stable regimen for at least 1 month prior to visit 1, 4. Patients whose FEV1 at visit 1 is 8805;60 of the predicted normal value after appropriate washout from bronchodilators 5. Evidence of asthma, demonstrated by one of the following Demonstration of 8805;12 reversibility and 200-mL improvement of FEV1 using a standard dose of salbutamol up to 400 g within 30 minutes. This criterion for FEV1 will have to be demonstrated after a washout period of at least 6 h during which no short-acting 946;2-agonist has been inhaled, or 24 hours for long-acting 946;2-agonist, such as formoterol, prior to the evaluation Historical reversibility as outlined above, documented within 6 months of visit 1 Documented bronchial hyper-reactivity to 8804;8 mg/mL methacholine or histamine challenge. 6. Women of child-bearing potential WOCBP , defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal 12 months of natural spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels 40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception double-barrier methods any double combination of IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap . 7. Body Mass Index between 19 and 30. Body weight should be less than 100 kg. 8. Able to provide written informed consent prior to study participation. Subject information and consent forms generated by the investigator must be approved by the sponsor prior to submission to the Ethics Committee EC /Institutional Review Board IRB . A copy of the subject information and consent forms approved by the EC/IRB must be forwarded to the sponsor prior to study initiation. 9. Able to communicate well with the investigator and comply with the requirements of the study. 10. Patients who demonstrate the ability to produce adequate sputum samples for differential cell counts minimum 75 mg of selected sputum/120,000 total inflammatory cells; 50 viability, 20 squamous epithelial cell content at visit 1. 11. Patients must have 0.6 sputum eosinophils at baseline to enter the study.
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. Pregnant or nursing lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test 5 mIU/ml . 2. Patients who have used tobacco products within the 6 month period prior to visit 1, and who have a smoking history of greater than 10 pack years defined as the number of packs of 20 cigarettes smoked per day multiplied by the number of years the patient smoked . 3. Patients who suffer from COPD. 4. Patients who have used parenteral or oral corticosteroids within 3 months of visit 1. 5. The following medications should not be used unless they have been stabilized for at least one month prior to visit 1 Cromoglycate Nedocromil Ketotifen Leukotriene antagonists 6. Patients being treated with omalizumab. 7. Patients who are receiving therapy that could interact with steroids, such as enzyme inhibitors macrolide antibiotics, antifungal therapy or inducers anticonvulsants, rifampin . 8. Use of oral contraceptives containing prednisolone, the active metabolite of prednisone. 9. Patients who have been hospitalized have been admitted to a hospital for observation or treatment in the 6 months prior to visit 1 or had emergency room treatment for an acute asthma attack in the 3 months prior to visit 1. 10. Patients who have had a respiratory tract infection within 1 month prior to visit 1. 11. Patients with clinically significant conditions that might compromise patients safety or compliance. 12. Medical conditions History of clinically significant drug allergy; Any significant medical condition that in the opinion of the Investigator may compromise subject safety, subject compliance, interfere with evaluations, or preclude completion of the trial. For example, a history of any pulmonary disorder other than asthma. 13. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of enrollment, whichever is longer 14. Any surgical or medical condition which might significantly affect the distribution, metabolism or excretion of the drug. 15. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation. 16. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing or longer if required by local regulation. 17. Significant illness within the two weeks prior to dosing. 18. A past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome. 19. History of autonomic dysfunction e.g. history of fainting, orthostatic hypotension, sinus arrhythmia. 20. History of immunocompromise, including a positive HIV test result. 21. History of drug or alcohol abuse within the 12 months prior to dosing. 22. A known hypersensitivity to budesonide. 23. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin 24. Fertile males, defined as all males physiologically capable of having offspring UNLESS the patient and his partner agree to comply with acceptable contraception, including approved methods of double barrier contraception. 25. Inability to produce an adequate sputum sample as defined in the inclusion criteria.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to determine the effect of once daily QAE397 400 g or 1200 g compared to once daily budesonide 100 g in moderate to severe asthma patients on sputum eosinophilia after two weeks of treatment.;Secondary Objective: The secondary objective of this study is to evaluate the effect of once daily QAE397 400 g or 1200 g compared to once daily budesonide 100 g , or twice daily budesonide 400 g , in moderate to severe asthma patients on PC20 levels after methacholine MCh challenge, Exhaled Nitric Oxide, FVC and FEV1 after two weeks of treatment. Also, to estimate the effect of QAE397 400 g or 1200 g and budesonide 400 g bid on sputum eosinophilia after assay sensitivity of the study has been established.;Primary end point(s): The eosinophil count reading.