Persistent, moderate asthma MedDRA version: 9.1 Level: LLT Classification code 10003555 Term: Asthma bronchial
Conditions
Sponsors
Hexal AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: At Visit -1: 1. Male or female children aged 4 to 11 years 2. Written informed consent signed according to local requirements by one or by both patient’s parent(s) or legal representative prior to any protocol specific procedures 3. Medical history of persistent moderate asthma (according to GINA) of at least 6 months duration 4. Regular use of ICS or ICS plus LABA over the 6 months immediately prior to Visit -1 5. Regular treatment with •medium- to high-dose ICS or medium-dose ICS plus LABA (children =5 years) within the 4 weeks immediately prior to Visit -1 6. Ability to perform spirometric maneuvers with a forced expiratory time of at least 1 second 7. Patients aged 6-11 years capable of coordinating MDI actuation and inhalation 8. FEV1 greater than 60% of the predicted value by the European Community for Coal and Steel (ECCS) after a washout period of at least 6 hours for RABA and at least 12 hours for LABA 9. Reversible and variable airflow limitation: At least 12% increase of FEV1 15-20 min after inhalation of 200 µg salbutamol. Reversibility has to be demonstrated at Visit -1 or needs to be documented by valid spirometric results obtained within 6 months prior to Visit -1 10. Ability to read and write and to fill in the patient diary by the patient or by patient’s parent(s) or legal representative 11. Ability to handle correctly the peak flow meter and the metered-dose inhalers with/without spacer At Visit 0: 1. FEV1 greater than 60% and less than 80% of the predicted value by the European Community for Coal and Steel (ECCS) after a washout period of at least 6 hours for RABA (reliever medication) 2. FEV1 within +/- 15% of the value obtained at Visit -1 3. At least 2 of the following criteria fulfilled during the last 7 days of the run-in period: 3.1. Nighttime symptom score (diary card rating of asthma symptoms) is at least 1 on at least 1 day 3.2. Daytime symptom score (diary card rating of asthma symptoms) is at least 1 on at least 3 days 3.3. Use of RABA on at least 4 days Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: At V-1: 1. Intermittent or persistent mild or severe asthma as defined by GINA 2. Evidence of any active concomitant pulmonary disease other than asthma, i.e. chronic bronchitis 3. Respiratory tract infection (including sinusitis) and middle ear infection within 4 weeks prior to Visit -1 4. Acute asthma exacerbation within 4 weeks preceding Visit -1 5. Acute asthma exacerbation requiring hospitalization or emergency room visit within 12 weeks preceding Visit -1 6. History of life-threatening acute attacks or intubation for asthma 7. History of seasonal asthma exacerbation 8. History of paradoxical bronchospasm after inhaled asthma therapy 9. Active or inactive lung tuberculosis 10. Overdependence on RABA, i.e. frequency of RABA inhalation not consistent with persistent moderate asthma 11. Patients naive for inhaled corticosteroids 12. Change in asthma medication or regimen (other than inhalation of RABA) within 4 weeks preceding Visit -1 13. Administration of cromones within 4 weeks preceding Visit -1 14. Administration of oral corticosteroids within 4 weeks preceding Visit 1 15. More than 2 courses of oral corticosteroids within the last 12 weeks 16. Allergen-specific immunotherapy within the last 12 weeks 17. Long-acting antihistamines within 1 week preceding Visit -1 (astemizole within 12 weeks) 18. Use of beta-blockers or potent inhibitors of the cytochrome P450-3A4 system like ketoconazole, itraconazole, ritonavir within 4 weeks preceding Visit -1 19. Vaccination with live-attenuated virus within 2 weeks preceding Visit -1 20. Impaired adrenal cortex function 21. Severe renal or hepatic disease 22. Hypokalemia uncorrected and/or serum potassium value on Visit -1 less than 3.5 mmol/L 23. Acute or history of severe cardiovascular disorders (e.g. heart rhythm abnormalities) 24. Untreated or unstable hypertension 25. Known diabetes 26. Hyperthyroidism not adequately controlled 37. Glaucoma 28. History of hypersensitivity to one or both of the active ingredients or to any other component of the preparations or reliever medication 29. Presence of any other severe decompensated concomitant disease (endocrine, hematological, neurological, immunological) 30. Known active and significant pulmonary abnormalities as detected on chest radiographs 31. Other relevant medical condition, ECG abnormality, or laboratory profile that might compromise the patient’s safety, compliance, or interfere with the evaluation or preclude completion as judged by the investigator or other contraindication to test drug. 32. Females of childbearing potential, not willing to abstain from sexual activities throughout complete duration of participation in the study 33. History of non-compliance with asthma management plan 34. Current participation in another investigational drug study, or participation in any clinical study involving an investigational drug within 3 months prior to Visit -1 35. Lack of sufficient co-operation or compliance or existing psychosocial problems 36. Legal incapacity of the patient’s parent(s) or legal representative or other circumstances rendering the patient’s parent(s) or legal representative unable to understand the nature, scope and possible consequences of the study At V0: 1. Acute respiratory tract infection during run-in period 2. Severe asthma exacerbation during run-in period 3. Any intake of asthma medication other than the inhalation of the supplied reliever medication during run-in period 4. Use of more than 6 actuations
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): - FEV1 at the end of the 12-week study period (Visit 4) compared with baseline (Visit 0) - area under the 4-hour serial FEV1 curve (AUC0-4) at the end of the 12-week study period (Visit 4) relative to baseline FEV1 (Visit 0);Main Objective: To show therapeutic equivalence of Salmeterol/Fluticasone MDI HEXAL (25 µg/50 µg per actuation) to SeretideTM 50 (25 µg/50 µg per actuation, Glaxo Wellcome UK Ltd.). Equivalence or non-inferiority will be concluded if the resulting 97.5% confidence interval for the difference between the two treatment groups with regard to the change in FEV1 (Visit 4 minus Visit 0) and the area under the 4-hour serial FEV1 curve (AUC0-4) at Visit 4 relative to baseline FEV1 (Visit 0) is completely contained within the acceptance ranges [ -12 %; 8] and [ 80 %; 8], respectively.;Secondary Objective: Efficacy: Change in FEV1 from V0 to V2; Development of FEV1 and FEV1% over course of study; Change in morning pre-dose PEF from baseline to evaluation period; Development of the weekly morning and evening PEF and of FVC over course of study; Change in day/nighttime symptoms score over time; Frequency of reliever use, Incidence and severity of asthma exacerbations; #patients discontinuing the study due to asthma worsening; Overall assessment of efficacy Safety: Incidence/severity of AEs and drug related AEs; Morning serum cortisol at last study visit; 16-hour urinary free cortisol levels, Clin. relevant changes in lab parameters, vital signs, ECGs and physical exam parameters from V-1 to V 4; plasma levels of fluticasone and salmeterol at Visit 4; Incidence of oral candidiasis or voice hoarseness; Overall assessment of tolerability of the investigational product Additional: #days the child has been sick/needed home care and days missed by the parent(s) due to childcare | — |
Countries
Lithuania
Outcome results
None listed