moderate-to-severe persistent 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: Inclusion criteria at Visit -1 1.Male or female patients aged 12 to 65 years 2.Written informed consent signed by the patient or for patients younger than 18 years (adolescents) signed according to local requirements by one or both of the patient’s parent(s) or legal representative and by the patient, if applicable, prior to any protocol specific procedures 3.Medical history of moderate-to-severe persistent asthma (according to GINA) of at least 6 months duration 4.Regular use of ICS or ICS plus LABA over the 6 months preceding Visit -1 5.Regular treatment with high-dose ICS alone or low- to high-dose ICS plus LABA within the 4 weeks preceding Visit -1 (see Appendix V for daily dosages of ICS according to GINA) 6.FEV1 = 50% of the predicted value by the European Community for Coal and Steel (ECCS) after a washout period of at least 6 hours for rapid-acting beta 2-agonists (RABA) and at least 12 hours for LABA 7.Reversible and variable airflow limitation at Visit -1: At least 12% and 200 ml increase of FEV1 compared to baseline after the stepwise reversibility test 8.Ability to read and write and to fill in the patient diary and the patient’s device preference questionnaire 9.Ability to handle correctly the asthma monitor 10.Capable to handle and to inhale from the investigational devices Additional inclusion criteria at V0 11.FEV1 = 50% and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Intermittent or persistent mild asthma as defined by GINA 2.Evidence of any active concomitant pulmonary disease other than asthma, i.e. chronic bronchitis, COPD 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.Smoking habits: current smokers or smokers who stopped smoking less than 6 months before Visit -1 or former smokers with a history of = 10 pack-years. 11.Overdependence on RABA, i.e. frequency of RABA inhalation not consistent with controlled moderate-to-severe persistent asthma 12.Patients naive for inhaled corticosteroids 13.Change in asthma medication or regimen (other than inhalation of RABA) within 4 weeks preceding Visit -1 14.Administration of cromones within 4 weeks preceding Visit -1 15.Administration of oral, nasal, rectal, parenteral or depot corticosteroids within 4 weeks preceding Visit -1 16.More than 2 courses of oral corticosteroids within the last 12 weeks 17.Theophylline, leukotriene modifiers and anticholinergics within 4 weeks preceding Visit -1 18.Long-acting antihistamines within 1 week preceding Visit -1 (astemizole within 12 weeks) 19.Use of ß-blockers, non-potassium sparing diuretics or potent inhibitors of the cytochrome P450-3A4 system like ketoconazole, itraconazole, ritonavir within 4 weeks preceding Visit -1 20.Vaccination with live-attenuated virus within 2 weeks preceding Visit -1 21.Impaired adrenal cortex function 22.Severe renal or hepatic disease 23.Hypokalaemia uncorrected and/or serum potassium value on Visit -1 less than 3.5 mmol/L 24.Acute or history of severe cardiovascular disorders (New York Heart Association class II-IV heart failure, heart rhythm abnormalities) 25.Untreated or unstable hypertension 26.Known diabetes of all types 27.Hyperthyroidism not adequately controlled 28.Glaucoma 29.History of hypersensitivity to at least one of the active ingredients of the investigational products or the reliever medication 30.History of allergy to lactose or milk protein or – as judged by the investigator – of intolerance to small amounts of lactose 31.Presence of any other severe decompensated concomitant disease (endocrine, hematological, neurological, immunological) 32.Known active and significant pulmonary abnormalities as detected on available chest radiographs 33.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 the investigational drug or the reliever medication 34.Pregnant or nursing women 35.Females of childbearing potential (not surgically sterilized / hysterectomized or postmenopausal for at least 1 year), who are not using and not willing to use medically reliable methods of contraception for the entire study duration (such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices) 36.History of non-compliance with asthma management plan. 37.Suspected alcohol or drug abuse 38.Current participation in anothe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show therapeutic equivalence (i.e. non-inferiority) of Salmeterol/Fluticasone DPI HEXAL to SeretideTM AccuhalerTM in adolescent and adult patients with moderate-to-severe persistent asthma for both the low dose combination (50 µg/100 µg of salmeterol/fluticasone per actuation, 2x1 actuation per day) and the high dose combination (50 µg/500 µg of salmeterol/fluticasone per actuation, 2x1 actuation per day). Conclusion of non-inferiority will for both dose combinations be based on 2 primary efficacy variables for each dosage leven since the treatment effects for fluticasone are different from salmeterol: abolute change in FEV1 and FEV1 AUC 0-12 after 12 weeks of treatment relative to baseline FEV1.;Secondary Objective: Efficacy: Change in FEV1 from baseline (Visit 0) to Visit 3; Development of FEV1 and FEV1 % predicted over the course of the study; Mean change in morning pre-dose FEV1 and PEF from baseline to evaluation period; Development of FVC; Time to onset of action at Visit 6; Development of PEF over the course of the study; Change in asthma symptoms scores and total asthma symptoms score over time; Frequency of use of reliever medication; Incidence and severity of asthma exacerbations; Number of patients discontinuing the study due to asthma worsening ; Overall assessment of efficacy. Safety: Incidence and severity of AEs and drug-related AEs; Clinically relevant changes in laboratory parameters, vital signs, ECG and physical examination parameters; Incidence of patients with oral candidiasis or voice hoarseness; Clinically relevant changes in morning serum cortisol levels; Serum cortisol concentration-time profiles at Visit 6; Overall assessment of tolerability of the IP.;Primary end point(s): The primary aim of this study is to show therapeutic equivalence (i.e. non-inferiority) of Salmeterol/Fluticasone DPI HEXAL to SeretideTM AccuhalerTM in adolescent and adult patients with moderate-to-severe persistent asthma for both the low dose com | — |
Countries
Hungary, Lithuania
Outcome results
None listed