Efficacy and safety of Salmeterol/Fluticasone MDI HEXAL versus SeretideTM EvohalerTM in adolescent and adult patients with moderate-to-severe persistent asthma: A 12-week, multicenter, randomized, double-blind, double-dummy, parallel-group study

Phase 1

Conditions: moderate-to-severe persistent asthma
MedDRA version: 9.1Level: LLTClassification code 10003555Term: Asthma bronchial

Registration Number: EUCTR2007-005235-29-PL

Lead Sponsor: HEXAL AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 480

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 also by the parent(s) or by the legal guardian 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 immediately prior to Visit -1
5. Regular treatment with high-dose ICS alone or low- to high-dose ICS plus LABA within the 4 weeks immediately prior to 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 least 15% increase of FEV1 15-20 min after RABA inhalation (200 µg salbutamol). Reversibility has to be demonstrated at Visit -1 or needs to be documented by valid spirometric results, obtained with 200-400µg of salbutamol, within 6 months prior to Visit -1
8. Ability to read and write and to fill in the patient diary
9. Ability to handle correctly the metered-dose inhalers and the peak flow meter

At Visit 0:
1. FEV1 = 50% and < 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 pre-inhalation 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 for symptomatic relief (not prophylaxis) 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) yes
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

At Visit -1:
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) 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, 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, 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 beta-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
21. Impaired adrenal cortex function
22. Severe renal or hepatic disease
23. Hypokalemia 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 one or both of the active ingredients or to any other component of the preparations or reliever medication
30. Presence of any other severe decompensated concomitant disease (endocrine, hematological, neurological, immunological)
31. Known active and significant pulmonary abnormalities as detected on available chest radiographs
32. 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
33. Pregnant or nursing women
34. 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)
35. Necessity to use a spacer device for inhalation
36. History of non-compliance with asthma management plan
37. Suspected alcohol or drug abuse
38. Current participation in another investigational drug study, or participation in any clinical study involving an investigational drug

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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