A multicentre, randomized, open-label, cross-over equivalence study to compare the pharmacodynamic properties, safety, and tolerability of a new combination dry powder of fluticasone propionate and salmeterol (ComboFS) twice daily and the reference product Seretide® Diskus® in patients with asthma
- Conditions
- MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]asthma
- Registration Number
- EUCTR2019-004429-26-PL
- Lead Sponsor
- PRZEDSIEBIORSTWO FARMACEUTYCZNE LEK-AM SPÓLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 200
1.Male and female patients aged 18 years and older
2.Patient/Subject or legal representative has signed the ICF prior to any protocol specific procedure
3.Symptomatic patients suffering from unstable asthma partly controlled according to international recommendations provided by GINA 2019:
a.with 60% b.which fulfill at least 2 of the following criteria during the last 7 days of the run-in period:
i.symptom score (diary card rating of asthma symptoms) =2 on any 2 days
ii.use of short acting beta2-agoinst (rescue medication) more than twice daily on any 2 days
iii.night-time diary card symptom score of =1 on one occasion
iv.diurnal variation in PEF of more than 30% on at least 1 day
c.which have been stable for 6 months prior to visit 2 (Baseline)
4.Patients with at least 12% increase of FEV1 and a minimum of 200 ml of due value approx. 15-20 min after a short acting ß2-agonist inhalation (400 µg salbutamol). Reversibility test has to be demonstrated at Visit 1 (week -2) (the test can be repeated during seven following days) or at Visit 2 or has to be documented within 12 months prior to Visit 1by using spirometry.
5.5.Patients who have been treated before the study with fluticasone propionate + salmeterol combination in the dose of 500 mcg + 50 mcg twice a day will be randomized to receive either ComboFS 250 mcg/25 mcg or Seretide® Diskus® 500/50 mcg/dose.
Patients who have been treated before the study with fluticasone propionate + salmeterol combination in the dose of 250 mcg + 25 mcg or 250 mcg + 50 mcg twice a day will be randomized to receive either ComboFS 125 mcg/25 mcg vs. Seretide® Diskus® 250/50 mcg/dose.
6.Patients must be able to read and write and to fill in the patient’s diary.
7.Patients must be able to handle the metered dose inhalers and a mini-Wright peak flow meter.
8.Patients have to be in a stable general condition.
ECG safety criteria:
The subject must have no ECG abnormalities that would, in the opinion of investigator, compromise subject safety, or significantly affect subject’s ability to complete the trial. As such, the investigator will determine the clinical significance of any ECG abnormality and determine if a subject is precluded from entering the study. At Visit 1 (Screening and Run-in Visit), ECG safety criteria must be:
•QT interval corrected for heart rate (QTc) or QT interval corrected for heart rate according to Fridericia formula (QTcF) <450 msec or
•QTc <480 msec for subjects with bundle branch block
Investigators will be responsible for ensuring appropriate clinical interpretation of ECGs.
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Disease specific criteria
1.Acute upper respiratory infection within 4 weeks prior to Visit 2 (Baseline)or during screening/run-in period.
2.Acute lower respiratory infection within 12 weeks prior to Visit 2 (Baseline) or during screening/run-in period.
3.Unstable asthma as evidenced by
a.any deterioration of asthma / acute asthma exacerbation requiring hospitalization or emergency room visit or
b.any change in asthma therapy (other than inhalation of short-acting ß2 agonists) within 6 months preceding Visit 2 (Baseline)
4.Previous history of life-threatening acute attacks or intubation for asthma
5.History of seasonal asthma exacerbation,
6.Active or inactive lung tuberculosis or evidence of any active concomitant pulmonary disease other than asthma, i.e. chronic bronchitis, COPD,
7.Smoking within 6 months prior to visit 2 or during the study; for ex-smokers a smoking history of more than 10 pack-years (the equivalent of one pack per day for 10 years)
Previous / Concomitant medication
8.Patients naive for inhaled corticosteroids
9.More than 4 short courses of oral corticosteroids within the last year before visit 2 or any oral steroids within 6 months prior to visit 2.
10.Allergen immunotherapy in escalation dose regime within 3 months preceding visit 2
11.Within 3 days preceding to visit 1 or planned to be applied during the trial (after Visit2) use of:
a.leukotriene antagonists, inhaled cromolyn sodium; oral or parenteral corticosteroids (oral steroids are permitted for one period of maximal 14 days during the trial), long acting ß2-agonists (other than study medication), theophylline, inhaled anti-cholinergics,
b.ß-blockers or potent inhibitors of the cytochrome P450-3A4 system e.g. ketoconazole, itroconazole (Selective ß-blockers i.e. Nebivolol or Bisoprolol can be taken),
c.Vaccination with live-attenuated virus; exception: oral polio vaccine (Sabin) is allowed
12.Use of short-acting ß2 agonists within 6 hours preceding Visit 2 or planned to be applied during the trial except to rescue medication;
Other diseases and conditions
13.Impairment of adrenal cortex function, severe renal or hepatic disease.
14.Acute or history of severe cardiovascular disorders including cardiac arrhythmia, tachycardia (more than 120), idiopathic subvalvular coarctation of the aorta.
15.Serum potassium value on screening visit ? 3,5 mmol/L
16.Not controlled diabetes mellitus.
17.Not controlled hyperthyroidism.
18.History of paradoxical bronchospasm after inhalative asthma therapy.
19.History of hypersensibility to one or both of the active ingredient or to any other component of the IMP,Seretide® Diskus®, or rescue medication.
20.Presence of any other severe decompensated concomitant systemic disease (cardiovascular, endocrine, hematological, neurological, immunological) as judged by the investigator.
21.Other significant 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
Special restrictions for females
22.Pregnant or nursing women
23.Females of childbearing potential, 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, unless they are surgically sterilized / hysterectomized or
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