A 12-week, multinational, randomised, double blind, double dummy, 4-arm parallel-group study comparing the efficacy and safety of CHF 1535 (fixed combination of beclomethasone dipropionate + formoterol fumarate) 100 + 6 µg/actuation inhalation powder, administered via the NEXT™ inhaler, versus CHF 1535 (fixed combination of beclomethasone dipropionate + formoterol fumarate) 100 + 6 µg/actuation, via HFA pressurised inhalation solution, in moderate to severe symptomatic asthmatic patients aged = 12 years under treatment with inhaled corticosteroids

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000401-11-DE
• Date of registration: 04/08/2008
• Prospective Registration: Yes
• Primary sponsor: CHIESI Farmaceutici S.p.A
• Public title: A 12-week, multinational, randomised, double blind, double dummy, 4-arm parallel-group study comparing the efficacy and safety of CHF 1535 (fixed combination of beclomethasone dipropionate + formoterol fumarate) 100 + 6 µg/actuation inhalation powder, administered via the NEXT™ inhaler, versus CHF 1535 (fixed combination of beclomethasone dipropionate + formoterol fumarate) 100 + 6 µg/actuation, via HFA pressurised inhalation solution, in moderate to severe symptomatic asthmatic patients aged = 12 years under treatment with inhaled corticosteroids
• Scientific title: A 12-week, multinational, randomised, double blind, double dummy, 4-arm parallel-group study comparing the efficacy and safety of CHF 1535 (fixed combination of beclomethasone dipropionate + formoterol fumarate) 100 + 6 µg/actuation inhalation powder, administered via the NEXT™ inhaler, versus CHF 1535 (fixed combination of beclomethasone dipropionate + formoterol fumarate) 100 + 6 µg/actuation, via HFA pressurised inhalation solution, in moderate to severe symptomatic asthmatic patients aged = 12 years under treatment with inhaled corticosteroids
• Date of first enrolment: 31/10/2008
• Target sample size: 831
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000401-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Bulgaria, Czech Republic, Germany, Hungary

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent obtained from the patient and/or the parents/legal representatives (according to the local laws)
2. Outpatients of both sexes, aged = 12 years
3. Clinical diagnosis of moderate to severe symptomatic asthma treated with a stable daily dose of inhaled corticosteroids < 2000 µg BDP or equivalent for at least 4 weeks prior to inclusion.
4. Forced expiratory volume in the first second (FEV1) > 40% and < 80% of the predicted normal values following adequate wash-out from bronchodilators.
5. A documented positive response to the reversibility test at the screening visit, defined as ?FEV1 = 12% and = 200 mL over baseline, 30 minutes after 400 µg salbutamol pMDI (ATS/ERS taskforce 2005).
6. Evidence for “partly controlled” asthma in the 2 weeks before inclusion according to the Classification of Asthma Severity and Levels of Asthma Control of the Global Strategy for Asthma Management and Prevention (GINA revised 2006) i.e. one or more of the following, other than FEV1 < 80% of the predicted normal value:
•daytime symptoms more than twice / week;
•any limitations of activities or nocturnal symptoms / awakening;
•need for reliever/rescue treatment more than twice / week.
7. Patients free of long-acting ß2-agonists (LABAs) treatment at least for 2 weeks before the screening visit;
8. Daily dose of previous inhaled corticosteroids (ICS) treatment:
•< 2000 µg of CFC BDP or “non-extrafine” BDP
•< 800 µg of BDP “extrafine” HFA
•< 1600 µg of budesonide
•< 1000 µg of fluticasone
•< 2000 µg of flunisolide
•<1200 µg of mometasone
•< 1280 µg of ciclesonide
9. A minimum inspiratory flow = 40 L/min evaluated with the In-Check Oral (at Visit 1).
10. Non-smokers or ex smokers with a cumulative tobacco exposure less than 5 pack years and who have stopped smoking since more than 1 year.
11. A cooperative attitude and ability to be trained in the proper use of a pMDI and a NEXT™DPI.
12. At visit 2 the “partly controlled” asthma will be checked with the Asthma Control Questionnaire to check symptoms in the last 7 days (ACQ score = 1.5).
Evidence for “partly controlled” asthma in the 2 weeks run-in period according to the Classification of Asthma Severity and Levels of Asthma Control of the Global Strategy for Asthma Management and Prevention (GINA revised 2006) i.e. one or more of the following, other than FEV1 < 80% of the predicted normal value:
•daytime symptoms more than twice / week;
•any limitations of activities or nocturnal symptoms/awakening
•need for reliever/rescue treatment more than twice / week.
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) 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 urinary ß-HCG laboratory test (> 5 IU/ml)
2. Women of child-bearing potential, 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/ml
•or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy
•or are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). For females aged 12 to 17 years acceptable methods of contraception may include total abstinence at the discretion of the investigator. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation.
3. Significant seasonal variation in asthma or asthma occurring only during episodic exposure to an allergen or a chemical sensitizer;
4. History of near fatal asthma (e.g. brittle asthma, hospitalisation for asthma exacerbation in Intensive Care Unit);
5. Occurrence of asthma exacerbations or respiratory tract infections in the 6 weeks preceding the screening visit;
6. Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (updated 2006);
7. History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency;
8. Diagnosis of restrictive lung disease
9. Patients treated with oral or parenteral corticosteroids in the previous 2 months (3 months for parenteral depot corticosteroids);
10. Intolerance or contra-indication to treatment with ß2-agonists and/or inhaled corticosteroids;
11. Allergy to any component of the study treatments;
12. Any change in the dose, schedule, formulation or product of an inhaled corticosteroid in the 4 weeks prior to screening visit;
13. Having received an investigational drug within 2 months before the screening visit;
14. Inability to comply with study procedures or treatment;
15. Significant medical history of and/or treatments for cardiac, renal, neurological, hepatic, endocrine diseases, or any laboratory abnormality indicative of a significant underlying condition, that may interfere with patient’s safety, compliance, or study evaluations, according to the investigator’s opinion;
16. Any patient with active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized basal cell carcinoma (without metastases) of the skin is acceptable.
17. Patients with abnormal QTc at screening visit (> 450 msec-Bazett formula).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to severe symptomatic asthmatic patients aged = 12 years under treatment with inhaled corticosteroids (< 2000 µg BDP or equivalent).
MedDRA version: 9.1 Level: LLT Classification code 10003553 Term: Asthma

Intervention(s)

Product Name: CHF 1535 NEXT(TM) DPI
Product Code: CHF 1535 NEXT
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: beclometasone dipropionate
CAS Number: 5534-09-8
Other descriptive name: BDP
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: formoterol fumarate
CAS Number: 43229-80-7
Other descriptive name: FF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Trade Name: Foster 100/6 µg
Product Name: Foster 100/6 µg
Product Code: CHF 1535 HFA-134a
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: beclometasone dipropionate
CAS Number: 5534-09-8
Other descriptive name: BDP
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: formoterol fumarate
CAS Number: 43229-80-7
Other descriptive name: FF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Pressurised inhalation, solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): Change from baseline measured at clinic visit V2 (end of run-in) to the end of treatment period (V5) in pre-dose morning FEV1 (L) measured at clinic.

Main Objective: To demonstrate that CHF 1535 via NEXT™DPI (beclomethasone dipropionate + formoterol fumarate 100 + 6 µg), 1 inhalation or 2 inhalations twice daily, for 12 weeks is non-inferior to the corresponding dose of CHF 1535 via HFA-134a “extrafine” pMDI in terms of pulmonary function (change from baseline in pre-dose morning FEV1) in moderate to severe symptomatic asthmatic patients aged = 12 years under treatment with inhaled corticosteroids (< 2000 µg BDP or equivalent).

Secondary Objective: • To show that CHF 1535 via NEXT™ DPI and CHF 1535 via HFA-134a “extrafine” pMDI 2 inhalations twice daily are superior to the corresponding CHF 1535 via NEXT™ DPI and CHF 1535 via HFA-134a “extrafine” pMDI 1 inhalation twice daily in terms of pre dose morning FEV1.
• To evaluate the effect of the CHF 1535 via NEXT™ DPI compared to CHF 1535 via HFA-134a “extrafine” pMDI on other lung function parameters, on clinical outcome measures, on safety and tolerability

Secondary ID(s)

CCD-0705-PR-0027