| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic obstructive pulmonary disease (COPD) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10009033 |
| E.1.2 | Term | Chronic obstructive pulmonary disease |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate that CHF 1535 twice daily is superior to Formoterol alone twice daily in terms of number of COPD exacerbations during 48 weeks of treatment and non-inferior to Budesonide plus Formoterol twice daily in terms of pulmonary function (change in pre-dose morning FEV1 from baseline to 48 weeks) in patients with stable severe COPD. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the efficacy of the test treatment in terms of health related quality of life (HRQL), COPD symptoms, other pulmonary function parameters (FVC, PEF, FEF25-75%), use of “rescue” medication, number of moderate and severe COPD exacerbations, time to first moderate and severe COPD exacerbation, dyspnoea index, BODE index, and to evaluate the safety profile through adverse events (AEs) and adverse drug reactions (ADRs) reporting, electrocardiography, blood chemistry (serum potassium, serum cortisol and plasma glucose levels), vital signs. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Written informed consent obtained
2. Male and female outpatients, aged ≥ 40 years
3. Patients with a clinical diagnosis of COPD (according to GOLD guidelines)
4. FEV1 ≥ 30% and < 50% of the predicted normal values post-bronchodilator (and at least 0.7 L absolute value)
5. FEV1/FVC ratio ≤ 70%
6. COPD symptoms for at least 2 years
7. At least 1 exacerbation requiring medical intervention (oral corticosteroid and/or antibiotic treatment and/or need for a visit to an emergency department and/or hospitalization) within 2-12 months before the screening visit
8. Current or previous smoker (in both cases with a cumulative exposure to cigarette smoke of more than 20 pack-years)
9. A cooperative attitude and ability to be trained to use correctly the pMDI and the DPI inhalers.
|
|
| E.4 | Principal exclusion criteria |
1. Female subjects: pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (i.e. contraceptive methods other than oral contraceptives, IUD, tubal ligature)
2. Current or past diagnosis of asthma
3. History of allergic rhinitis or other atopic disease (e.g. eczema)
4. Onset of obstructive symptoms early in life (for example childhood)
5. Variability of symptoms from day to day and frequent symptoms at night and early morning (suggestive of asthma)
6. Positive FEV1 reversibility test: ∆FEV1 30 minutes following inhalation of 200 µg of salbutamol pMDI more than 12% of predicted normal value [FEV1 change (L)/FEV1 predicted normal value (L) x 100]
7. A total blood eosinophil count higher than 500/µL
8. Clinically significant or unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; significant pulmonary disease (e.g. tuberculosis, lung cancer or other); cardiovascular disease (e.g. coronary artery disease, uncontrolled hypertension); gastrointestinal disease (e.g. active peptic ulcer); neurological disease; haematological disease; autoimmune disorders, or other
9. Evidence of heart failure (NYHA class III-IV)
10. Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease.
11. Patients with serum potassium levels ≤ 3.5 mEq/L (or 3.5 mmol/L)
12. Patient with narrow-angle glaucoma
13. QTc interval (Bazett’s formula) higher than 450 msec at screening visit (Visit 1)
14. Lower respiratory tract infection within two months before screening visit (Visit 1) and during the run-in period of the study
15. Hospitalisation or emergency room treatment for an acute COPD exacerbation in the two months before screening visit (Visit 1) and during the run-in period of the study
16. Long term oxygen therapy
17. Patients treated with oral or injectable corticosteroids and antibiotics for a COPD exacerbation and/or a lower respiratory tract infection in the two months preceding the screening visit (Visit 1) and during the run-in period of the study
18. Patients treated with depot corticosteroids in the two months preceding the screening visit (Visit 1) and during the run-in period of the study
19. Changes in dose, schedule, formulation or product of a nasal corticosteroid or an oral modified-release theophylline within two months of screening visit (Visit 1) and during the run-in period of the study
20. Patients treated with long-acting antihistamines (e.g. astemizole, terfenadine) in the two months preceding the screening visit (Visit 1) and during the 52-week study period.
21. Patients treated with beta-blockers in the week preceding the screening visit (Visit 1) and during the 52-week study period
22. Patients with allergy, sensitivity or intolerance to sympathomimetic drugs or corticosteroids or to any of the excipients contained in the study drugs
23. Patients who have evidence of alcohol or drug abuse, not compliant with the study protocol or not compliant with the study treatments
24. Participation in another clinical trial with an investigational drug in the four weeks preceding the screening visit (Visit 1)
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
· Number of COPD exacerbation
· Change in pre-dose morning FEV1 from baseline to 48 weeks.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 59 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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