| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Severe Chronic Obstructive Pulmonary Disease (COPD) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010952 |
| E.1.2 | Term | COPD |
|
| 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
twice daily in terms of COPD exacerbations rate after 48 weeks of
treatment and in terms of pulmonary function (change in pre-dose
morning FEV1 from baseline to 12 weeks) in patients with severe
COPD. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the efficacy of CHF 1535 in terms of pulmonary function
parameters (change in pre-dose morning FEV1 from baseline to 12
weeks within treatment groups, change in pre-dose morning FEV1
from baseline to 48 weeks, morning pre-dose FEV1 and pre-dose
FVC at all clinic visits , pre-dose FEV1 over the treatment period
(average), post-dose 2-hour FEV1), time to first COPD exacerbation,
patient’s health status assessed by St. George’s Respiratory
Questionnaire (SGRQ), use of rescue medication and to evaluate the
safety profile in terms of adverse events (AEs), adverse drug
reactions (ADRs), blood haematology/chemistry and vital signs. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male and female adults aged > 40 years, who have signed an
Informed Consent form prior to initiation of any study-related
procedure or written informed consent obtained by legal
representative (when applicable).
2. Outpatients with severe COPD (stage III from GOLD guidelines
2008), characterized by shortness of breath, reduced exercise
capacity, fatigue, and repeated exacerbations that almost always
have an impact on patients’ quality of life and including:
a) Smoking history of at least 10 pack years, both current and
ex-smokers are eligible. Ex-smokers will be defined as
subjects who quit smoking at least six months prior to
screening.
b) Post-bronchodilator 30% ≤ FEV1 < 50% of the predicted
normal value.
c) Post-bronchodilator FEV1/FVC < 0.7.
3. A documented (e.g. patient’s records at the admitting hospital)
history of at least one exacerbation in the previous 12 months.
COPD exacerbation will be defined according to the following:
“A sustained worsening of the patient’s condition (dyspnoea,
cough and/or sputum production/purulence), from the stable state
and beyond normal day-to-day variations, that is acute in onset
and necessitates a change in regular medication in a patient with
underlying COPD that includes prescriptions of systemic
corticosteroids and/or antibiotics, or need for a visit to an
emergency department or hospitalization”
4. A cooperative attitude and ability to be trained to use correctly
the pMDI inhalers.
5. A cooperative attitude and ability to be trained to recognize
worsening symptoms of COPD and record variations correctly in
the digital platform (BlackBerry®) pre-loaded with the EXACTPRO
questionnaire. |
|
| E.4 | Principal exclusion criteria |
1. Pregnant or lactating women. Females of childbearing potential
without an efficient contraception 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 are using
one or more of the following acceptable methods of
contraception:
a) surgical sterilization (e.g., bilateral tubal ligation,
hysterectomy);
b) hormonal contraception (implantable, patch, oral,
injectable);
c) double-barrier methods (any double combination of: IUD,
male or female condom, diaphragm, sponge, cervical cap).Acceptable methods of contraception may include total
abstinence at the discretion of the investigator in cases where the
age, career, lifestyle, or sexual orientation of the patient ensures
compliance. 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.
2. 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. Unstable concurrent disease: e.g. uncontrolled
hyperthyroidism, uncontrolled diabetes mellitus or other
endocrine disease; significant hepatic impairment; significant
renal impairment; significant non COPD pulmonary disease (e.g.
tuberculosis, lung cancer or other); cardiovascular disease (e.g.
uncontrolled coronary artery disease, uncontrolled hypertension);
uncontrolled gastrointestinal disease (e.g. active peptic ulcer);
neurological disease; uncontrolled haematological disease;
uncontrolled autoimmune disorders, or other which may impact
the feasibility of the results of the study according to
investigator’s judgement.
6. Evidence of heart failure (NYHA class IV).
7. Clinically significant laboratory abnormalities indicating a
significant or unstable concomitant disease which may impact
the feasibility of the results of the study according to
investigator’s judgement.
8. Patients with serum potassium levels < 3.5 mEq/L (or 3.5
mmol/L).
9. Patient with narrow-angle glaucoma.
10. Patients with COPD exacerbations requiring oral steroids in
the 4 weeks prior to screening and during the 2 week run-in.
11. Patients requiring long term (at least 12 hours daily) oxygen
therapy for chronic hypoxemia.
12. Patients treated with depot corticosteroids in the two months
preceding the screening visit (Visit 1) and during the run-in
period of the study.
13. Changes in dose, schedule, formulation or product of
tiotropium within three months before screening visit (Visit 1)
and during the run-in period.
14. Changes in dose, schedule, formulation or product of oral
theophylline within two months of screening visit (Visit 1) and
during the run-in period of the study.
15. Patients treated with long-acting antihistamines (e.g.
astemizole, terfenadine) in the two months preceding the
screening visit (Visit 1) and during the 50 week study period.16. Patients treated with beta-blockers in the week preceding the
screening visit (Visit 1) and during the 50 week study period.
17. Patients with allergy, sensitivity or intolerance to
sympathomimetic drugs or corticosteroids or to any of the
excipients contained in the study drugs.
18. Patients who have evidence of alcohol or drug abuse, not
compliant with the study protocol or not compliant with the
study treatments according to investigator’s judgement.
19. Participation in another clinical trial with an investigational
drug in the four weeks preceding the screening visit (Visit 1).
20. Patients requiring chronic mechanical ventilation for COPD. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Co-Primary Endpoints
Lung functions based endpoint:
Superiority of CHF 1535 versus Formoterol in terms of change in
pre-dose morning FEV1 from baseline to 12 weeks
Symptoms based endpoint:
Superiority of CHF 1535 versus Formoterol in terms of COPD
exacerbations rate |
|
| 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 | Yes |
| 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 | No |
| 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 | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 37 |
| 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 | Yes |
| 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 | 2 |
| 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 | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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