E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease |
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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 |
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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 identify the optimal once-daily dose of CHF 4226 to be further developed for the treatment of patients with COPD |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of three different dosage strengths of CHF 4226 with salmeterol 50mcg b.i.d. and placebo, and to monitor for safety and tolerability. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Subgroup of 50 patients undergoing 24 hour Holter monitoring on Day -1 and Day 13.
2. Subgroup of 50 patients undergoing 24-hour spirometry testing on Day 14. |
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E.3 | Principal inclusion criteria |
Patients will be enrolled (at Visit 1) into the run-in period if they meet all the following criteria: − Patient has signed an IRB-/Ethics Committee-approved Informed Consent form; − Patient is a male or non-pregnant female > 40 and less than or equal to 75 years old; − Patient has a current or past smoking history > 15 pack-years; − Patient has a clinical diagnosis of COPD in accordance with the recommendations of the National Heart Lung and Blood Institute/World Health Organization (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD). − Patient meets the following requirements after an FEV1 albuterol reversibility test [i.e., 30 minutes following 200 mcg (metered dose) albuterol/salbutamol pMDI]: FEV1 is at least 0.9L 40% < FEV1 < 70% of patient’s predicted normal value ∆FEV1 > 4% of patient’s predicted normal value If ∆FEV1 ≤ 4% of patient’s predicted normal value, then this requirement must be met after retesting during the run-in period, at least 24 hours prior to Day -1. FEV1/FVC < 70% |
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E.4 | Principal exclusion criteria |
- Patient has a history of asthma, allergic rhinitis, or atopy; - Patient has a blood eosinophil count > 500/μL; - Patient had a COPD exacerbation or a lower respiratory tract infection within 8 weeks prior to screening, or during the run-in period, that resulted in the use of an antibiotic, or oral or parenteral corticosteroids; - Patient is on an inhaled corticosteroid that has been initiated, or the effective dose has been changed, within 4 weeks prior to screening or during the run-in period; - Patient has an uncontrolled cardiovascular (e.g., uncontrolled hypertension), respiratory, hematologic, immunologic, renal, neurologic, hepatic, endocrine (e.g., uncontrolled diabetes mellitus) or other disease, or any condition that might, in the judgment of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study; - Patient has a history of coronary artery disease, cerebrovascular disease, cardiac arrhythmias; - Patient has a concomitant disease of poor prognosis (e.g., cancer) - Patient has a serum potassium value ≤ 3.5 mEq/L or >5.5mEq/L and/or a fasting serum glucose value ≥ 140 mg/dL; - Patient has an abnormal QTc interval value in the Screening visit ECG test (i.e., > 450 msec in males or > 470 msec in females); - Patient has developed Cor Pulmonale; - Patient is receiving long term oxygen therapy, i.e., >16 hours/24-hour period, every day; - Patient has a known intolerance/hypersensitivity to β2-adrenergic agonists, propellant gases/excipients; - Patient is receiving treatment with a tricyclic antidepressant or a monoamine oxidase inhibitor (MAOI); - Patient has received a live-attenuated virus vaccination within two weeks prior to screening or during the run-in; - Patient is pregnant or lactating female, or female at risk of pregnancy (i.e., not using an adequate contraceptive method); - Patient is mentally or legally incapacitated; - Patient has participated in another investigational study within 30 days prior to screening; - Patient abuses alcohol or other substances; - Patient is potentially non-compliant or unable to perform required outcome measurements of the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from predose (mean of -1 hour and -10 minutes on Day 1) in trough (mean of 23 and 24 hrs) FEV1 (L) on Day 14, after 13 days of dosing |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |