E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease |
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E.1.1.1 | Medical condition in easily understood language |
Difficulty breathing as a result of the narrowing of airways (Obstruction of airflow) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 demonstrate the non-inferiority of CHF 5993 pMDI versus fixed combination of fluticasone furoate/vilanterol plus tiotropium in terms of quality of life (change from baseline in the St. George’s Respiratory Questionnaire [SGRQ] total score after 26 weeks of treatment). |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of CHF 5993 pMDI on lung function parameters, patient’s health status and on clinical outcome measures.
• To collect data in order to assess the impact of study treatments on health economic outcomes.
• To assess the safety and tolerability of the study treatments.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female adults aged ≥ 40 years with written informed consent obtained prior to any study-related procedure.
2. Patients with a diagnosis of COPD at least 12 months before the screening visit (according to GOLD document updated 2014).
3. Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years
4. A post-bronchodilator FEV1 < 50% of the predicted normal value and a post-bronchodilator FEV1/FVC < 0.7 at least 10-15 min after 4 puffs (4 x 100 µg) of salbutamol pMDI.
5. A documented history of at least one exacerbation in the 12 months preceding the screening visit.
6. Patients under double therapy for at least 2 months prior to screening visit of an inhaled corticosteriod (ICS) plus a long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist (LABA) or a double combination of LABA/LAMA
7. Symptomatic patients at screening with a CAT score ≥10.
8. A cooperative attitude and ability to use correctly the inhalers.
9. A cooperative attitude and ability to use correctly the daily eDiary. |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS are willing to use one or more methods of contraception as defined in the protocol
2. Patients with a current clinical diagnosis of asthma with a physician-judged need for inhaled or oral corticosteroid therapy
3. Patients requiring use of systemic steroids, antibiotics, PDE4 inhibitors in the 4 weeks prior to screening
4. COPD exacerbation requiring prescriptions of systemic corticosteroids and/or antibiotics or hospitalization during the run-in period
5. Patients treated with non-cardio selective β-blockers for at least 10 days before randomization
6. Patients treated with long-acting antihistamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study, or if taken as PRN.
7. Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia.
8. Known respiratory disorders other than COPD which may impact the efficacy of the study drug according the investigator’s judgment
9. Patients who have clinically significant cardiovascular condition
10. Patients with atrial fibrillation (AF)
11. An abnormal and clinically significant 12-lead ECG which may impact the safety of the patient according to investigator’s judgement
12. Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic agents
13. History of hypersensitivity to anticholinergics, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial which may raise contra-indications or impact the efficacy of the study drug according to the investigator’s judgement
14. Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug according to investigator’s judgement
15. Patients with hypokalaemia or uncontrolled hyperkalaemia according to investigator’s judgment
16. Unstable concurrent disease which may impact the efficacy or the safety of the study drug according to investigator’s judgment.
17. Patients with any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next six months (after V1) or with malignancy for which they are currently undergoing radiation therapy or chemotherapy
18. History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit
19. Participation in another clinical trial where investigation drug was received less than 8 weeks prior to screening visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the SGRQ total score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 2 (week 0) to visit 5 (week 26) |
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E.5.2 | Secondary end point(s) |
• SGRQ response (change from baseline in total score ≤ -4)
• Change from baseline in the SGRQ total score
• Change from baseline in pre-dose morning FEV1, FVC and FEV1 response
• Change from baseline of night-time COPD symptoms on sleep
• Use of rescue medication
• CAT score at the end of treatment
• Rate of moderate and severe COPD exacerbation over 26 weeks of treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 | No |
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 |
Belgium |
Germany |
Hungary |
Lithuania |
Netherlands |
Poland |
Romania |
Russian Federation |
South Africa |
Sweden |
Turkey |
United Kingdom |
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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
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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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |