E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic obstructive pulmonary disease (COPD) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic obstructive pulmonary disease (COPD) |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 100000004855 |
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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 efficacy of CHF 5993 to improve pre-dose lung function (pre-dose morning FEV1) compared with CHF 1535 |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the efficacy of CHF 5993 to improve post-dose lung function (2-hour post dose FEV1) compared with CHF 1535 To demonstrate the efficacy of CHF 5993 to reduce the annual rate of moderate and severe COPD exacerbations compared with CHF 1535 To demonstrate the efficacy of CHF 5993 to improve health-related quality of life (decrease from baseline in total SGRQ score =4) compared with CHF 1535 To assess the long-term safety and tolerability of CHF 5993 compared with CHF 1535 To evaluate the effect of CHF 5993 on other lung function parameters, subject’s health status and clinical outcome measures compared with CHF 1535 |
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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 |
Population Pharmacokinetic parameters for Beclomethasone 17-Monopropionate (B17MP), Glycopyrronium bromide (GB) and formoterol, as applicable, from subset of subjects undergoing blood collection at Week 0 (V2), Week 28 (V7) and Week 52(V11).
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E.3 | Principal inclusion criteria |
1. A signed and dated written informed consent must be obtained prior to initiating any study related procedures 2. Outpatient population 3. Male or female subjects aged >40 years 4. For Woman of Childbearing Potential with fertile / non-fertile male partners and for Female subjects of nonchildbearing potential see protocol, criteria 4. 5. COPD diagnosis for at least 12 months before the screening visit in accordance with the definition by the GOLD 2020 Report 6. Current or ex-smokers who quit smoking at least 6 months prior to screening with a smoking history of at least 10 pack-years 7. Symptomatic subjects based on COPD Assessment Test (CAT) score ≥10 8. A pre- and post-bronchodilator FEV1/FVC ratio <0.70 at screening 9. A post-bronchodilator FEV1 <50% predicted normal at screening and a documented history of ≥1 moderate or severe COPD exacerbation in the previous 12 months OR a post-bronchodilator FEV1 ≥50% and <80% of predicted normal at screening and a documented history of ≥2 moderate COPD exacerbations or ≥1 severe COPD exacerbation in the previous 12 months Global Lung Function Initiative reference equations will be used to calculate percent predicted values (for COPD exacerbation details see study protocol). 10. Subjects receiving daily inhaled maintenance therapy for their COPD, at a stable dose for at least 3 months prior to the screening and randomization visits 11. Documentation (including imagery and report) of chest x-ray (CXR) or CT scan performed within 6 months prior to the screening visit, without evidence of significant abnormalities (other than those related to the presence of COPD). 12. A cooperative attitude and ability to demonstrate correct use of the pMDI inhalers and eDiary.
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E.4 | Principal exclusion criteria |
1. Female subjects who are pregnant (as evident by a positive urine hCG or serum β-hCG test) or lactating 2. Subjects using the following medications prior to the screening visit and during the run-in period: a. Systemic/oral/parenteral corticosteroids in the prior 4 weeks b. Use of antibiotics for a lower respiratory tract infection (e.g. pneumonia) or COPD exacerbation in the prior 4 weeks c. Any long-term chronic maintenance use of antibiotic treatment in the prior 4 weeks d. Oral xanthine derivatives (e.g. theophylline) in the prior 7 days 3. A moderate or severe COPD exacerbation or a lower respiratory tract infection (e.g., pneumonia) that has not resolved ≤14 days prior to the screening visit or during the run-in period 4. Subjects being treated with non-cardioselective β-blockers 5. Subjects requiring long term (> 15 hours daily) oxygen therapy 6. Known respiratory disorders other than COPD which may impact the efficacy of the study drug according to investigator’s judgement. 7. Lung transplant surgery or lung volume reduction surgery 8. 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 9. History of hypersensitivity to M3 receptor antagonists, β2 agonists, corticosteroids or any of the excipients contained in any of the study drugs used in the trial which may raise contraindications or impact the efficacy of the study drug according to the investigator’s judgement 10. Subject has severe, acute or uncontrolled cardiovascular condition (such as but not limited to unstable ischemic heart disease, NYHA Class IV, left ventricular failure, acute myocardial infarction or unstable angina) in the last 6 months 11. An abnormal and clinically significant 12-lead ECG at either the screening or randomization visit. 12. 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 13. Unstable or uncontrolled concurrent disease which may impact the efficacy or safety of the study drug or the subject’s participation in the study according to investigator’s judgment 14. Malignancy that has not been in complete remission for at least 1 year or any untreated (e.g. resected for cure) localized carcinomas For complete list of exclusion criteria see protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in pre-dose morning FEV1 at week 28 (V7)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization (V2) till week 28 (V7) |
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E.5.2 | Secondary end point(s) |
Efficacy: 1.Change from baseline in 2-hour post-dose morning FEV1 at week 28 (V7) 2.Rate of moderate and severe COPD exacerbations over 52 weeks of treatment 3.SGRQ response (Decrease from baseline in total score =4 at Week 28
Safety: 1.Incidence of treatment-emergent adverse events (TEAEs), adverse drug reactions (ADRs), serious ADRs, serious AEs (SAEs), severe AEs, TEAEs leading to discontinuation from study drug, and TEAEs leading to death 2.Incidence of treatment-emergent pneumonia 3. Incidence of treatment-emergent major adverse cardiovascular events (MACE).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy 1. and 3.From randomization (V2) till week 28 (V7) 2.From randomization (V2) till week 52 (V11)
Safety: 1-3.From randomization (V2) till week 53 (V12) |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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.8.2.4 | 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 | 28 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 779 |
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 |
Argentina |
Ukraine |
Bulgaria |
Czechia |
Hungary |
Mexico |
Poland |
Russian Federation |
United States |
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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
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The last visit of the last subject in 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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |