E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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 evaluate the superiority of CHF 5259 pMDI (glycopyrrolate bromide) (50 μg total daily dose) versus placebo in terms of FEV1 AUC0-12h normalised by time on Day 42.
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E.2.2 | Secondary objectives of the trial |
Key Secondary objective
To evaluate the superiority of CHF 5259 pMDI (50 μg total daily dose) versus placebo in terms of peak FEV1 on Day 42.
Secondary objectives
To evaluate the effect of CHF 5259 on other lung function parameters and on clinical outcome measures.
To assess the safety and tolerability of study treatments. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient’s written informed consent obtained prior to any study-related procedures
2. Male or female patients aged ≥18 and ≤75 years.
3. History of asthma ≥ 5-year and diagnosed before the age of 40 years.
4. Patients with uncontrolled asthma on low-medium doses of Inhaled Corticosteroid (ICS) (200 – 1000 μg daily dose BDP non-extrafine or estimated clinical comparable dose) at a stable dose for at least 4 weeks prior to screening.
5. Patients with a pre-bronchodilator FEV1 ≥40% and <90% of their predicted normal value, after appropriate washout from bronchodilators, at screening and at the end of the run-in period.
6. Patients with a positive response to the reversibility test at screening within 30 minutes after administration of 400 μg of salbutamol pMDI, defined as ΔFEV1 ≥ 12% and ≥ 200mL over baseline.
7. Patients with uncontrolled asthma evidenced by a score at the Asthma Control Questionnaire© (ACQ) ≥1.5 (criterion must be met at screening and at the end of the run-in period).
8. Patients with a co-operative attitude and ability to be trained to correctly use the pMDI and the electronic peakflow meter. |
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E.4 | Principal exclusion criteria |
1. Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake.
2. History of near fatal asthma or of a past hospitalisation for asthma in intensive care unit or of frequent exacerbations in the last year which may place the patient at risk.
3. Hospitalisation, emergency room admission or use of systemic corticosteroids for asthma exacerbation in the 4 weeks prior to screening visit or during the run-in period.
4. Lower respiratory tract infection in the 4 weeks before the screening visit or during the run-in period.
5. Patients who are in current therapy for gastroesophageal reflux disease (GERD) or patients with a medical history of GERD that leads to asthma symptoms.
6. Patients with a seasonal worsening of asthma and who cannot complete the study outside the relevant allergen season.
7. History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, bronco-carcinoma, lung carcinoma or any other significant lung disease which may interfere with data evaluation.
8. Patients with a medical history or current diagnosis of COPD as defined by the GOLD guidelines (2014).
9. Current smokers or ex-smokers with total cumulative exposure equal or more than 10 pack-years or having stopped smoking one year or less prior to screening visit.
10. Any change in dose, schedule or formulation of ICS in the 4 weeks prior to screening visit.
11. Patient had used any of the following treatments 4 weeks before screening visit: inhaled long-acting β2-agonists (LABAs), inhaled long acting muscarinic antagonists (LAMAs), inhaled ICS/LABA fixed combinations, theophylline, leukotriene modifiers, cromolyn sodium, nedocromil sodium, systemic anticholinergics, systemic corticosteroids (12 weeks for slow release corticosteroids).
12. Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS are using at least one or more reliable methods of contraception.
13. Patients who received any investigational new drug or participated in clinical study either within the last 8 weeks (or 5 half-lives for biologic products with slow elimination) before screening.
14. Patients who have clinically significant cardiovascular condition according to investigator’s judgement
15. An abnormal and clinically significant 12-lead ECG that results in active medical problem which may impact the safety of the patient according to investigator’s judgement
16. Patients whose electrocardiogram (12-lead ECG) shows QTcF >450 ms for males or QTcF >470 ms for females at screening or at randomisation visits.
17. Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator, would prevent use of anticholinergic agents.
18. Unstable concurrent disease
19. Patients having received a live-attenuated virus vaccination within
two weeks prior to screening or during the run-in phase
20. Patients mentally or legally incapacitated.
21. Patients with a history of alcohol or drug abuse.
22. Patients with known intolerance/hypersensitivity or contra-indication to treatment with ß2-agonists, inhaled corticosteroids, anti-cholinergics or propellant gases/excipients.
23. Patients with major surgery in the 3 months prior to screening visit or planned surgery during the trial.
24. Patients being treated with anti-IgE antibodies.
25. Patients treated with non-potassium sparing diuretics , non-selective beta-blocking drugs quinidine, quinidine-like anti arrhythmics, or any medication with a QTc prolongation potential or a history of QTc prolongation.
26. Patients treated with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants.
27. Patients who are receiving any therapy that could interfere with the study drugs according to investigator’s opinion. |
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E.5 End points |
E.5.1 | Primary end point(s) |
FEV1 AUC0-12h normalised by time on Day 42 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from baseline in peak FEV1 .
Safety (Adverse Events and Adverse Drug Reactions)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 42
(across the study for the safety) |
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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 | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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A follow-up call, 1 week after the visit 5 |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |