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 |
difficulty in breathing due to chronic airway obstruction |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 100000015472 |
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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 effect of inhaled extrafine CHF5993 pMDI on airway volumes, and resistance, by Functional Respiratory Imaging (FRI), in COPD patients treated with a non extrafine extemporary triple combination for three months, before entering the study. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of inhaled extrafine CHF5993 pMDI on lung function parameters, on disease symptoms and Quality of Life, additional CFD based parameters, and aerosol deposition. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject’s written informed consent obtained prior to any study-related procedure.
2. Male or Female COPD patients aged ≥ 40 years.
3. Smoking history: of at least 10 pack-years
4. Smoking status: current or ex-smokers. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to screening visit.
If the subjects undergo smoking cessation therapy, it must be completed 3 months prior to study entry.
5. Patients with documented COPD at least 12 months according to GOLD 2017.
6. Post-bronchodilator (BD) decreased Tiffeneau index: FEV1/FVC < 0.70.
7. Patients who present post- BD FEV1 less than 50 % of predicted.
8. Patients who present (Functional residual capacity) FRC ≥120% predicted.
9. Patients who present CAT assessment ≥10.
10. Patients on stable respiratory medications for at least 3 months prior to screening with non extrafine extemporary triple combination.
11. Body Mass Index (BMI) between 18.0 and 32.0 kg/m2 (extremes included) at the screening visit.
12. Ability to understand the study procedures and the risks involved and ability to be trained with DPI and pMDI training inhalers to use the devices correctly.
13. WOCBP fulfilling one of the following criteria:
a. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up visit or
b. WOCBP with non-fertile male partners (contraception is not required in this case).
14. Female patients of non-childbearing potential defined as physiologically incapable of becoming pregnant |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating women.
2. Patients with history or current diagnosis of asthma.
3. Medical history or current diagnosis of allergic rhinitis or atopy
4. Patients requiring use of the following medications:
a. Systemic steroids for COPD exacerbation in the 4 weeks
prior to screening;
b. Patients with a moderate or severe COPD exacerbation [i.e. resulting in the use of systemic corticosteroids (oral/IV/IM) and or antibiotics or need for hospitalization
within 6 weeks prior to screening]
c. A course of antibiotics for COPD exacerbation longer
than 7 days in the 4 weeks prior to screening;
d. c-Phosphodiesterase-4 (PDE-4) inhibitors in the 4 weeks
prior to screening;
e. Use of antibiotics for a lower respiratory tract infection
(e.g. pneumonia) in the 4 weeks prior to screening;
5. Patients treated with non-cardio-selective β-blockers in the week
prior screening.
6. Patients treated with long-acting anti-histamines unless taken at
stable regimen at least 2 months prior to screening and to be
maintained constant during the study.
7. Patients requiring long term (at least 12 hours daily) oxygen therapy
for chronic hypoxemia.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 treatment according the Investigator’s judgment.
9.Lung cancer or history of lung cancer
10.Lung resection: subjects with a history of lung volume resection.
11.Subjects who have cardiovascular condition such as, but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, acute ischemic heart disease in the last year prior to study screening, which may impact the safety of the subject or the evaluation of the result of the study according to the Investigator’s judgment
12.ECG criteria: any clinically significant abnormal 12-lead ECG that in the investigator's opinion would affect efficacy or safety evaluation or place the patients at risk.
13.Medical history or current diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that in the opinion of the Investigator would have prevented use of anticholinergic agents.
14.History of hypersensitivity to M3 antagonists, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the study which may raise contra-indications or impacted the efficacy of the study treatment according to the Investigator’s judgment.
15.Clinical Significant laboratory abnormalities indicating a significant or unstable concomitant disease which may have impacted the efficacy or the safety of the study treatment according to Investigator’s judgment.
16.Patients with serum potassium levels < 3.5 mEq/L (or 3.5 mmol/L).
17.Unstable concurrent disease which may impact the feasibility of the results of the study according to Investigator’s judgment.
18.History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening.
19.Drugs with hepatoxic potential within the previous 3 months before the screening visit.
20. Changes in dose, schedule, formulation or product of oral xanthine derivatives (e.g. Theophylline) in the month prior screening visit.
21.Participation to investigational trial: patients who have received any investigational drug within the 30 days ( 60 days for biologics) before the screening visit
22.Treatment with strong CYP3A inhibitors ( within 4 weeks prior to study entry.
23. Serology at the screening positive to HIV1 or HIV2 and positive results for Hepatitis which indicates acute or chronic Hepatitis B or Hepatitis C
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E.5 End points |
E.5.1 | Primary end point(s) |
•Specific image-based airway volumes (siVaw): CT-based airway volumes normalized by the lung volume
•Specific image-based airway resistance (siRaw): CFD-based airway resistance normalized by the lung volume
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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) |
• Internal Lobar Airflow Distribution
• Air Trapping
• Emphysema (Low Attenuation Score)
• Airway Wall Volume
• Blood Vessel Density
• Ventilation/Perfusion Matching
• Aerosol Deposition
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
AEs, ADRs all across the study |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
airway exploration by FRI |
|
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
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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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 | |
E.8.9.1 | In the Member State concerned days | |