A study to explore how the inhaled CHF 5993 (triple fixed combination) penetrates lungs using imaging technique

Phase 1

Conditions: COPD
MedDRA version: 20.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000015472
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2017-000438-79-HU

Lead Sponsor: Chiesi Farmaceutici S.p.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 30

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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 ß-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, ß2-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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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. ;Secondary Objective: 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.;<br> Primary end point(s): •Specific image-based airway volumes (siVaw): CT-based airway volumes normalized by the lung volume<br> •Specific image-based airway resistance (siRaw): CFD-based airway resistance normalized by the lung volume<br> ;Timepoint(s) of evaluation of this end point: during the trial

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: AEs, ADRs all across the study;<br> Secondary end point(s): • Internal Lobar Airflow Distribution<br> • Air Trapping<br> • Emphysema (Low Attenuation Score)<br> • Airway Wall Volume<br> • Blood Vessel Density<br> • Ventilation/Perfusion Matching<br> • Aerosol Deposition <br>

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