| 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) |
|
| 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 | 19.0 |
| 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 |
| The primary objective of this trial will be to investigate the dose-response relationship of 4 doses of CHF 6001 DPI with respect to predose FEV1 after 12 weeks of treatment and to identify the optimal dose of CHF 6001 for further development in the target patient population. |
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| E.2.2 | Secondary objectives of the trial |
- To assess the efficacy of the different doses of CHF 6001 DPI in comparison with placebo on other lung function parameters (pre-dose FVC, IC), on symptoms benefit (TDI, SGRQ score, E-RS scores, rescue use) and on exacerbations reduction after 24 weeks of treatment;
- To evaluate the effect of CHF 6001 in comparison with ICS;
- To monitor for safety and tolerability. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Male and female aged ≥40 years with written informed consent.
2.A female is eligible to enter the study if she is of non- childbearing potential i.e. physiologically incapable of becoming pregnant or woman permanently sterilized
3.With an established diagnosis of COPD (according to GOLD guidelines, revised 2015(1)) at least 12 months prior to the screening visit.
4.With a smoking history of at least 10 pack years [pack-years = (number of cigarettes per day x number of years)/20]. Current and ex-smokers are eligible.
5.With a post-bronchodilator FEV1 >/=30% and </=70% of the patient predicted normal value and a post-bronchodilator FEV1/FVC ratio <0.7 measured 10 to 15 min after administration of 400µg (4 puffs x 100µg) of salbutamol pMDI.
6.With a documented history (e.g. medical record verification) of at least 1 moderate or severe exacerbation in the 12 months prior to study entry.
7.Patients must be symptomatic at screening defined as having a MMRC score ≥2 and a CAT score ≥10.
8.Patients must be receiving daily maintenance therapy with an ICS/LABA only, at stable dose and dosage regimen, for at least 2 months prior to screening.
9.Patients must have a cooperative attitude and ability to be trained to use correctly the DPI inhalers.
10.Patients must have a cooperative attitude and ability to be trained to use correctly the electronic devices with COPD questionnaire, to understand and to perform required outcome measurements of the protocol (e.g. spirometry manoeuvres, ) and ability to understand the risks involved.
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|
| E.4 | Principal exclusion criteria |
1. A diagnosis of asthma or other respiratory disorders (other than COPD) which may interfere with data interpretation
2.On maintenance bronchodilators therapy only (LABA alone, LAMA alone, dual LABA/LAMA) within 8 weeks prior to screening.
3.On maintenance triple therapy (ICS/LABA plus LAMA), or LAMA plus ICS combination therapy, or on PDE4 inhibitors (e.g. roflumilast) within 8 weeks prior to screening.
4.Moderate or severe COPD exacerbation or a lower respiratory tract infection within 6 weeks prior to study entry or during the run-in period.
5.Requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia.
6.Participating to a pulmonary rehabilitation programme or completing such a programme within the last 6 weeks prior to screening.
7.Known respiratory disorders other than COPD that in the investigator’s opinion would affect efficacy and safety evaluation or place the patient at risk.
8.Lung cancer or a history of lung cancer.
9.Active cancer or a history of cancer with less than 5 years disease free survival time. Localized carcinoma is acceptable.
10.A history of hypersensitivity to β2-agonist, corticosteroids, PDE4 inhibitors or any of the excipients contained in any of the formulations used in the trial.
11.Diagnosis of depression, generalised anxiety disorder, suicidal ideation or behaviour that might, according to the investigator judgement, place the patient at undue risk.
12.Clinically significant cardiovascular condition such as, but not limited to, unstable ischemic heart disease, NYHA Class III/IV heart failure, acute ischemic heart disease within one year prior to study entry, known history of atrial fibrillation or history of sustained and non-sustained cardiac arrhythmias diagnosed within the last 6 months prior to study entry, not controlled with a rate control strategy.
13.Clinically significant abnormal 12-lead ECG that, in the investigator’s opinion, would affect efficacy or safety evaluation or place the patient at risk.
14.Serum potassium value ≤3.5 mEq/L or >5.5mEq/L and/or a fasting serum glucose value ≥ 140 mg/dL.
15.History or symptoms of significant neurological disease including transient ischemic attack (TIA), stroke, seizure disorder or behavioural disturbances.
16.Unstable concurrent disease or other disease or condition that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.
17.Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.
18.Abnormal ALT ≥2x upper limit of normal (ULN) and/ or AST ≥2x ULN and/or bilirubin ≥1.5x ULN. Isolated bilirubin ≥1.5x ULN is acceptable if fractionated and direct bilirubin is <35%.
19.Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
20.Receiving treatment with any drug known to have a well defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole) within the previous 3 months before the screening visit.
21.Severely obese (BMI ≥35 kg/m2) or have experienced excessive weight loss recently.
22.History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit.
23.Received any other investigational drug within the preceding 30 days (60 days for biologics), or a longer and more appropriate time as determined by the Investigator |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary efficacy variable
•Change from baseline in morning predose FEV1 at week 12.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary efficacy variables
•Change from baseline in morning predose FEV1.
•Change from baseline in morning predose morning FVC and IC.
•TDI score at all visits and proportion of patients with a TDI ≥1 unit
•Change from baseline to all visits in SGRQ total score and domain scores and proportion of patients with a change from baseline in SGRQ score ≥ -4 units.
•Moderate and severe COPD exacerbation rate over 24 weeks of treatment.
Time to first moderate or severe COPD exacerbation. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| 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 | 17 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 82 |
| 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 |
| Bulgaria |
| Germany |
| Hungary |
| Poland |
| Romania |
| Russian Federation |
| Ukraine |
| United Kingdom |
|
| 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
|
|
| 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 | 4 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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