| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Obstructive Pulmonary Disease (COPD) |
|
| E.1.1.1 | Medical condition in easily understood language |
Breathing difficulties due to narrowing of the airways.
|
|
| 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 | PT |
| E.1.2 | Classification code | 10009033 |
| E.1.2 | Term | Chronic obstructive pulmonary disease |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| 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 is to identify the optimal dose of CHF 5259 glycopyrronium bromide (GB) to be further developed for the treatment of patients with COPD. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the effect of CHF 5259 glycopyrronium bromide (GB) on lung function parameters.
To assess the safety of the study treatments. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female patients aged ≥ 40 years at screening visit, who have signed an Informed
Consent form prior to initiation of any study-related procedure.
2. Patients with a diagnosis of COPD (according to GOLD guidelines 2015) at least 12
months before screening visit.
3. Current smoker or ex-smoker with a smoking history of at least 10 pack-years defined as
[(number of cigarettes smoked per day) × (number of years of smoking)] / 20.
(If the subjects undergo smoking cessation therapy, it must be completed 3 months prior to
the screening visit. Smoking cessation must be at least 3 months prior the screening. In both
cases the smoking status should not change between the subjects screening visit and subjects last study visit).
4. A post-bronchodilator FEV1 ≥ 40% and ≤70% of the predicted normal value (measured 30 to 45 minutes after administration of 80 μg ipratropium pMDI) and,
- a post-bronchodilator FEV1/FVC < 0.7 and,
- a change in FEV1 from the pre-bronchodilator value (reversibility) of at least 5% at
screening
If the criterion is not met at screening, the test can be rescheduled once before randomisation.
5. Patients under bronchodilators with long-acting muscarinic antagonist or long-acting
beta-2 agonist (monotherapy or dual therapy), or patients under ICS + LABA or ICS + LAMA for at least 4 weeks prior to screening. (Patients with a FEV1<50% of the predicted value and a history of 1 exacerbation whithin the last 12 months must have been treated with ICS+LABA or ICS+LAMA before screening)
6. Ability and cooperative attitude to understand and to perform required outcome measurements of the protocol (e.g. spirometry manoeuvres) and ability to understand the risks involved.
Ability to be trained to use the DPI inhalers. |
|
| E.4 | Principal exclusion criteria |
1. Diagnosis of asthma or other respiratory disorders (other than COPD) which may interfere
with data interpretation according to the investigator’s opinion.
2. Patients had a COPD exacerbation or a lower respiratory tract infection within 8 weeks prior to screening, or during the run-in period, that resulted in the use of an antibiotic, or oral or parenteral corticosteroids, or hospitalisation.
3. Patients with a history of ≥ 2 exacerbations within the last 12 months prior to screening
(frequent exacerbators).
4. Patients treated with oral/parenteral β2-agonists or nebulised bronchodilators or PDE
inhibitors or who received LABA/LAMA/ICS treatment therapy in the 4 weeks prior to
screening and during the run-in period.
5. Patient is on an inhaled corticosteroid that has been initiated, or the effective dose has been changed, within 4 weeks prior to screening or during the run-in period (patients on stable dose of ICS for at least 4 weeks prior to screening are allowed).
6. Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia.
7. Patients with known respiratory disorders other than COPD.
8. Patients with medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic.
9. Patients who have unstable concurrent 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;
10. Patients who have a concomitant disease of poor prognosis
11. Patients who have clinically significant cardiovascular condition
12. Patients with known atrial fibrillation (AF):
a. Paroxysmal Atrial Fibrillation
b. Persistent: AF episode lasting more than 7 days or requiring termination by
cardioversion, either with drugs or by direct current cardioversion (DCC) within 6 months prior to screening visit.
c. Long standing persistent: continuous atrial fibrillation diagnosed for less than 6 months
and/ or without a rhythm control strategy.
d. Permanent: AF diagnosed for at least 6 months with a resting ventricular rate ≥ 100/min
not controlled with a rate control strategy (i.e., selective β-blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy).
13. Patients have a clinically significant abnormal 12-lead ECG that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.
14. Patients whose electrocardiogram 12-lead ECG shows a QTcF>450 ms for males or QTcF > 470 ms for females.
15. Patients with 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.
16. Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they are willing to use a highly effective birth control methods such as :
a. Placement of an intrauterine device or intrauterine releasing system
b. Oral, intravaginal, transdermal combined estrogen and progestogen containing hormonal contraception or oral, injectable, implantable progestogen only hormonal
contraception.
c. Bilateral tubal occlusion
d. Partner vasectomy (provided that partner is the sole sexual partner of the WOCBP
trial participant and that the vasectomised partner has received medical assessment of
the surgical success)
e. sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments
Female patients of non-childbearing potential defined as physiologically incapable of
becoming pregnant: post-menopausal ( defined as no menses for 12 months without an
alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) are eligible.
17. Patients known to have intolerance/hypersensitivity or any contra-indication to treatment with M3 Antagonist or any of the excipients contained in the formulations used in the study.
18. Patients who have evidence of alcohol or drug abuse, not compliant with the study protocol or not compliant with the study treatments according to investigator’s judgment.
19. Patients with major surgery in the previous 3 months or planned during the trial which may affect patient’s compliance in study procedures.
20. Patients who have participated in another clinical trial with an investigational drug in the 2 months preceding the screening.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| FEV1 AUC 0-12h normalised by time |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
EFFICACY VARIABLES:
FEV1, FVC, Transition Dyspnoea Index (TDI)
SAFETY VARIABLES:
Adverse events and adverse drug reactions
Vital signs, ECG and laboratory |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Day 1, day 14 and/or day 28, and across the study for safety variables |
|
| 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) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| incomplete block, 3-way crossover |
|
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 10 |
| 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
|
|
| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 2 |
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