| 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 |
| obstructive lung disease characterized by long-term breathing problems and poor airflow |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| 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 compare the effect of TRIMBOW® and RELVAR® on small airways restriction and lung stiffness with specific test measured 5-120 minutes post-dose after 4 weeks of treatment.
• To compare the effect of TRIMBOW® and RELVAR® on other Forced Oscillation Technique (FOT) parameters used to assess the lung function
• To compare the effect of TRIMBOW® and RELVAR® in terms of lung function parameters;
• To compare the effect of TRIMBOW® and RELVAR® in terms of health status and COPD impact on patient health assessed through COPD Assessment Test (CAT);
• To evaluate safety and tolerability of TRIMBOW® and RELVAR®.
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Patients with established diagnosis of COPD at least 12 months prior to the screening visit (according to GOLD Report, revised 2019). Patients with a diagnosis of Asthma COPD Overlap Syndrome (ACOS) and with a current diagnosis of atopy or allergic rhinitis based on their medical history and investigator judgement will be also eligible for inclusion.
- Current smokers or ex-smokers, who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years [pack-years = (number of cigarettes per day x number of years)/20]. If patients underwent any kind of smoking cessation therapy, it should be finished at least 2 months prior to screening.
- A post-bronchodilator FEV1 <60 % of the predicted normal value and a post-bronchodilator FEV1/FVC < 0.7 within 30 min after 4 puffs (4 x 100 µg) of salbutamol pMDI.
- Patients under double or triple therapy for at least 2 months prior to screening visit in stable doses and regimens with either:
a. inhaled corticosteroids/long-acting β2-agonist combination (ICS/LABA) (fixed or free), or
b. inhaled corticosteroids/long-acting muscarinic antagonist free combination (ICS/LAMA), or
c. Inhaled long-acting β2-agonist / long-acting muscarinic antagonist (LABA/LAMA) (fixed or free), or
d. fixed or free combination of an inhaled corticosteroid /long-acting β2-agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA)
- A cooperative attitude and ability to correctly use the study inhalers and spacer.
- Female patients must be either of non-childbearing potential (WONCBP) defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile) or physiologically capable of becoming pregnant (i.e. women of childbearing potential (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 contact or
b. WOCBP with non-fertile male partners (contraception is not required in this case).
For the definition of WONCBP, WOCBP, fertile men, and the list of highly effective birth control methods, refer to Appendix 3 (or section 4.1 of the CTFG guidance).
Any postmenopausal women (physiologic menopause defined as “12
consecutive months of amenorrhea”) or women permanently sterilized (e.g. bilateral oophorectomy, hysterectomy or bilateral salpingectomy) may be enrolled in the study
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| E.4 | Principal exclusion criteria |
- Diagnosis of asthma.
- Patients requiring use of the following medications:
i. A course of systemic steroids longer than 3 days for COPD exacerbation in the 4 weeks prior to screening.
ii. A longer than 7-day course of antibiotics for the treatment of COPD exacerbation in the 4 weeks prior to screening.
iii. Use of antibiotics for a lower respiratory tract infection (e.g pneumonia) in the 4 weeks prior to screening.
- COPD exacerbation requiring prescriptions of systemic corticosteroids and/or antibiotics or hospitalization during the run-in period.
- Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia.
- Known respiratory disorders other than COPD which may impact the efficacy of the study drug according the investigator’s judgment. This can include but is not limited to alfa-1 antitrypsin deficiency, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease.
- Patients who have clinically severe cardiovascular condition (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV, left ventricular failure, acute myocardial infarction, not controlled arrhythmia etc.), which may impact the efficacy or the safety of the study drug according to the investigator’s judgement.
- An abnormal and clinically significant 12-lead ECG which may impact the safety of the patient according to investigator’s judgement. Patients whose electrocardiogram (ECG) (12 lead) shows QTcF >450 ms for males or QTcF >470 ms for females at screening or at randomisation visits are not eligible. The QTcF criterion should not be applicable to patients with pacemaker or permanent atrial fibrillation.
- Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic agents.
- History of hypersensitivity to anticholinergics, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial which may raise contra-indications or impact the efficacy of the study drug according to the investigator’s judgement.
- Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug according to investigator’s judgement.
- Unstable concurrent disease: e.g. fever, uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; uncontrolled gastrointestinal disease (e.g. active peptic ulcer); uncontrolled neurological disease; uncontrolled haematological disease; uncontrolled autoimmune disorders, or other which may impact the efficacy or the safety of the study drug according to investigator’s judgment.
- History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Area under the curve of Reactance (AX) 5 - 120 minutes post-dose after 4 weeks of treatment with Trimbow and Relvar. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The AX will be measured as the average of 5, 15, 30, 60, 90 and 120 minutes post-dose assessments. |
|
| E.5.2 | Secondary end point(s) |
|
| 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 | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | No |
| 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 | 8 |
| E.8.9.1 | In the Member State concerned days | 9 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 8 |
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