| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic obstructive pulmonary disease (COPD) |
|
| 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 assess the effects of GFF relative to UV on lung function as measured by trough FEV1 in patients with moderate to very severe COPD |
|
| E.2.2 | Secondary objectives of the trial |
1. To further assess the effects of GFF relative to UV on lung function.
2. To assess the effects of GFF relative to UV on dyspnea
3. To assess the effects of GFF relative to UV on symptoms of COPD
4. To assess the effects of GFF relative to UV on health-related quality of life |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Provision of informed consent prior to any study specific procedures
2. Female or male patients aged 40-95 years inclusive at the time of enrolment at screening
3. Tobacco Use: Current or former smoker with a history of at least 10 pack-years of cigarette smoking (1 pack year = 20 cigarettes smoked per day for 1 year)
4. A current clinical diagnosis of COPD, with COPD symptoms for more than 1 year prior to screening, as defined by GOLD criteria or other current guidelines
5. COPD Severity defined as:
- At screening visits, post-bronchodilator FEV1/FVC ratio <0.70, FEV1 <80% of predicted normal value, and FEV1 ≥750 mL if FEV1 is <30% of predicted normal value
- At randomisation, FEV1/FVC ratio <0.70 and FEV1 <80% of predicted normal value in both pre-dose assessments
6. COPD treatment with rescue medication only, or stable dose of maintenance monotherapy (LAMA, LABA or ICS), or stable dose of double maintenance therapy (LAMA/LABA or ICS/LABA), for one month prior to screening. Triple maintenance therapy (LAMA/LABA/ICS) is not allowed for one month prior to screening. Stepping-down from triple maintenance therapy before the month prior to screening must only be based on clinical symptoms in the opinion of the Investigator
7. COPD symptom severity: CAT ≥10 at screening for patients on rescue medication only or maintenance monotherapy. No symptom requirement at screening for patients on double maintenance therapy. CAT ≥10 at randomisation for all patients
8. Patient is willing and, in the opinion of the Investigator, able to adjust current COPD therapy as required by the protocol
9. Documentation of a chest x-ray (as per local practice) or computed tomography (CT) within 6 months prior to screening, with no clinically significant pulmonary abnormalities other than related to COPD
- Specific to countries with restrictive radiology assessment practice: if no documentation of chest x-ray or CT of the chest/lungs within 6 months prior to screening is available, an MRI may be used instead, as per local practice assessment, or the Investigator may follow local guidelines to have the chest x-ray or CT approved
10. Ability and willingness to comply with all study procedures, including daily completion of ePRO |
|
| E.4 | Principal exclusion criteria |
1. Respiratory disease:
- Current diagnosis of asthma
- Alpha-1 Antitrypsin Deficiency as the cause of COPD
- Other respiratory disorders: active tuberculosis, lung cancer, clinically significant bronchiectasis disease, sarcoidosis, IPF, primary pulmonary hypertension, or uncontrolled sleep apnea
- Patients who have undergone lung volume reduction surgery, lobectomy or bronchoscopic lung volume reduction in 1yr of screening
- Severe COPD exacerbation (resulting in hospitalisation) not resolved in 8wk prior to screening, or moderate not resolved in 4wk, or moderate or severe during screening
- Pneumonia or lower respiratory tract infection that required antibiotics in 8wk prior to or during screening
- Risk factors for pneumonia: immune suppression (HIV), severe neurological disorders affecting control of the upper airway or other risk factors that would put patients at substantial risk of pneumonia
- Patients receiving long-term-oxygen therapy or nocturnal oxygen therapy required>12h/day
- Patient use of any non-invasive positive pressure ventilation device. Note: Patients using continuous positive airway pressure or bi-level positive airway pressure for sleep apnea syndrome are allowed if not used for ventilatory support
- Patients who have participated in the acute phase of a pulmonary rehabilitation in 4wk prior to screening or who will enter the acute phase of a pulmonary rehabilitation during screening. Allowed in the maintenance phase
2. Cardiac disease:
- Unstable angina/acute coronary syndrome, or CABG, PCI or myocardial infarction within the past 6 months.
- CHF NYHA class III/IV
- Structural heart disease (hypertrophic cardiomyopathy, significant valvular disease)
- Paroxysmal (in past 6mths) or symptomatic chronic cardiac tachyarrhythmia
- LBB or high-degree AV block (2 and 3 degree) unless using pacemaker
- Sinus node dysfunction with pauses
- Ventricular pre-excitation and/or Wolff-Parkinson-White syndrome
- QTcF interval >470 msec (corrected using Fridericia's formula)
- Any other ECG abnormality deemed clinically significant
- Bradycardia with ventricular rate <45bpm
- Uncontrolled hypertension >165/95mmHg
3. Patients with a calculated eGFR <30mL/min using CKD-EPI formula
4. Patients who have cancer that has not been in complete remission for at least 5yrs
5. Patients with a diagnosis of narrow-angle glaucoma that hasn't been adequately treated. All medications approved for control of intraocular pressures are allowed
6. Patients with symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that is clinically significant
7. Significant diseases or conditions other than COPD which may put the patient at risk, influence the results of the study or the patient's ability to participate
8. Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalyses, vital signs or ECG which may put the patient at risk
9. Pregnant or lactating women, or if planning to become pregnant during the study, or women of childbearing potential who are not using an acceptable method of contraception
10. Patients who have a history of hypersensitivity to β2 agonists, GP or other muscarinic anticholinergics, or any component of the MDI or DPI
11. Patients who abuse alcohol or drugs
12. Patients who are medically unable to withhold their short-acting bronchodilators for 6h prior to spirometry at study visits
13. Patients who would be unable to abstain from protocol-defined prohibited medications during screening and treatment
14. Patients unable to comply with study procedures during screening, including non-compliance (<70%) with ePRO completion
15. Site staff or their immediate family
16. Patients with a history of psychiatric disease, intellectual deficiency, poor motivation, substance abuse, or other conditions that will limit the validity of informed consent to participate in the study as judged by Investigator
17. Treatment with IP or device in another clinical study within the last 30d or 5 1/2-lives prior to screening, whichever is longer. Note: Patient participation in observational studies is not exclusionary
18. Patients who have needed additions or alterations to their usual maintenance therapy for COPD due to worsening symptoms within 1 mth prior to and during screening
19. Treatment with depot corticosteroids within 6wk, and other systemic corticosteroids within 4 wk, prior to screening. Except patients who are steroid dependent, and maintained on an equivalent of 5mg prednisone per day, or 10mg every other day, for at least 3mths prior to screening, provided stable dose during screening
20. Any monoclonal or polyclonal antibody therapy taken for any reason within 6mths prior to screening
21. Planned hospitalisation or significant surgical procedure during the study
22. Involvement in the planning and/or conduct of study (both sponsor and study site)
23. Previous randomisation in the present study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in morning pre-dose trough FEV1 (Forced Expiratory Volume in 1 second) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Onset of action on day 1; proportion of patients with increase of FEV1 of ≥100 ml from baseline at 5 minutes
Change from baseline in Peak FEV1 within 2 hours post-dosing
Change from baseline in Peak Inspiratory Capacity (IC) within 2 hours post-dosing
Transition Dyspnea Index (TDI) focal score
Change from baseline in Early Morning Symptoms COPD Instrument (EMSCI) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 5 minutes on Day 1 for early onset, 24 weeks for all other endpoints |
|
| 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 | Yes |
| 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) | Yes |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Umeclidinium/Vilanterol fixed-dose combination |
|
| 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 | 15 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 43 |
| 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 |
| Canada |
| France |
| Hungary |
| Russian Federation |
| Ukraine |
| United States |
|
| 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
|
| The last visit of the last patient undergoing the study |
|
| 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 | 3 |
| 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 | 3 |
Print
