E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with moderate to very severe chronic obstructive pulmonary disease (COPD) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by chronic obstruction of lung airflow that interferes with normal breathing and is not fully reversible. |
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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 efficacy in reducing exacerbations with Symbicort pMDI 160/4.5 μg x 2 actuations BID versus formoterol Turbuhaler 4.5 μg x 2 inhalations BID in COPD subjects |
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E.2.2 | Secondary objectives of the trial |
To compare Symbicort pMDI and formoterol Turbuhaler treatments on the time to the first COPD exacerbation
To compare Symbicort pMDI and formoterol Turbuhaler treatments on health status/health-related quality of life
To compare Symbicort pMDI and formoterol Turbuhaler treatments on pulmonary function
To compare Symbicort pMDI and formoterol Turbuhaler treatments on rescue medication use
To compare Symbicort pMDI and formoterol Turbuhaler treatments on nocturnal awakenings
To demonstrate the safety of Symbicort pMDI compared to that of formoterol Turbuhaler in subjects with COPD |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed Informed Consent at Visit 1 obtained prior to conducting any study-related procedures including withdrawal of medications.
2. Outpatients; men or women ≥40 years of age.
3. A current clinical diagnosis of COPD with COPD symptoms for more than 1 year, according to the GOLD guidelines.
4. Current or previous smoker with a smoking history equivalent to 10 or more pack years (1 pack year = 20 cigarettes smoked per day for 1 year).
5. Post-bronchodilator FEV1/forced vital capacity (FVC) <0.7 (70%) and FEV1 ≤70% of predicted normal (PN) value.
6. Documented use of a short-acting inhaled bronchodilator (β2-agonists or anticholinergics) as rescue medication within 6 months prior to study start.
7. A score of ≥2 on the modified medical research council (MMRC) dyspnea scale.
8. Documented history of ≥1 moderate or severe COPD exacerbation(s) that required treatment with systemic (oral, IM, IV) corticosteroids (a minimum 3 day course of an oral corticosteroid treatment or single depot corticosteroid injection), or hospitalization (defined as an inpatient stay or >24 hour stay in an observation area in the emergency department or other equivalent facility depending on the country and healthcare system) within 2-52 weeks before Visit 1 (i.e., not within the 14 days prior to Visit 1). A history of an exacerbation treated exclusively with antibiotics will not be considered adequate.
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E.4 | Principal exclusion criteria |
1. A history of asthma at or after 18 years of age.
2. Subjects with significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure (including significant cor pulmonale), uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator.
3. Known homozygous alpha-1 antitrypsin deficiency.
4. Any significant disease or disorder (e.g., gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results of the study, or the subject’s ability to participate in the study.
5. A history of malignancy (except basal cell carcinoma) within the past 5 years.
6. Active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease, or other active pulmonary diseases.
7. Subjects who have needed additions or alterations to their usual maintenance or change in formulation of rescue therapy for COPD due to worsening symptoms within the 14 days prior to Visit 1 and up to Visit 3.
8. CXR (frontal and lateral) with suspicion of pneumonia or other condition/abnormality that will require additional investigation/treatment, or put the subject at risk because of participation in the study.
9. Risk factors for pneumonia: immune suppression (HIV, lupus) or other risk for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson’s disease, myasthenia gravis, etc.).
10. Pneumonia not resolved within 14 days of Visit 1.
11. Moderate or severe COPD exacerbation that has not resolved within 14 days prior to Visit 1 or a moderate or severe COPD exacerbation that occurs between Visit 1 and Visit 2.
12. Long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day.
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E.5 End points |
E.5.1 | Primary end point(s) |
The rate of moderate and severe COPD exacerbations defined as:
Worsening of ≥2 major symptoms or worsening of 1 major symptom together with ≥1 minor symptom for ≥2 consecutive days.
Moderate exacerbation: treatment of symptoms with systemic corticosteroids (≥3 days) and/or antibiotics.
Severe exacerbation: symptoms that require hospitalization (including >24 hours in ED/urgent care setting).
Major symptoms:
• Dyspnea
• Increase in sputum volume
• Increase in sputum color/purulence
Minor symptoms:
• Sore throat
• Colds (nasal discharge and/or nasal congestion)
• Fever without other cause
• Increased cough
• Increased wheeze |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study Visit:
Enrolment W -5
Run-in W -4
Randomization W 0
Treatment W 4, 8, 17
EoT W 26
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E.5.2 | Secondary end point(s) |
• Time to first moderate or severe COPD exacerbation
• St. George’s Respiratory Questionnaire (SGRQ)
• Pre-dose/pre-bronchodilator FEV1 at the study site
• Total rescue medication use (average puffs/day)
• Nights with awakening due to COPD
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Study Visit:
Enrolment W -5
Run-in W -4
Randomization W 0
Treatment W 4, 8, 17
EoT W 26
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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 | No |
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 | No |
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 | 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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Argentina |
Bulgaria |
Chile |
Czech Republic |
Germany |
Mexico |
Poland |
South Africa |
Spain |
United States |
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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
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 8 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 8 |