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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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 evaluate effect of Symbicort on HDAC and HAT activities ratio in macrophages of induced sputum in COPD patients in comparison with the effect Pulmicort (budesonide) and placebo treatment. |
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E.2.2 | Secondary objectives of the trial |
Several inflammation or anti-inflammation markers and lung function will be evaluated as shown below
Induced sputum Cells: o Differential cell counts o HDAC-1,-2,-5, HAT and CREB binding protein (CBP) mRNA expression by Quantitative RT-PCR o GRE and NF-kB activity by TransAM method o mRNA expression of IL-8, MCP-1, GRO-alpha and MMP9 if enough sample has been obtained (see 8.6)
Supernatant: o IL-8, MCP-1, GRO-alpha (ELISA) o MMP9 activity (Fluorometric assay)
Exhaled breath condensate 8-isoprostane, LTB4 (ELISA)
Exhaled Nitric Oxide (NO) using the multiple expiratory flow technique to measure peripheral production of NO
Lung function (Spirometry -FEV1, FVC, FEV1/FVC)
Impulse oscillometry (IOS)- 4 tests (each one lasting 1 minute)
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion Criteria-Healthy non-smokers • Non-smoking volunteer • aged 40 –75 years (age matched to COPD patients) • Normal spirometry (normal FEV1/FVC ratio >70% and FEV1>80% predicted) • Subjects are able to give informed consent
Inclusion Criteria-COPD patients (stage II-III according to the GOLD guidelines13) • Current and/or ex-smokers with no less than 10 pack-year smoking history • aged 40 –75 years • FEV1 bigger than or equal to 30% and less than 80% of predicted (the upper value is a prostbronchodilator value) • FEV1/FVC < 70% • Patients with stable COPD • Inhaled Corticosteroid (ICS) treatment, if exists, must be stopped for 2 weeks prior the study treatment • Long-acting beta2-agonists and theophylline need to be stopped at least 3 days before run-in , but anti-cholinergics will be allowed throughout the study • The subjects are able to give informed consent
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E.4 | Principal exclusion criteria |
Exclusion Criteria-Healthy non-smokers • Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator • Upper respiratory infection within the last 4 weeks • Subjects who have received research medication within the previous one month • Subjects unable to give informed consent • Any psychiatric condition rendering the patient unable to understand the nature, scope and possible consequences of the study.
Exclusion Criteria-COPD patients • Evidence of asthma • Bronchodilator reversibility > 12% • Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator • Patients who have had oral steroids within 8 weeks prior to the screening visit.
• Patients who are already on ICS and in which it is considered unsafe (as judged by the Investigator) to stop this treatment for the study period. • Patients who have had an exacerbation which required treatment with oral steroids during the last 2 months prior to the screening visit. • Upper respiratory infection within the last 4 weeks • Subjects who have received research medication within the previous one month • Subjects unable to give informed consent • Any psychiatric condition rendering the patient unable to understand the nature, scope and possible consequences of the study • Patients with significant co-morbidities as judged by the investigator • Any other respiratory disease, which is considered by the investigator to be clinically significant
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E.5 End points |
E.5.1 | Primary end point(s) |
HDAC and HAT activity ratio |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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The last visit of the last subject. |
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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 | 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 |