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 |
Chronic Obstructive Pulmonary Disease (COPD) |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 research question is whether inhaled drug treatments in combination (long-acting beta-2-agonists (LABA) together with inhaled corticosteroid (ICS)), that are routinely used for chronic obstructive pulmonary disease (COPD) patients can improve inflammation in the cells of the sputum/mucus from these patients compared to either drug component alone. |
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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 |
1. Patients (n=35) with chronic obstructive pulmonary disease (COPD) with mild-to-moderate disease severity (GOLD 1 and 2 guidelines). The post-bronchodilator FEV1 will be used in the criteria to define GOLD severity. 2. Aged 38-80 years inclusive 3. FEV1 <15% reversibility (not % predicted) and/or an increase of <200 ml after inhaled β2-agonists (400 μg salbutamol) 4. Patients will be allowed to use their current short-acting β2-agonists (SABA) and long-acting β2-agonists (LABA) and short-acting muscarinic-antagonist (SAMA) and long-acting muscarinic-antagonists (LAMA). However they should refrain from short-acting β2-agonists (SABA) and short-acting muscarinic-antagonist (SAMA) for 6 hours before the study visit and for long-acting β2-agonists (LABA) and long-acting muscarinic-antagonists (LAMA) at least 12 hours before the study visit, unless needed by the patient’s clinical condition. 5. Theophylline (an oral tablet bronchodilator) will be required to be stopped at least 3 days prior to start of Study Visit one, and patients will not be allowed this treatment during the study as it may affect the GR response and the bronchodilator (lung function, spirometry) responses. 6. Capable of giving informed consent. |
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E.4 | Principal exclusion criteria |
1. As a result of the medical interview, physical examination or screening investigations, the Physician Responsible considers the volunteer unfit for the study. 2. Patients who have a clinical diagnosis of Asthma, as decided by the Study Investigators, as this does not fulfil the diagnosis of chronic obstructive pulmonary disease (COPD). 3. Patients who have had a history of an upper or lower respiratory infection (including sinusitis) within 4 weeks prior to study entry, as this can affect the breathing response. 4. Patients who have received oral or parenteral steroids within 4 weeks prior to study entry, as this can affect the breathing response and signifies that their condition needs to be controlled better. 5. Patients who have been hospitalised for a COPD exacerbation within 1 month of study entry and/or has received antibiotics within 4 weeks of study entry, as this signifies that their condition needs to be controlled better. 6. Patients taking any regular medication that is contraindicated (as indicated in the British National Formularly) in those about to receive the study medications listed in this protocol; other than the oral contraceptive pill. 7. Any evidence of a positive pregnancy urine test for female volunteers or females who are pregnant or lactating or are likely to become pregnant during the trial. Women of child−bearing potential may be included in the study if, in the opinion of the investigator, they are taking adequate contraceptive precautions (whihc will be directly enquired at the screening visit). 8. Patients who have a history of drug allergy which, in the opinion of the Unit Physician, contraindicates his/her participation in the study. 9. Patients with a known or suspected allergy to corticosteroids or any component of the formulations and/or suspected hypersensitivity to inhaled corticosteroid (this will be asked directly at the screening visit). 10. Patients who regularly, or on average, drink more than 21 units of alcohol (males) and 14 units of alcohol (female) per week (this will be asked directly at the screening visit). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is to investigate whether treatment with a single inhaled dose of Symbicort ®-800 or Symbicort ®-400 (a combination of a LABA - formoterol and an ICS – budesonide) will be reflected by changes in GR activation in sputum (on GR-GRE binding in sputum macrophages) that will be equal or superior to a single inhaled clinical dose of ICS alone (at double dose; that is, Pulmicort ®-800 = budesonide). |
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E.5.2 | Secondary end point(s) |
The secondary outcome measures are: The secondary outcome measures are: (i) To investigate whether there are changes in GR activation in sputum (on GR-GRE binding in sputum macrophages) between; -Symbicort-800 ® (a combination of a LABA - formoterol and an ICS - budesonide) and baseline pre-treatment screening levels -Symbicort-800 ® (a combination of a LABA - formoterol and an ICS - budesonide) and LABA alone (formoterol, FORM) -Symbicort-400 ® (a combination of a LABA - formoterol and an ICS - budesonide) and baseline pre-treatment screening levels -Symbicort-400 ® (a combination of a LABA - formoterol and an ICS - budesonide) and LABA alone (formoterol, FORM) -Symbicort-800 ® (a combination of a LABA - formoterol and an ICS - budesonide) and lower dose Symbicort-400 ® (a combination of a LABA - formoterol and an ICS - budesonide) (ii) To investigate all treatment comparison effects (see primary and secondary (i) objectives above) on; -differential cell counts obtained from induced sputum -and relate changes in GR activation in induced sputum (on GR-GRE binding in sputum macrophages) and selected inflammatory biomarkers in sputum to other clinical (lung function) parameters |
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | 4 |
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 | No |
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
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End of trial would be the last visit of the last patient recruited. |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |