E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This study is designed to look why patients with severe asthma fail to respond to oral corticosteroids in the same way as patients with non-severe disease. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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 |
This study is to establish why severe asthmatic patients do not respond to oral corticosteroids as do non-severe asthmatics - is it due to abnormal/subtherapeutic levels or inability to exert its anti-inflammatory effects? Aims and objectives 1. To evaluate blood prednisolone levels and their anti-inflammatory effects in two severe asthma groups, comparing patients on inhaled corticosteroids (ICS) alone to those on ICS plus oral prednisolone, and a group of well-controlled moderately severe asthmatics. 2. To evaluate if a 14-day course of prednisolone affects ‘spot’(one-off) measurements of prednisolone levels, and if these are influenced by taking regular prednisolone 3. To determine the relationship between blood levels of prednisolone and its anti-inflammatory effects Primary endpoints: 1. serum prednisolone levels over 24 hours 2. change in FEV1 24 hours post prednisolone 3. changes in eNO, sputum eosinophils and inflammatory mediators over 24 hours
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints: 1. difference between day 1 and day 14 in serum prednisolone levels 2. difference in FEV1 between day 1 and day 14 3. difference in eNO, sputum eosinophils and inflammatory mediators between day 1 and day 14 4. changes in asthma control symptoms before and after treatment
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Severe asthma subjects: Physician diagnosis of asthma Aged 18 – 70 Non-smokers or ex-smokers with less than 5 pack/year history Major characteristics (at least one of the following criteria) • Treatment with continuous or near continuous (>50% of year) oral corticosteroids • Requirement for treatment with high dose inhaled corticosteroids (ICS) Minor characteristics (at least 2 out of the following) 1. Requirement for daily treatment with a controller medication in addition to ICS e.g. LABA, theophylline, leukotriene antagonist 2. Asthma symptoms requiring SABA on a daily or near daily basis 3. Persistent airways obstruction (FEV1 <80% predicted, diurnal PEF variation >20%) 4. One or more emergency care visits for asthma per year 5. 3 or more steroid “bursts” per year 6. Prompt deterioration with ≤ 25% reduction in oral or ICS 7. Near fatal asthma event in the past
Moderately-severe asthma: Physician diagnosis of asthma Aged 18 – 70 Non-smokers or ex-smokers with less than 5 pack/year history Less than 2 courses of prednisolone per year Taking up to 2000 mcg of inhaled corticosteroid (BDP equivalent) per day Stable asthma for at least 6 months prior to enrolment
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E.4 | Principal exclusion criteria |
Current smokers, or less than 3 years since quitting smoking Less than 4 weeks from an exacerbation Diabetes Active peptic ulceration Previous history of psychiatric disturbances on high dose prednisolone On steroid-sparing agent or immunosuppressant such as azathioprine, methotrexate and ciclosporin Concomitant anti-IgE therapy Pregnancy
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints: 1. serum prednisolone levels over 24 hours 2. change in FEV1 24 hours post prednisolone 3. changes in eNO, sputum eosinophils and inflammatory mediators over 24 hours 4. levels of activated GR (glucocorticoid receptor) |
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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 | Yes |
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 | 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) | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
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 | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
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 | 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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |