E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The intended indication for the product under development is that of acute lung injury. |
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E.1.1.1 | Medical condition in easily understood language |
Inflammation of the lungs |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10069351 |
E.1.2 | Term | Acute lung injury |
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 main aim of this study is to look at the effects of a drug called aspirin at reducing inflammation in the lungs compared to a placebo(dummy) drug in healthy volunteers after inhalation of a substance which causes a low level of inflammation in the lungs without any adverse effects. |
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E.2.2 | Secondary objectives of the trial |
The secondary aims of this study are to examine other important mechanisms by which aspirin may work in reducing lung inflammation and injury. If a beneficial effect was confirmed, a phase 2/3 clinical trial to determine effectiveness and safety of aspirin in patients with ALI/ARDS would be required. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: 1. Healthy non-smoking subjects
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E.4 | Principal exclusion criteria |
Exclusion criteria: 1. Age < 18 years 2. Pregnancy or breast feeding or woman of childbearing potential not using adequate contraception. 3. Participation in a clinical trial of an investigational medicinal product within 30 days 4. Consent declined 5. Aspirin or non steroidal anti-inflammatory (NSAID) use in the past 4 weeks 6. History of asthma 7. Known aspirin or NSAID hypersensitivity 8. History of peptic ulcer disease 9. Platelet count < 150 x 106/ml 10. Aspirin resistance
Aspirin resistance is uncommon and therefore it is not anticipated that it will have a significant impact on the study. However subjects who do not show a change in measures of aspirin responsiveness following aspirin will be excluded. Aspirin responsiveness will be measured by Optical Platelet Aggregometry
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome for this study is BAL IL-8 concentration at 6 hours following LPS administration. This endpoint was chosen as dysregulated alveolar inflammation is important in the development of lung injury and aspirin has a range of anti-inflammatory effects. Specifically IL-8 is a potent neutrophil chemoattractant present in the alveolar space early in course of ALI , treatment with anti-IL-8 monoclonal antibody in experimental animal models of lung injury has been shown to attenuate injury and increased plasma IL-8 is associated with mortality in ALI suggesting that it is important in the pathophysiology of lung injury.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
BAL IL-8 concentration will be measured at 6 hours following LPS administration, following 7 days treatment with aspirin or placebo. |
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E.5.2 | Secondary end point(s) |
The secondary outcomes are to investigate if pre-treatment with aspirin will modulate:
1. Alveolar inflammatory response 2. Plasma inflammatory response 3. Intracellular signalling activity in the alveolar space 4. Indices of alveolar epithelial and endothelial function and injury 5. Lipid inflammatory mediators
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
These secondary endpoints will be measured in BAL at 6 hours and in plasma at 24 hours following LPS administration, following 7 days treatment with aspirin or placebo. |
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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 | 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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | Yes |
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 trial will end when the completed number of patients have been recruited and completed follow-up.
The trial will be stopped prematurely if: • Mandated by the Ethics Committee • Mandated by the MHRA • Mandated by the sponsor eg following recommendations from the DMEC • Funding for the trial ceases
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 30 |