E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
The hypothesis of the study is that treatment with simvastatin for 4 days will reduce pulmonary inflammation induced by LPS inhalation in humans.
The primary outcome measure will be a reduction in bronchoalveolar lavage (BAL) CXCL8 concentration between the simvastatin and placebo treated groups.
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E.2.2 | Secondary objectives of the trial |
The secondary aims are to investigate if treatment with simvastatin will modulate: 1) alveolar inflammatory response 2) plasma inflammatory response 3) alveolar matrix metalloproteinase activity 4) intracellular signalling in the alveolar space 5) indices of alveolar epithelial and endothelial function and injury to determine the potential mechanisms by which simvastatin may be beneficial in ALI.
The risk of adverse effects of simvastatin is dose dependent but on the basis of current evidence it is unknown if lower doses of simvastatin attenuate the mechanisms important in the development of lung injury. A pilot study of simvastatin 80mg in the treatment of ALI/ARDS is currently ongoing (EudraCT number: 2006-001414-33). If a beneficial effect was confirmed, a large phase 3 clinical trial to determine effectiveness and safety of simvastatin in patients with ALI/ARDS would be required. This current study would inform the rationale for the dose of simvastatin to be used.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Healthy non-smoking subjects |
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E.4 | Principal exclusion criteria |
• age < 18 years • creatinine kinase (CK) > 5 times upper limit normal range • known active liver disease, alcohol abuse or abnormal liver function tests: transaminases > 3 times upper limit normal range • renal impairment (calculated creatinine clearance less than 60mL/minute) • known lactose intolerance • history of asthma • participation in other trials within 30 days • pregnancy, breast-feeding or women of childbearing potential not using adequate contraception; • current treatment with statins • known hypersensitivity to the study medication • a previous adverse reaction to statins • concomitant use of fibrates or other lipid-lowering therapy • concomitant use of itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, grapefruit juice, cyclosporine, danazol, amiodarone, verapamil or diltiazem . • consent declined
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure will be a reduction in BAL CXCL8 concentration between the simvastatin and placebo treated groups. |
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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 | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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.8.3 |
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 | 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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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 | |
E.8.9.1 | In the Member State concerned days | |