E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In healthy volunteers, the aim is to characterise the CSF diclofenac pharmacokinetics following administration of a single bouls of intravenous Dyloject. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066714 |
E.1.2 | Term | Acute pain |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036236 |
E.1.2 | Term | Postoperative pain relief |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054711 |
E.1.2 | Term | Postoperative pain |
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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 |
To characterise the CSF diclofenac pharmacokinetics following administration of intravenous Dyloject. |
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E.2.2 | Secondary objectives of the trial |
To characterise CSF PGE2 levels in the normal uninjured human with or without diclofenac.
To demonstrate the effectiveness of diclofenac on the reduction of the inflammatory marker PGE2 and cytokines.
To examine the relationship between CNS and plasma PGE2 levels
To establish proof of concept for further analyses: An optional continuation of this pilot study is proposed dependant on interim analysis of the first phase.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients aged at least 18 years. 2. Scheduled to undergo surgery performed under spinal anaesthesia 3. Patients must be inpatients 4. Patient has given written informed consent
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E.4 | Principal exclusion criteria |
1. History of bleeding diathesis or use of anticoagulant or antiplatelet agent. 2. History of spinal or neurological disease (incl. raised intracranial pressure), or surgery contraindicating spinal anaesthesia. 3. Use of aspirin within 72 hours prior to surgery. 4. Use of other NSAID’s, paracetamol or steroids within 12 hours before surgery. 5. Hypersensitivity to diclofenac or local anaesthetics. 6. AST, ALT or BUN >1.5x the upper limit of the reference range, or creatinine greater than the upper limit of the reference range. 7. Any other abnormal laboratory results considered clinically significant in relation to this study by the investigator 8. Presence of oliguria, anaemia, hypotension or hypovolaemia 9. Contraindications to NSAID / diclofenac 10. Patients who are unwilling or unable to conform to the protocol 11. Patients who have received an unlicensed drug less than 30 days prior to the study 12. Patients who have been previously admitted to the study. 13. Pregnant or lactating females or females of child-bearing potential who are unwillingto undertake a pregnancy test (urinary B-HCG). 14. A bloody tap (visible blood in CSF) 15. Patients with a hypersensitivity to the excipients Hydroxypropylbetadex (HPβCD) or monothioglycerol. 16. Operations with high risk of haemorrhage. 17. Patients who are considered unsuitable by the responsible anaesthetist - for whom spinal anaesthesia is deemed to constitute an unacceptable, increased risk 18. Patients who are involved in existing research.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point of this study is the laboratory results from the cerebrospinal fluid samples |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 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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Completion of last clinical contact with 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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |