The Cerebrospinal Fluid (CSF) pharmacokinetics of a single pre-operative intravenous bolus dose of diclofenac (Dyloject) in comparison of diclofenac infusion (Voltarol) - Dyloject CSF Pharmacokinetics

Phase 1

• Conditions: In healthy volunteers, the aim is to characterise the CSF diclofenac pharmacokinetics following administration of a single bouls of intravenous Dyloject.; MedDRA version: 9.1 Level: LLT Classification code 10066714 Term: Acute pain; MedDRA version: 9.1 Level: LLT Classification code 10036236 Term: Postoperative pain relief; MedDRA version: 9.1 Level: LLT Classification code 10054711 Term: Postoperative pain

• Registration Number: EUCTR2008-007309-35-GB
• Lead Sponsor: Barts and The London NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-01-20
• Study Completion: 2010-05-21
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 0

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 (HPßCD) 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To characterise the CSF diclofenac pharmacokinetics following administration of intravenous Dyloject.;<br> Secondary Objective: To characterise CSF PGE2 levels in the normal uninjured human with or without diclofenac.<br><br> To demonstrate the effectiveness of diclofenac on the reduction of the inflammatory marker PGE2 and cytokines.<br><br> To examine the relationship between CNS and plasma PGE2 levels<br><br> 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.<br> ;Primary end point(s): The primary end point of this study is the laboratory results from the cerebrospinal fluid samples