Contact information
Type
Scientific
Primary contact
Prof Saye Khoo
ORCID ID
Contact details
Professor and Hon Consultant Infectious Diseases
University of Liverpool
70 Pembroke Place
Liverpool
L69 3GF
United Kingdom
+44 (0)151 794 5560
khoo@liv.ac.uk
Additional identifiers
EudraCT number
2008-006371-67
ClinicalTrials.gov number
Protocol/serial number
RLBUHT 3729
Study information
Scientific title
Effect of thienopyridine derivative (clopidogrel) on the disposition of efavirenz and neviparine in human immunodeficiency virus (HIV) positive patients: a randomised single-phase multi-dose proof-of-concept study
Acronym
Study hypothesis
The plasma concentration of non-nucleoside reverse transcriptase inhibitors (NNRTIs) (nevirapine and efavirenz) may be pharmacologically enhanced in-vivo through inhibition of CYP2B6 with clopidogrel.
Ethics approval
National Research Ethics Service (Northwest Research Ethics Committee) (UK) approved on the 28th August 2009 (ref: 09/H1010/6)
Study design
Open-label sequential randomised single phase multi-dose proof-of-concept study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Human immunodeficiency virus (HIV)
Intervention
Study patients on nevirapine should be receiving 200 mg 12-hourly. Study patients on efavirenz who are taking 600 mg at night would be converted to 600 mg in the morning as follows: 400 mg mane, 200 mg nocte for 1 day, then 600 mg for 1 day followed by the study day.
Study Day 1:
Patients are fasted from midnight and attend at 08:00 hours without taking their pills. After breakfast and blood sampling for pharmacokinetic profiles patients would then be administered initial dose of clopidogrel (Plavix®, 75 mg once daily; Sanofi Synthelabo, Guildford, United Kingdom) and would self-administer the remaining dose at home for the remaining 6 days.
Joint sponsor details:
The University of Liverpool (UK)
Pembroke Place
Liverpool L69 3GF
United Kingdom
http://www.liv.ac.uk/
Intervention type
Drug
Phase
Not Applicable
Drug names
Efavirenz, nevirapine, clopidogrel
Primary outcome measure
Absolute change (demonstrated by significant difference) in plasma AUC of efavirenz alone or nevirapine alone if the respective 90% classical confidence interval for geometric mean ratio lies within 0.80 - 1.25 of the reference AUC 0 - 24 hours.
All measures determined at the end of the study duration and data analysis (entire study duration is 8 days and data analysis approximately 3 weeks to a month).
Secondary outcome measures
1. Change in Cmax, Cmin, and weight-corrected apparent oral clearance (CL/F)/kg of efavirenz/nevirapine
2. Safety and tolerability of co-administration of clopidogrel and efavirenz/nevirapine
All measures determined at the end of the study duration and data analysis (entire study duration is 8 days and data analysis approximately 3 weeks to a month).
Overall trial start date
15/11/2009
Overall trial end date
15/12/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged greater than 18 years, either sex
2. On efavirenz (EFV) or nevirapine (NVP) containing regimen for greater than or equal to 6 months
3. Viral load less than or equal to 40 copies/ml and any CD4 count
4. No laboratory evidence of NNRTI toxicity:
4.1. Alanine aminotransferase (ALT) less than or equal to upper limit of normal (ULN)
4.2. Bilirubin less than or equal to ULN
4.3. Albumin greater than or equal to 30 g
4.4. Creatinine less than or equal to ULN
5. Not pregnant (for contraception, patients would be advised to use non-oestrogen based contraceptive devices)
6. No inter-current acute illness
7. No past medical history of coronary heart disease
8. No history of bleeding diathesis
9. No history of allergy to thienopyridines
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
37
Participant exclusion criteria
1. Unable to provide informed consent
2. Known or suspected poor adherence to anti-retroviral therapy (ART)
3. Continuing intravenous (IV) drug user
4. On a HIV protease inhibitor or any known P450 inhibitors or inducers
5. Platelets less than or equal to 100 x 10^9/l
6. Neutrophils less than or equal to 1.0 x 10^9/ml
Recruitment start date
15/11/2009
Recruitment end date
15/12/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Professor and Hon Consultant Infectious Diseases
Liverpool
L69 3GF
United Kingdom
Sponsor information
Organisation
Royal Liverpool University Hospital and the University of Liverpools Biomedical Research Centre (UK)
Sponsor details
Royal Liverpool & Broadgreen University NHS Trust
Prescot Street
Liverpool
L7 8XP
United Kingdom
+44(0)151 794 5560
mdanjuma@liv.ac.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
National Institute for Health Research (NIHR) (UK) - through the Royal Liverpool University Hospital and the University of Liverpools Biomedical Research Centre (ref: UoL000399. R&D 3729)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list