Pharmacokinetic investigation into the formation of carbamazepine metabolites and carbamazepine-protein conjugates in healthy volunteers
| ISRCTN | ISRCTN00131154 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN00131154 |
| Clinical Trials Information System (CTIS) | 2012-004700-35 |
| Protocol serial number | 13845 |
| Sponsor | Royal Liverpool and Broadgreen University NHS Trust (UK) |
| Funder | Medical Research Council (MRC) (UK) |
- Submission date
- 22/10/2014
- Registration date
- 22/10/2014
- Last edited
- 21/09/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Carbamazepine is a drug used to treat epileptic seizures and nerve pain. The aim of this study is to test if this drug or its components can bind to proteins within the body and can create allergic reactions for people who are genetically prone to such reactions. We aim to find out the levels of the drug carbamazepine and its components following a single dose of carbamazepine.
Who can participate?
Healthy men aged between 18 and 55 years.
What does the study involve?
Participants will be asked to attend the clinical research unit at the Royal Liverpool Hospital. They will screened for suitability to take part in the study. If suitable they will be asked to return for another visit where they will be prescribed a single dose of carbamazepine. Before taking this dose they will be asked to provide a blood sample and then blood samples will be taken at regular intervals up to 72 hours after taking the drug. Urine samples will also be taken during the 72 hours.
What are the possible benefits and risks of participating?
There will be no direct benefits to participants. The risks of participating include pain and bruising associated with blood sampling. We will minimise this risk as only healthcare professionals trained in taking blood samples will be allowed to perform these procedures.
Where is the study run from?
The Royal Liverpool University Hospital (UK).
When is the study starting and how long is it expected to run for?
August 2013 to December 2013.
Who is funding the study?
Medical Research Council (MRC) (UK).
Who is the main contact?
Dr Vincent Yip
vyip@liv.ac.uk
Contact information
Scientific
Wolfson Centre for Personalised Medicine
Department of Pharmacology
Block A:
Waterhouse Buildings
15 Brownlow Street
Liverpool
L69 3GL
United Kingdom
| Phone | +44 151 794 5543 |
|---|---|
| vyip@liv.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Non-randomised; Interventional; Design type: Not specified, Treatment |
| Secondary study design | Non randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Pharmacokinetic investigation into the formation of carbamazepine metabolites and carbamazepine-protein conjugates in healthy volunteers: a non-randomised study |
| Study acronym | PICME |
| Study objectives | Carbamazepine or carbamazepine metabolites are reactive and can bind intracellular proteins that stimulate hypersensitivity reactions in patients with genetic suscepitibility. |
| Ethics approval(s) | 18/12/2012, ref: 12/NW/0780 |
| Health condition(s) or problem(s) studied | Topic: Genetics; Subtopic: Genetics Research and Congenital Disorders (all subtopics); Disease: Genetics Research and Congenital Disorders |
| Intervention | Healthy volunteers will be given a single 400 mg dose of carbamazepine Follow Up Length: 1 month(s); Study Entry: Registration only |
| Intervention type | Other |
| Primary outcome measure(s) |
Pharmacokinetic analyses; Timepoint(s): pre-dose, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours; Methods: High performance liquid chromatography and tandem mass spectrometry |
| Key secondary outcome measure(s) |
Not provided at time of registration |
| Completion date | 30/12/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Male |
| Target sample size at registration | 8 |
| Total final enrolment | 8 |
| Key inclusion criteria | 1. Subject is willing and able to give written informed consent 2. Healthy male subjects between 18 and 55 years of age inclusive 3. Subjects body weight is between 50 and 100 kg 4. Subjects body mass index is between 18 and 32 kg/m2 |
| Key exclusion criteria | 1. Subject is not willing to take part or unable to give written informed consent 2. Subject has clinically significant abnormal medical history or physical exam 3. Subject has history of febrile illness within 4 weeks prior to admission 4. Subject has clinically significant abnormal laboratory test at screening including HBV/HCV/HIV 5. Subject has taken any interacting prescription or non-prescription drug, or dietary supplements within 2 weeks prior to study admission. Herbal supplements must be discontinued at least 4 weeks prior to admission to the clinical research facility 6. Subject possesses either the HLA-B*1502 or HLA-A* 3101 genotype 7. Subject has a clinically significant ECG abnormality prolonged corrected QT >450 ms, 2nd or 3rd degree atrioventricular conduction block 8. Subject has known hypersensitivity to carbamazepine or structurally related drugs (e.g. tricyclic antidepressants) or any other component of the formulation 9. Subject with history of bone marrow depression 10. Subject with history of hepatic porphyrias (e.g. intermittent porphyria, variegate porphyria, porphyria cutanea tarda) 11. Subject has taken part on another research study within 90 days of commencement 12. Subject has any condition which in the opinion of the investigator will interfere with the study |
| Date of first enrolment | 24/07/2013 |
| Date of final enrolment | 30/12/2013 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
L69 3GL
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/06/2021 | 21/09/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
21/09/2021: Publication reference added.
19/02/2020: The following changes have been made:
1. A thesis link has been added to the publication and dissemination plan.
2. The final enrolment number has been added from the thesis.
02/06/2017: No publications found in PubMed, verifying study status with principal investigator
