Does a lipid formulation increase the absorption of cannabidiol?
| ISRCTN | ISRCTN18067579 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18067579 |
| EudraCT/CTIS number | 2020-004551-33 |
| IRAS number | 288415 |
| ClinicalTrials.gov number | NCT05032807 |
| Secondary identifying numbers | IRAS 288415 |
- Submission date
- 09/09/2021
- Registration date
- 30/09/2021
- Last edited
- 04/01/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English Summary
Background and study aims
Cannabidiol (CBD) is an approved treatment for epilepsy and could be an effective treatment for psychosis, anxiety and addictions. It has poor oral bioavailability (around 5-10% in the fasted state) which can increase by up to 5 times with food. As a result, patients must carefully schedule their medication according to mealtimes. One way to improve the bioavailability and reduce the food effect is by using a lipid encapsulation.
The CBD formulation used in this study includes a range of fats that improve absorption . The lipids are all EU approved and have been used in medicinal products before.
This study will compare the pharmacokinetics (absorption, clearance etc) of this novel lipid formulation of CBD with a standard formulation. It will use a dose of 1000mg as this is the dose that is effective in patients with schizophrenia.
Who can participate?
Healthy volunteers aged 18 - 45 years
What does the study involve?
Each participant will attend for two experiments where they will be administered one of the two drugs, in a randomised order. They will then provide blood samples over the following 48 hours. The risks associated with taking part are minimal. Participants will be reimbursed for their time.
What are the possible benefits and risks of participating?
Participants will be reimbursed for their time.
The risks associated with taking part are minimal.
Where is the study run from?
King's College London (UK)
When is the study starting and how long is it expected to run for?
August 2020 to September 2022
Who is funding the study?
National Institute for Health Research (NIHR) (UK).
Who is the main contact?
Dr Edward Chesney, edward.chesney@kcl.ac.uk
Contact information
Public
King's College London
London
SE5 8AF
United Kingdom
 ORCID ID |
0000-0003-2851-5252 |
|---|---|
| Phone | +44 (0)7711887754 |
| edward.chesney@kcl.ac.uk |
Study information
| Study design | Single-centre double-blind two-period crossover pharmacokinetic study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request participant information sheet. |
| Scientific title | Pharmacokinetic study of a novel lipid formulation of cannabidiol (CBD) compared to a standard formulation |
| Study acronym | CLIP |
| Study hypothesis | The novel formulation will increase the AUCinf for a single dose of oral CBD in the fasting state. |
| Ethics approval(s) | Approved 11/04/2022, Brent Research Ethics Committee (Skipton House, 80 London Road, London SE1 6LH; +44 (0)20 7104 8128; brent.rec@hra.nhs.uk), ref: 22/LO/0047 |
| Condition | Pharmacokinetics of a novel CBD formulation in healthy participants |
| Intervention | Participants are randomised by computer to receive oral administration of a single dose of either cannabidiol novel formulation 1000mg or cannabidiol standard formulation 1000mg. Followed by blood sampling over 48 hours. At a second appointment, the participant will receive the opposite intervention. There will be a minimum of 2 weeks between appointments. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Cannabidiol novel formulation, cannabidiol standard formulation |
| Primary outcome measure | AUCinf in the fasting state measured using high-performance liquid chromatography/mass spectrometry of blood samples taken over 48 hours |
| Secondary outcome measures | Measured using high-performance liquid chromatography/mass spectrometry of blood samples taken over 48 hours: 1. Maximum plasma concentration (Cmax) 2. Time after administration of drug when maximum plasma concentration is reached (Tmax) 3. Plasma half-life (t½) 4. Area under the concentration-time curve from time zero to 48hours (AUC0-48) |
| Overall study start date | 01/08/2020 |
| Overall study end date | 01/09/2022 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Both |
| Target number of participants | 14 |
| Total final enrolment | 14 |
| Participant inclusion criteria | Current inclusion criteria as of 13/04/2022: 1. Healthy volunteers. Defined as healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine. 2. Aged 18-45 years 3. Agree to fast 15 hours, i.e. 10 pm to 1 pm on dosing days 4. Capable of giving informed consent 5. Written informed consent from participant _____ Previous inclusion criteria: 1. Healthy volunteers 2. Age 18-45 years 3. Females of childbearing potential and males must be willing to use highly effective method of contraception (hormonal or barrier method of birth control; abstinence) throughout the duration of the study and for at least 4 weeks after 4. Agreeing to fast 15 hours; 10pm-1pm on dosing days 5. Capable of giving informed consent 6. Written informed consent from participant |
| Participant exclusion criteria | Current exclusion criteria as of 13/04/2022: 1. Clinically relevant medical history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the participant 2. Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer’s participation in the trial or make it unnecessarily hazardous 3. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any neurological or mental illness 4. Surgery or medical condition that might affect absorption of medicines 5. Blood pressure and heart rate in supine position at the screening examination outside the following ranges. Repeat measurements are permitted if values are borderline (i.e. values that are within 5 mm Hg for blood pressure or 5 beats/min for heart rate) or if requested by the investigator. Subjects can be included if the repeat value is within range or still borderline but deemed not clinically significant by the investigator. 5.1. Blood pressure 90–140 mm Hg systolic, 40–90 mm Hg diastolic 5.2. Heart rate 40–100 beats/min 6. Loss of more than 400 ml blood during the 3 months before the trial, e.g. as a blood donor 7. Any prescribed medication (apart from contraceptives) 8. Use of any CBD products within 6 months of IMP administration 9. Use of any over-the-counter medications or health supplements within the past 2 weeks 10. BMI <18 or >30 kg/m2 11. History of alcohol or substance misuse disorder 12. Intake of more than 14 units of alcohol weekly. 13. Smokes more than 10 cigarettes per day 14. Use of any illicit substances within the last 6 months 15. Pregnant or breastfeeding 16. Women of childbearing potential (as defined in CTFG guidelines, see 5.7 Concomitant Medication) not willing to use a highly effective form of contraception (as defined in CTFG guidelines, see section 5.7 Concomitant Medication) during participation in the study or male patients not willing to ensure use of a condom during participation in the study 17. eGFR ≤70 ml/min 18. Any liver function or renal function test abnormality. A repeat is allowed on one occasion for determination of eligibility. 19. Urine drug screen positive for any substances 20. Positive alcohol breath test 21. Participant in any other clinical trial or experimental drug study in the past 3 months 22. Known hypersensitivity to CBD and/or SEEK formulation excipients 23. Not able to swallow capsules _____ Previous exclusion criteria: 1. Any prescribed medication (apart from contraceptives) 2. Use of any CBD products within six months of IMP administration 3. Use of any over-the-counter medications or health supplements within the past 2 weeks 4. BMI <18 or >30.0 kg/m² 5. History of alcohol or substance misuse disorder 6. Smokes more than 10 cigarettes per day 7. Use of any illicit substances within the last six months 8. Pregnant or breastfeeding 9. eGFR ≤70 mls/min 10. Any liver function or renal function test abnormality 11. Urine drug screen positive for any substances |
| Recruitment start date | 20/04/2022 |
| Recruitment end date | 01/08/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
16 De Crespigny Park
London
SE5 8AF
United Kingdom
Sponsor information
University/education
16 De Crespigny Park
London
SE5 8AF
England
United Kingdom
| Phone | +44 (0)20 7848 0002 |
|---|---|
| slam-ioppn.research@kcl.ac.uk | |
| Website | http://www.kcl.ac.uk/index.aspx |
"ROR" |
https://ror.org/0220mzb33 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/01/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | It is intended that the results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals. Where appropriate, the results will be disseminated to the general public by means of press releases, posts on social media and at public engagement events. The Consort Guidelines and checklist will be reviewed prior to generating any publications for the trial. Individual participants will not be identifiable in publications. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
04/01/2023: The intention to publish date was changed from 01/01/2023 to 01/01/2024.
01/09/2022: The total final enrolment number has been added.
13/04/2022: The following changes have been made:
1. The ethics approval has been added.
2. The recruitment start date has been changed from 01/02/2022 to 20/04/2022.
3. The recruitment end date has been changed from 01/02/2022 to 01/08/2022.
4. The overall trial end date has been changed from 01/06/2022 to 01/09/2022 and the plain English summary updated accordingly.
5. The participant inclusion criteria have been changed.
6. The participant exclusion criteria have been changed.
7. The intention to publish date has been changed from 01/10/2022 to 01/01/2023.
01/11/2021: The recruitment start date was changed from 01/11/2021 to 01/02/2022.
15/10/2021: The sponsor contact email address has been changed.
30/09/2021: Trial's existence confirmed by King's College London.
