Pharmacokinetic Study of a Novel Lipid Formulation of Cannabidiol Compared to a Standard Formulation

Study Overview
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Brief Summary
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Cannabidiol (CBD) has been approved as a treatment for rare childhood epilepsies and could be an effective treatment for psychotic disorders, anxiety disorders and addictions. It is available as an oral liquid and as standard oral capsules. The bioavailability of oral cannabidiol is poor (only around 5-10% is absorbed), particularly in the fasted state. With food, its absorption is much higher. In one study, a high-fat breakfast increased the maximum plasma concentration by 4-5 times. As a result of this food effect, when prescribing standard oral formulations of CBD, clinicians should provide advice on dosing the drug according to mealtimes, otherwise, there may be an increased risk of side effects or limited effectiveness. One way to reduce the food effect and improve bioavailability is to use lipid encapsulation. In the present study, the investigators will evaluate CBD at the dose that is effective in patients with chronic psychosis (1000mg). The novel formulation will use lipids that are all EU pharmacopoeia approved and have been used in medicinal products before. The study aims to assess whether a novel lipid formulation can increase the bioavailability of oral CBD in the fasting state.

Official Title
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Pharmacokinetic Study of a Novel Lipid Formulation of Cannabidiol Compared to a Standard Formulation

Conditions
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Absorption; Chemicals

Intervention / Treatment
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* Drug: Cannabidiol standard formulation
* Drug: Cannabidiol novel formulation


Participation Criteria
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Eligibility Criteria
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Inclusion criteria i. Healthy volunteers. Defined as healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine. ii. Age 18-45 iii. Agreeing to fast 15 hours; 10pm-1pm on dosing days iv. Capable of giving informed consent v. Written informed consent from participant Exclusion criteria i. 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. ii. 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. iii. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any neurological or mental illness. iv. Surgery or medical condition that might affect absorption of medicines. v. Blood pressure and heart rate in supine position at the screening examination outside the ranges: blood pressure 90-140 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 40-100 beats/min. 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. vi. Loss of more than 400 mL blood during the 3 months before the trial, e.g. as a blood donor. vii. Any prescribed medication (apart from contraceptives) viii. Use of any CBD products within six months of IMP administration ix. Use of any over-the-counter medications or health supplements within the past 2 weeks x. BMI <18 or >30.0kg/m2 xi. History of alcohol or substance misuse disorder xii. Intake of more than 14 units of alcohol weekly. xiii. Smokes more than 10 cigarettes per day xiv. Use of any illicit substances within the last six months of IMP administration xv. Pregnant or breastfeeding xvi. 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. xvii. eGFR≤ 70 mls/min xviii. Any liver function or renal function test abnormality. A repeat is allowed on one occasion for determination of eligibility. xix. Urine drug screen positive for any substances xx. Positive alcohol breath test xxi. Participant in any other clinical trial or experimental drug study in the past 3 months xxii. Known hypersensitivity to CBD and/or SEEK formulation excipients xxiii. Participant is not able to swallow capsules

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Novel lipid formulation cannabidiol<br> | Drug: Cannabidiol novel formulation<br>* Cannabidiol 1000mg with lipid encapsulation, single dose, oral<br>|
| Active Comparator: Standard formulation cannabidiol<br> | Drug: Cannabidiol standard formulation<br>* Cannabidiol 1000mg standard formulation, single dose, oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total drug exposure. (Area under the curve to infinity [AUC(inf)] | Difference in AUC(inf) for a single dose of oral CBD between the novel and standard formulations in the fasting state. | 0 - 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum plasma concentration | 0 - 48 hours | 
| Tmax | Time after administration of drug when maximum plasma concentration is reached | 0 - 48 hours | 
| Plasma half-life (t½) |  | 0 - 48 hours | 
| 48 hour drug exposure (AUC0-48) | Area under the concentration-time curve from time zero to 48hours | 0 - 48 hours | 
| Drug Effects Questionnaire (DEQ-5) | The DEQ-5 is questionnaire with five items, for example ''Do you feel a drug effect, right now?' with the response anchors 'Not at all' and 'Extremely'. | pre dose and at 1, 2, 4, 8, 24 and 48hrs post-dose. | 
| Gastrointestinal Symptom Rating Scale (GSRS) | The GSRS is a 15-item rating scale which assesses five symptom clusters: reflux, abdominal pain, indigestion, diarrhoea and constipation. Each item is assessed with a 7-point Likert scale. The standard recall period for the scale is 7 days; this will be amended so that it assesses past 24 hours only. | The scale will be used pre-dose and at 24 and 48 hours post dose. |