Pharmacokinetic Study of a Novel Lipid Formulation of Cannabidiol Compared to a Standard Formulation
Condition: Absorption; Chemicals
Intervention: Standard formulation; Novel formulation
Intervention description: Cannabidiol 1000mg standard formulation, single dose, oral; Cannabidiol 1000mg with lipid matrix, single dose, oral
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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 excipients. 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.
    

Eligibility criteria:

        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