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

NCT05032807 | Completed Phase 1 Results

• 1 other identifier: IRAS: 288415
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Absorption; Chemicals

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Cmax

  0 - 48 hours

• Tmax

  0 - 48 hours

• Plasma Half-life (t½)

  0 - 48 hours

• 48 Hour Drug Exposure (AUC0-48)

  0 - 48 hours

• Gastrointestinal Symptom Rating Scale (GSRS) - Total Score

  The scale will be used pre-dose and at 24 and 48 hours post dose.

Study Arms (2)

Novel lipid formulation then standard formulation

EXPERIMENTAL

Drug: Standard formulation; Drug: Novel formulation

Standard formulation then lipid formulation

EXPERIMENTAL

Drug: Standard formulation; Drug: Novel formulation

Interventions

Standard formulation DRUG

Cannabidiol 1000mg standard formulation, single dose, oral

Novel lipid formulation then standard formulation; Standard formulation then lipid formulation

Novel formulation DRUG

Cannabidiol 1000mg with lipid matrix, single dose, oral

Novel lipid formulation then standard formulation; Standard formulation then lipid formulation

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• King's College London: lead

Study Sites (1)

King's College London

London, SE5 8AB, United Kingdom

Location

Related Publications (1)

• Chesney E, Mazibuko N, Oliver D, Minichino A, Lamper AD, Chester L, Reilly TJ, Lloyd M, Krakstrom M, Dickens AM, Oresic M, Lynch E, Stoloff G, Mehta MA, McGuire P. Novel Lipid Formulation Increases Absorption of Oral Cannabidiol (CBD). Pharmaceutics. 2024 Dec 1;16(12):1537. doi: 10.3390/pharmaceutics16121537.

  PMID: 39771516 DERIVED

Limitations and Caveats

Halflife and AUCinf could not be calculated for all participants in the standard CBD arm as plasma levels were not falling at the final time point.

Results Point of Contact

• Title: Dr Edward Chesney
• Organization: King's College London

edward.chesney@kcl.ac.uk

+44 (0)20 7848 0728

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: September 2, 2021
• Study Start: July 1, 2022
• Primary Completion: August 26, 2022
• Study Completion: September 10, 2022
• Last Updated: February 6, 2024
• Results First Posted: February 6, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)