CompletedPhase 1ACTRN12621001181897

A phase I study to measure the absorption of cannabidiol (CBD) in healthy volunteers after consumption of an oral CBD soft-gel capsule

A Phase I, open label, randomised, single dose, two-way crossover study in healthy volunteers to determine the pharmacokinetics of two doses of an oral cannabidiol soft-gel capsule.

Sponsor

Avecho Biotechnology

Enrollment

16 participants

Start Date

Sep 7, 2021

Study Type

Interventional

Conditions

Insomnia

Summary

Cannabidiol is a phytocannabinoid found naturally in the Cannabis sativa plant. Despite CBD’s long history of use, its medicinal properties have been somewhat anecdotal. There are very few pharmaceutically approved products on market, and these are limited to rare clinical indications (i.e. Epidiolex® for rare childhood epilepsy). Cannabidiol is being developed for a range of medicinal applications. These applications typically require CBD at high purity, which can be extracted and purified from Cannabis sativa, or synthetically manufactured. High purity CBD is a white to pale yellow crystalline solid that is insoluble in water. Consequently, CBD is usually administered in an oil vehicle. The limited aqueous solubility of CBD leads to poor oral bioavailability, which has been reported as between 3-8%. CBD has been selected for clinical development in a formulation containing TPM. It is believed that CBD TPM formulations may have improved bioavailability when compared to CBD alone, which would allow for lower doses administered to patients, or the targeting of therapeutic indications that would ordinarily need CBD doses that are so large as to be prohibitive. The proposed Phase I clinical study will evaluate the PK, safety and tolerability of an oral CBD soft-gel capsule. The PK profile of the capsule will be compared at two separate doses. Results from this study will support further clinical development of the CBD soft-gel product, with a focus on indications that can be treated with low-dose CBD.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 55 Yearss

Inclusion Criteria9

Aged greater than or equal to 18 years and less than or equal to 55 years (inclusive).
Participant is free from clinically significant (in the opinion of the Investigator) illness or disease as determined by their medical and surgical history, physical examination, 12-lead ECG, vital signs and clinical laboratory determinations.
Body Mass Index (BMI) greater than or equal to 18.0 and less than or equal to 27 kg/m2 at Screening.
Weight > 50.0 kg at Screening.
Adequate venous access in both arms for collection of a number of blood samples.
Capable of understanding the purposes and risks of the study and able to provide written informed consent before any study-specific screening procedures are performed.
Willing and able to adhere to all protocol requirements.
Female participants must be abstinent or agree to use effective contraception (i.e., pill, condom) during the study period (from the time of first check in until completion of the final study visit).
Male participants that are not surgically sterile (i.e. vasectomy) must be abstinent or agree to use effective barrier contraception (i.e., condom) during the study period (from the time of first check in until completion of the final study visit).

Exclusion Criteria25

History of coronary disease, peripheral vascular disease, cerebrovascular accident, transient ischaemic attack, uncontrolled hypertension or signs/symptoms of ischaemic heart disease.
Have a rested systolic blood pressure of < 90 mmHg or > 160 mmHg and/or diastolic blood pressure of < 50 mmHg or > 95 mmHg or radial pulse rate at rest of < 45 beats per minute (bpm) or > 100 bpm at Screening or Check-In (Day -1). Blood Pressure (BP) or heart rate may be re-tested two times in the rested position at intervals of five minutes. The elevation is considered sustained if any values are outside the stated limits after three assessments or judged as clinically significant by the Investigator and the participant may not be enrolled.
History of acute or severe bronchial asthma (excluding childhood or exercise induced asthma), diagnosed obstructive sleep apnoea, hypoxia, hypoxaemia, hypercarbia, or other obstructive airway disease or any condition that may increase the risk for respiratory depression.
History of neurologic conditions such as seizures or convulsive disorders (including epilepsy), severe head injury or increased intracranial pressure.
Presence of current psychiatric condition or psychiatric condition requiring pharmacological management within the last two years.
A calculated creatinine clearance of < 85 mL/minute at Screening or Check-In (Day -1) according to the equation using Cockcroft and Gault.
Liver function tests showing values for ALT or AST > 1.5 times ULN at Screening
Evidence or history of clinically significant (in the opinion of the Investigator) other cardiovascular, pulmonary, neurologic or renal disorders or hepatic, gastrointestinal, oral (difficulty swallowing / taking oral medication), haematological, endocrine, or psychiatric impairment/disorders.
Have undergone surgery requiring, or have received (for any reason) anaesthetic within 30 days of Day 1.
Use of CNS depressants including: opioids, sedative, anxiolytics, hypnotics, neuroleptics, phenothiazines, tranquillisers, skeletal muscle relaxants, sedating antihistamines or cimetidine within 30 days of Day 1.
Use of macrolide antibiotics (e.g., Erythromycin), azole antifungal agents (e.g., Ketoconazole) or protease inhibitors (e.g., Ritonavir) within 30 days of Day 1.
Use of any prescription medication within 14 days of Day 1 and for duration of study, unless approved by both the Investigator and the Medical Monitor (in writing). If necessary, paracetamol (acetaminophen) or ondansetron (or other 5-HT3 receptor antagonist) may be administered with the approval of the Investigator.
Use of any over the counter product, herbal product, diet aid, or hormone supplement, with a particular regard to hemp or products containing cannabidiol, within 14 days of Day 1 and for duration of study, unless approved by both the Investigator and Medical Monitor (in writing).
Known intolerance, allergy or hypersensitivity reactions to medicinal cannabis.
Positive screening test for Human Immunodeficiency Virus (HIV) antibodies, Hepatitis B surface antigen or Hepatitis C antibody.
Evidence or history of substance or alcohol abuse (drink more than 4 standard units of alcohol per day or >10 standard units per week), including positive results for the urine drugs of abuse test or a positive alcohol breath test at Screening or at Check-In (Day -1).
Unwilling or unable to abstain from recreational drug/substance use, alcohol, from check-in until discharge.
Unwilling or unable to abstain from caffeine or other xanthine-containing products from check-in until discharge in each study period.
Participants who are not willing to refrain from smoking 48 hours before check-in until discharge in each study period.
Consumption of grapefruit, grapefruit juice or any products containing CYP3A4 inhibitors and inducers within 14 days of Day 1 and through to completion of the study.
Any known contraindication to blood sampling.
Currently participating in another clinical study involving another IP or extensive blood sampling, or recent study participation ending within 3 months of Day 1.
Donation or loss of more than 500 mL of blood within 3 months of Day 1 and/or not willing to refrain from donating blood/extensive blood sampling for 12 weeks after study completion.
Participants that have or are planning to discontinue effective contraceptive precautions during the study period.
Any issues that, in the opinion of the Investigator, would render the participant unsuitable for study participation.

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Interventions

Treatment A and Treatment B will be ingested in clinic under monitoring from trial staff. Treatment A: Single soft-gel capsule containing oil based formulation with 75 mg cannabidiol and 75 mg to

Treatment A and Treatment B will be ingested in clinic under monitoring from trial staff. Treatment A: Single soft-gel capsule containing oil based formulation with 75 mg cannabidiol and 75 mg tocopheryl phosphate mix (TPM). Treatment B: Two soft-gel capsules containing oil based formulation with a total of 150 mg cannabidiol (2 x 75 mg) and 150 mg (2 x 75 mg) tocopheryl phosphate mix (TPM). Treatment A and Treatment B will be separated by a minimum of 7 days.