Safety and Pharmacokinetics of Cannabidiol in Healthy Volunteers

Inclusion Criteria:

• Ability to provide voluntary, written informed consent

• Males and females, aged 18 to 55 years inclusive at time of informed consent.

• Total body weight ≥50 kg and body mass index (BMI) between 18 and 32 kg/m2inclusive.

• Women of childbearing potential (WOCBP) must have a negative pregnancy test atScreening and Day -1.

• WOCBP must agree to the use a highly effective birth control (refer to Appendix 11.1) from Screening through 30 days following the last dose of study drug.

• Male participants must agree to use highly effective birth control including condom (refer to Appendix 11.1) from Screening through 90 days following the last dose ofstudy drug. Male participants with female partners that are surgically sterile orpost menopausal (defined as being amenorrhoeic for at least 12 months without analternative medical cause), or male participants who have undergone sterilisationand have had testing to confirm the success of the sterilisation, may also beincluded and will not be required to use above-described methods of contraception.Male participants must also agree not to donate sperm up to 90 days following thelast dose of study drug.

• Considered healthy, as determined by medical evaluation by the Investigatorincluding medical history and physical examination.

• Vital signs after 5 minutes resting in supine position within the following ranges:Systolic blood pressure: 90 to 140 mmHg inclusive; Diastolic blood pressure: 40 to 90 mmHg inclusive; Heart rate: 40 to 100 bpm inclusive.

• Standard 12-lead ECG with parameters (average of triplicate readings) after 10minutes in supine position within the following ranges: QRS <120 msec; QT <500 msec;QTc ≤450 msec (both genders); PR interval ≥120 to ≤220 msec.

• Negative tests for HBsAg, HBcAb (if HBsAg positive), anti-HCV, and HIV antibody atScreening (positive anti-HCV antibody allowed if HCV PCR is negative).

• Screening and Day -1 safety laboratory test values within normal ranges. Out ofnormal range values may be accepted by the Investigator if not considered clinicallysignificant, with the exception of the following: ALT or AST >1.5 x upper limit ofnormal (ULN); Total, indirect, or direct bilirubin >1.5 x ULN. Participants withGilbert's syndrome with indirect bilirubin outside of the normal range will beexcluded from the study.

• Willing to refrain from consumption of alcohol as follows: Group A: for at least 48hours prior to Screening, Day -1, and Day 20, and throughout the in-patientconfinement periods and post-dose follow-up visits (consumption of alcohol ispermitted during the outpatient washout period); Group B: for at least 48 hoursprior to Screening and Day -1, and throughout the study.

• Willing to defer blood donations to a blood service for minimum of 30 days followingthe last dose of study drug.

• In the opinion of the Investigator, is willing and able to comply with andunderstand study requirements and be available for the required study visits.

Exclusion Criteria:

• Female participant who is pregnant or breastfeeding, or planning to become pregnantor breastfeed, or planning to donate ova during study participation.

• History or presence of a medical condition that, in the opinion of the Investigator,would interfere with the evaluation of the study drug or lead to increased risk ofharm.

• Presence of any chronic medical condition requiring ongoing treatment.

• Any clinically significant illness, medical/surgical procedure, or trauma within 4weeks prior to Screening, as per Investigator judgement.

• Documented evidence of current or past cardiovascular disease including cardiacarrhythmias or family history of congenital long QT syndrome, Brugada syndrome, orunexplained sudden cardiac death.

• Any gastrointestinal surgery or condition or disease that could affect drugabsorption, distribution, or excretion (e.g., gastrectomy, cholecystectomy,diarrhea, recurrent nausea/vomiting).

• History of malignancy of any organ system (other than localised basal cell carcinomaof the skin or in situ cervical cancer considered treated and cured), treated oruntreated, within 5 years before Screening, regardless of if there is no evidence oflocal recurrence or metastases.

• History of schizophrenia, bipolar disorder psychoses, disorders requiring lithium,attempted or planned suicide, or any other severe (disabling) chronic psychiatricdiagnosis including generalised anxiety and obsessive-compulsive disorders.Hospitalisation within 5 years before Screening due to psychiatric illness or due todanger to self or others.

• Current use (or within the 3 months prior to Screening) of other cannabinoid orcannabis products.

• History of allergy or other adverse reaction to cannabinoid or cannabis products atany time in the past or known or suspected hypersensitivity to any of the componentsof the formulation.

• Current or recent (within 2 months prior to Screening) use of any tobacco ornicotine products (including e-cigarettes, vaping, or dipping) at >5 cigarettes perweek or equivalent. Causal/social smokers (≤5 cigarettes per week or equivalent) arepermitted.

• History of substance abuse disorder(s), as determined by the Investigator, within 5years of Screening, including but not limited to alcohol, illicit drugs, andinappropriate use of prescription drugs.

• Positive urine drug test or alcohol breath test at Screening or Day 1, unless thereis an explanation deemed acceptable by the Investigator and/or the participant testsnegative upon re-test (one re-test permitted per scheduled time point).

• Use of any prescription medicines or marijuana within 14 days of Day -1 or use ofany nonprescription medicines, supplements, or vaccines within 7 days of Day 1.Occasional (PRN) paracetamol (up to 2 g/day) or ibuprofen (up to 1.2 g/day) use maybe permitted, at Investigator discretion. Hormonal contraceptives are permitted.

• Consumption of food and/or beverages containing Seville oranges or Seville orangejuice, or grapefruit or grapefruit juice, or poppy seeds within 7 days prior to Day -1.

• Consumption of caffeine/xanthine products within 24 hours prior to Day -1.

• Use of any investigational drug within 30 days or <5 half-lives, whichever islonger, prior to first dose of study drug.

• Donation or receipt of any blood or blood products at a blood bank or donationcentre within 30 days prior to Screening.

• Identified as a site employee of the Investigator or study centre, with directinvolvement in the proposed study or other studies under the direction of thatInvestigator or study centre, as well as family members (i.e., immediate, husband,wife or de facto and their children, adopted or natural) of the site employees orthe Investigator.