Investigation of the safety, tolerability and pharmacokinetics of Cannabidiol in Healthy Volunteers
A Phase 1, Randomised, Placebo-controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Healthy Volunteers
Victorian State Government
24 participants
Sep 6, 2018
Interventional
Conditions
Summary
This study is a Phase 1, randomised, dose escalation, double-blind, placebo-controlled study of cannabidiol (CBD) in healthy volunteers. The study is designed to evaluate the safety, tolerability and pharmacokinetics (PK) of a single dose of Cannabidiol in healthy volunteers. A total of 24 subjects will be enrolled in this study. Eight subjects in each cohort will be randomised to receive either CBD or placebo in a 3:1 ratio, so that 6 subjects receive CBD and 2 subjects receive placebo: Cohort 1: 5mg/kg Cohort 2: 10mg/kg Cohort 3: 20mg/kg. Sentinel dosing will be implemented in the first 2 subjects (1 CBD and 1 placebo) of Cohort 1; the rest of the subjects in the cohort will then be dosed if there are no significant safety concerns identified in the sentinel participants within at least the first 24 hours after administration of the oral dose (CBD or placebo). Sentinel dosing may be implemented for subsequent cohorts if deemed appropriate by the Safety Review Committee (SRC). The study will be conducted at a single study centre. Each participant will be involved in the study for a maximum of 15 days (screening period (up to 28 days); treatment period (3 days); follow-up visits (Days 4, 6 and 8) and telephone contact (Day 15). The SRC will undertake a dose-escalation review of all available safety data up to Day 8, approximately 2 weeks after the final subject in a cohort has been dosed and prior to subjects commencing the next dose. The primary objective of the study is to: • Assess the safety and tolerability of CBD following a single oral dose in healthy volunteers The secondary objective of the study is to: • Assess the PK of CBD following a single oral dose in healthy volunteers The primary endpoints to be evaluated in the study are: • Safety and tolerability of CBD, including review of: - adverse events - vital signs - 12-lead ECG - clinical laboratory assessments - concomitant medications. The secondary endpoints to be evaluated in the study are: • The PK of CBD, plasma concentration of CBD and PK parameters including: - AUClast – area under the plasma concentration versus time curve from time zero to the last quantifiable concentration - AUCinf – area under the plasma concentration versus time curve extrapolated to infinite time - Cmax – maximum observed plasma concentration - Tmax – time of maximum observed plasma concentration - Kel – apparent terminal elimination rate constant - T1/2 – apparent terminal elimination half-life The CBD to be manufactured for this study will be prepared as an oil for oral administration. Dosing will be based on subject body weight and the assigned dose cohort. The matching placebo will be composed of the same excipients as the study drug (without the CBD).
Eligibility
Inclusion Criteria11
- Male or females aged between 18 - 49 years (inclusive);
- Body mass index between 18 and 30 kg/m2 (inclusive);
- Negative screen for drugs of abuse, alcohol, hepatitis B surface antigen, Hepatitis C Virus and Human Immunodeficiency Virus;
- Negative screen for drugs of abuse and alcohol pre-dose on Day -1;
- Clinical laboratory values within the normal limits as defined by the clinical laboratory, unless the results are deemed as not clinically significant by the investigator
- Be in general good health without clinically significant medical history;
- Ability to provide written informed consent;
- Willing and able to follow study instructions and likely to complete all study requirements;
- Females of childbearing potential must agree to use an established oral, injected or implanted hormonal method of contraception throughout the study (Screening to Day 15) and for 90 days after receiving the study drug.
- Males must agree to use adequate methods of contraception throughout the study (Screening to Day 15) and for 90 days after receiving study drug, excluding sterilized males (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate)
- Suitable venous access.
Exclusion Criteria15
- Positive screening result for cannabis use;
- Current smoker, or a history of regular (more than weekly) use of tobacco- or nicotine-containing products (including e-cigarettes) within 2 months prior to screening; cotinine (nicotine) test to be performed at screening;
- History of excessive alcohol intake (more than four standard drinks daily, on average) or use of recreational drugs within the last 3 months prior to screening;
- Use of prescription or over the counter medications within 7 days of investigational product administration, except for hormonal contraception, simple analgesics such as paracetamol, oral non-steroidal anti-inflammatory drugs and vitamins unless approved by the sponsor medical monitor and study doctor;
- Consumption of grapefruit, grapefruit juice and Seville oranges within 1 week prior to study drug dose or the use of CYP3A inducers/inhibitors within 2 weeks prior to study drug dose, until completion of the study (Day 15 visit). Study doctor will advise what these inducers/inhibitors are..
- Standard donation of blood within 30 days of investigational product administration;
- Participation in any investigational drug study within 30 days prior to screening;
- Females who are pregnant or breastfeeding;
- Clinically significant (as judged by the investigator) presence of acute illness (e.g. gastrointestinal illness, infection such as influenza, upper respiratory tract infection) at admission to the study unit;
- Anticipated need for surgery or hospitalisation during the study;
- History of brady- or tachy-dysrhythmias;
- History of heart failure or heart disease;
- Sensitivity to CBD;
- Allergy to soybeans or any of the excipients in the IP or placebo preparation.
- Any condition, which in the investigator’s opinion, puts the subject at significant risk, could confound the study results or may interfere significantly with the subject’s participation in the study.
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Interventions
A total of 24 healthy volunteers will be enrolled in this study and divided into 3 cohorts. Eight participants in every cohort will receive a single oral dose of either Cannabidiol (CBD) oil or placebo oil, such that 6 participants will receive CBD and 2 will receive placebo. The volume given will be calculated based on the participants weight and Cohort group assigned. The oil will be administered following a minimum of 10 hours of overnight fasting (no food or drink, other than water up to 1 hour before dosing) and 30 minutes after commencing a high fat breakfast. Participants should start the meal 30 minutes prior to CBD/placebo oil administration and complete it at least 5 minutes before dosing. No food is allowed for at least 4 hours post-dose. Water is allowed as desired except for one hour before dosing. Immediately following dosing, 240 mL of water will be provided. The content of the high fat breakfast will follow US FDA/Centre for Drug Evaluation and Research (CDER) Guidance regarding caloric content and composition. An example of a high fat breakfast would be two eggs fried in butter, two strips of bacon, two slices of toast with butter, 4 ounces (approximately 115 g) of hash brown potatoes and 8 ounces (approximately 230 g) of whole milk. Dosing syringes will be capped and weighed pre and post product administration and participants observed during dosing to confirm volume of product delivered. Syringes will be retained until inspected and monitor verified. Three increasing doses of CBD will be investigated: 5mg/kg (Cohort 1), 10mg/kg (Cohort 2) and 20mg/kg (Cohort 3). A Safety Review Commitee will undertake a dose-escalation review of all available safety data up to Day 8 following every cohort, and prior to participants commencing the next dose. Sentinel dosing will be implemented in the first 2 participants (1 CBD and 1 placebo) of Cohort 1. Twenty-four hour safety data will be reviewed and if no significant safety concerns, the remaining 6 participants in the cohort will then be dosed. Sentinel dosing may be implemented for Cohorts 2 and 3 if deemed necessary by the Safety Review Committee.
Locations(1)
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ACTRN12618001424291