RecruitingPhase 1ACTRN12619000443190

A study to evaluate the effect of food on the pharmakokinetics and cardiac function in male and female healthy volunteers who have been administered cannibidiol.

A double-blind, randomized, two-period, two treatment, fixed sequence, crossover (fed versus fasted) study to evaluate the effect of food on pharmacokinetics of CBD with robust ECG monitoring in Healthy Volunteers (HVs)

Sponsor

Kalytera Australia Pty Ltd

Enrollment

32 participants

Start Date

Mar 12, 2019

Study Type

Interventional

Conditions

Acute Graft Versus Host Disease

Summary

This research project is being conducted to investigate the safety and tolerability of multiple doses of cannabidiol (CBD) when administered to healthy volunteers.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 60 Yearss

Inclusion Criteria18

Healthy adult subjects =18 – 60 years of age
Body Mass Index (BMI) of 18 to 30 kg/m2 inclusive and a minimum weight of at least 50 kg at screening and not more than 100 kg at screening
Non-users of tobacco or nicotine-containing products (minimum of 4 weeks from admission)
Subjects with reproductive potential required to practice abstinence or be using and willing to continue using a medically acceptable form of birth control for at least one month prior to screening (at least 3 months for oral contraceptives) and for at least 60 days after the last study drug administration.
Free from any clinically significant abnormality based on medical history, vital signs, physical examination, ECG, and laboratory evaluation at screening and admission to the treatment session, as judged by the investigator or designee.
Systolic blood pressure between 90 to 140 mmHg and diastolic blood pressure between 50 and 90 mmHg at screening and admission to the treatment session.
Male Participants who agree to the following during their participation in this study and for at least 1 month after the last dose of study intervention: Refrain from donating sperm PLUS either:
o Be abstinent from heterosexual [or homosexual] intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below:
o Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) when having sexual intercourse with a woman of childbearing potential who is not currently pregnant
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
o Is not a woman of childbearing potential (WOCBP) OR
o Is able to abstain from heterosexual intercourse if it is in keeping with her preferred and usual lifestyle (such as participants with same-sex partners)
OR
o Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), during the intervention period and for at least 30 days plus 30 days (a menstrual cycle) after the last dose of study intervention [and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period.]. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
o A WOCBP must have a negative pregnancy test [ serum] as required by local regulations) within [24 hours] before the first dose of study intervention.
Subjects must be able to speak, read and understand English sufficiently to understand the nature of the study and provide written informed consent
Subjects must be capable of giving signed informed consent and agree to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Subjects must have understood and provided written informed consent prior to initiation of any protocol-specific procedures.

Exclusion Criteria34

History of clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal or other major disease as determined by the Investigator and/or Sponsor’s Medical Monitor
Evidence of disease that may influence the outcome of the study within 4 weeks before dosing as determined by the Investigator and/or Sponsor’s Medical Monitor
Any history of gastrointestinal surgery that may affect the pharmacokinetic profile of the study drug
Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG findings or laboratory test results that requires medical treatment at Screening or Baseline
History of any medical condition which, in the opinion of the Investigator, may interfere with study procedures or compromise subject safety (e.g. psychiatric illness, disability or social situation)
Known history of clinically significant drug allergy (including to study drugs or any of their excipients) at Screening or Baseline
Known history of clinically significant food allergies or presently experiencing significant seasonal or perennial allergy at Screening or Baseline
Active viral hepatitis (B or C) and HIV as demonstrated by positive serology at Screening
Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
Alanine transaminase (ALT) >1.5x upper limit of normal (ULD)
Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if fractionated and direct bilirubin <35%)
Persistent systolic blood pressure (BP) > 140 mmHg or < 90 mmHg and diastolic BP >90mmHg or <40mmHg at Screening or Baseline
Heart rate <50 or >100 beats/minute at Screening
History of prolonged QT/QTc interval
A history of risk factors for torsade de pointes or the use of concomitant medications that prolong the QT/QTc interval
Corrected QT interval (QTc) >450 milliseconds (msec) (for males) or >470 msec (for females)
The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine-read or manually over-read
The specific formula that will be used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual participant and then the lowest QTc value used to include or discontinue the participant from the trial.
For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used
A history of additional risk factors for TdP (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)
History of myocardial infarction or active ischemic heart disease
History of clinically significant arrhythmia or uncontrolled arrhythmia
Intake of caffeinated beverages or food within 72 hours before dosing
Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug metabolizing enzymes and transporters (e.g. grapefruit, grapefruit juice, apple or orange juice, vegetables from the mustard green family) within 1 week before dosing. Alcohol within 72 hours of dosing.
Intake of herbal preparations containing St. John’s Wort within 4 weeks before dosing
Past or intended use of over-the-counter (OTC) or prescription medications 2 weeks before first dosing unless agreed by the Investigator and Sponsor’s Medical Monitor to not be clinically relevant
Live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study
Regular alcohol consumption within 3 months prior to the study defined as:
An average weekly intake of >14 units for males and females. One unit is equivalent to 8g of alcohol: pot of beer (~240mL), 1 glass (125mL) of wine or 1 (25mL) measure of spirits
History of drug or alcohol dependency or abuse within the 2 years before Screening, or who have a positive urine drug or alcohol test at Screening or Baseline
Engagement in strenuous exercise within 72 hours before dosing
Subject is a female who is pregnant, nursing, or breastfeeding, or who intends to become pregnant during the participation in the study.
Currently enrolled in another clinical trial or used any investigational drug or device within 30 days preceding informed consent
A subject who, in the opinion of the investigator or designee, is not considered to be suitable and is unlikely to comply with the study protocol for any reason.

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Interventions

A double-blind, randomized, two-period, two treatment, fixed sequence, crossover (fed versus fasted) study. The Cannabidiol (CBD) and placebo will be administered orally as a liquid solution accord

A double-blind, randomized, two-period, two treatment, fixed sequence, crossover (fed versus fasted) study. The Cannabidiol (CBD) and placebo will be administered orally as a liquid solution according to the pre-determined randomization scheme. The final administration volume for all CBD doses and placebo will be supplied as 6mL/vial (fill volume), where the deliverable volume is 5mL, wherein 4 vials will constitute one dose of either 600mg CBD or 1200mg CBD or placebo Screening: Days -28 to -2 Fasted Period Randomization: Days -1 or 1 PK sampling & Holter monitoring/Single Dose Administration: Days 1, 9 and 15 1st Washout: Days 2-8 Multiple Dosing (two times per day): Days 10 to 15 2nd Washout: Days 16 to 29 Fed Period - Subjects crossover to fed period (during Fed period subjects will receive a high calorie meal in the morning, 30 minutes prior to administration of the Investigational Medicinal Product (IMP) Pharmacokinetic (PK) sampling & Holter monitoring/Single Dose Administration: Days 30, 38 and 44 3rd Washout: Days 31 to 37 Multiple Dosing Administration (two times a day): Days 38-44 End of Study: Day 45 Safety Follow Up: Day 51 (phone call) Fasted state: Beginning on Day 1 with a single dose administration. A 7-day washout period will follow. On Days 9 and 15 subjects will be administered the total daily dose (i.e. 600mg, 1200mg or placebo) as a single morning dose after being fasted for a minimum of 10 hours. On Days 10-14 subjects will be administered IMP or placebo twice-daily (BID) with the first daily dose administered post a minimum of 10 hour fast. At least 8 hours should lapse between multiple daily doses (±2 hours). The second daily dose should be administered post a minimum 2-hour fast.14-day washout period will commence post Day 15. Fed state: On day 30 subjects will be administered a high calorie/high fat meal 30 minutes prior to receiving a single dose of CBD or placebo. This will be followed by a 7-day washout period. On day 38 subjects will receive a high calorie/high fat meal 30 minutes prior to Cannabidiol (CBD) or placebo dosing. On Days 30 and 38 subjects will receive a single morning dose of IMP or placebo (i.e. 600mg, 1200mg or placebo) 30 minutes after starting the consumption of a high calorie/high fat meal. and continue on this meal and dosing regimen for 7 days (until day 44). The Phase 1 unit will provide subjects with written email/text reminders of fasting requirements and periods. This is also well documented in the participant information and consent form.