ANZCTR - Registration

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12618001424291

Ethics application status

Approved

Date submitted

2/08/2018

Date registered

27/08/2018

Date last updated

1/08/2019

Date data sharing statement initially provided

1/08/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Investigation of the safety, tolerability and pharmacokinetics of Cannabidiol in Healthy Volunteers

Scientific title

A Phase 1, Randomised, Placebo-controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Healthy Volunteers

Secondary ID [1]

NTA1701

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Severe Intractable Epilepsy

Condition category

Condition code

Neurological

Epilepsy

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

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.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

The placebo oil will be composed of the same excipients as the Cannabidiol oil (without the active ingredient, CBD) and will be identical in appearance to maintain the blind. The volume of oil administered will be based on participant weight and cohort group assigned.

Control group

Placebo

Outcomes

Primary outcome [1]

To determine the safety and tolerability of CBD following a single oral dose in healthy volunteers to support use in patients with severe intractable epilepsy.

This will be measured by evaluating the incidence of adverse events and changes from baseline of relevant parameters including, vital signs, clinical laboratory assessments, 12-lead ECG data and concomitant medications.

Timepoint [1]

Day 15 post-dose

Adverse events will be recorded for study duration, to Day 15 post dose (final visit). All AEs will be followed until resolution, until the condition stabilises, until the event is otherwise explained, or until the subject is lost to follow-up.

Vital signs will be measured Day 1: within 60 minutes prior to dosing, 2 hours, 4 hours, 8 hours and 12 hours post dose; Day 2: 24 hours and 36 hours post dose; Day 3: 48 hours post dose and on Day 8 (168h post dose).

Clinical laboratory samples will be collected and measured on Day -1 and Day 3: 48 hours post dose and Day 8 (168h post dose).

12-Lead ECG's will be undertaken within 60 minutes prior to dosing on Day 1, 4 hours post dose and daily on Day 3 and Day 8 (168h) post dose

Concomitant medication information will be collected throughout the study to Day 15 post-treatment (final visit).

Secondary outcome [1]

To assess the Pharmacokinetics of CBD following a single oral dose in healthy volunteers.

The PK of CBD, plasma concentration of CBD will be evaluated by:
- 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

Timepoint [1]

Day 8 post-dose

Blood samples for PK analysis will be collected Day 1: within 60 minutes prior to dosing, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post dose; Day 2: 24 hours and 36 hours post dose; Day 3: 48 hours post dose, Day 4 (72 hours post dose), Day 6 (120h post dose) and on Day 8 (168h post dose).

Eligibility

Key inclusion criteria

1. Male or females aged between 18 - 49 years (inclusive);
2. Body mass index between 18 and 30 kg/m2 (inclusive);
3. Negative screen for drugs of abuse, alcohol, hepatitis B surface antigen, Hepatitis C Virus and Human Immunodeficiency Virus;
4. Negative screen for drugs of abuse and alcohol pre-dose on Day -1;
5. 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
6. Be in general good health without clinically significant medical history;
7. Ability to provide written informed consent;
8. Willing and able to follow study instructions and likely to complete all study requirements;
9. 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.
10. 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)
11. Suitable venous access.

Minimum age

18 Years

Maximum age

49 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Positive screening result for cannabis use;
2. 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;
3. 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;
4. 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;
5. 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..
6 Standard donation of blood within 30 days of investigational product administration;
7. Participation in any investigational drug study within 30 days prior to screening;
8. Females who are pregnant or breastfeeding;
9. 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;
10. Anticipated need for surgery or hospitalisation during the study;
11. History of brady- or tachy-dysrhythmias;
12. History of heart failure or heart disease;
13. Sensitivity to CBD;
14. Allergy to soybeans or any of the excipients in the IP or placebo preparation.
15. 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.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

This is a double-blind study and thus the investigator, site staff (other than pharmacists), sponsor, sponsors delegates (if applicable) and subjects are all blinded to treatment.

Prior to study start, the unblinded study statistician will generate a treatment assignment list. This list will detail the treatment (CBD or placebo) for every randomised participant and will be provided to the unblinded pharmacist to be stored securely at the pharmacy with access restricted to the unblinded staff only

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

A computer-generated randomisation schedule will be prepared by an unblinded statistician prior to the start of the study

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 1

Type of endpoint/s

Safety

Statistical methods / analysis

All safety data will be summarised using descriptive statistics (mean, median, standard deviation, minimum and maximum) or frequency counts and percentages, as appropriate to the type of data. Presentation of quantitative safety data will include change from baseline, where baseline will be defined as the last available, valid, non-missing assessment prior to dosing.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

5/09/2018

Actual

6/09/2018

Date of last participant enrolment

Anticipated

Actual

12/10/2018

Date of last data collection

Anticipated

Actual

2/11/2018

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Nucleus Network - Melbourne

Recruitment postcode(s) [1]

3004 - Melbourne

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Victorian State Government

Address [1]

Victorian State Government
Department of Health and Human Services
50 Lonsdale Street
Melbourne Victoria 3000
Australia

Country [1]

Australia

Primary sponsor type

Government body

Name

Victorian State Government

Address

Victorian State Government
Department of Health and Human Services
50 Lonsdale Street
Melbourne Victoria 3000
Australia

Country

Australia

Secondary sponsor category [1]

Other

Name [1]

Neuroscience Trials Australia

Address [1]

Melbourne Brain Centre
245 Burgundy Street
Heidelberg VIC 3084

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Ethics Committee (EC00315)

Ethics committee address [1]

55 Commercial Rd, 
Melbourne VIC 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

01/12/2017

Approval date [1]

05/12/2017

Ethics approval number [1]

308/17

Summary

Brief 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).

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Jason Lickliter

Address

Nucleus Network
Level 5 Burnet Building AMREP Precinct
89 Commercial Rd
Melbourne VIC 3004

Country

Australia

Phone

+ 61 3 9076 8960

Fax

+ 613 9076 8911

j.lickliter@nucleusnetwork.com.au

Contact person for public queries

Name

Katherine Ong

Address

Office of Medicinal Cannabis
Department of Health and Human Services
50 Lonsdale Street, Melbourne VIC 3000

Country

Australia

Phone

+ 61 3 9096 1760

Fax

Katherine.Ong@dhhs.vic.gov.au

Contact person for scientific queries

Name

Katherine Ong

Address

Office of Medicinal Cannabis
Department of Health and Human Services
50 Lonsdale Street, Melbourne VIC 3000

Country

Australia

Phone

+ 61 3 9096 1760

Fax

Katherine.Ong@dhhs.vic.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Data will not be shared at this time.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	A Phase 1, Randomised, Placebo-Controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Fed Healthy Volunteers.	2020	https://dx.doi.org/10.1007/s13318-020-00624-6

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Did you know?

Documents added manually

Documents added automatically