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Trial registered on ANZCTR


Registration number
ACTRN12619001013156
Ethics application status
Approved
Date submitted
27/06/2019
Date registered
15/07/2019
Date last updated
2/03/2021
Date data sharing statement initially provided
15/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the safety, tolerability, and pharmacokinetics of a medicinal cannabinoid oil formulation in chronic non-cancer pain participants on long term opioid treatments
Scientific title
An open label study to evaluate the safety, tolerability, and pharmacokinetics of a medicinal cannabinoid oil formulation in chronic non-cancer pain patients
Secondary ID [1] 298613 0
Nil known
Universal Trial Number (UTN)
U1111-1236-0524
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic pain 313470 0
Condition category
Condition code
Anaesthesiology 311899 311899 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is an open label dose-escalation pharmacokinetic study which will evaluate the safety and tolerability of an oral cannabinoid (THC:CBD) oil formulation following a single dose and following repeated dosing in patients with chronic non-cancer pain. The study will consist of 5 stages:
Stage 1: A single dose of 2.5mg THC/2.5mg CBD
Stage 2: A single dose of 2.5mg THC/2.5mg CBD following a high-fat meal and then a total daily dose of 5mg THC/5mg CBD (twice per day) for a week
Stage 3: A single dose of 5mg THC/5mg CBD followed by a total daily dose of 10mg THC/10mg CBD (twice per day) for a week
Stage 4: A single dose of 7.5mg THC/7.5mg CBD followed by a total daily dose of 15mg THC/15mg CBD (twice per day) for a week
Stage 5: A single dose of 12.5mg THC/12.5mg CBD

In Stage 1, participants will receive a single dose of 2.5mg THC/2.5mg CBD and bloods will be taken for pharmacokinetic (PK) analysis, after which there will be a 7 day washout period.

In Stage 2, participants will receive a single dose of 2.5mg THC/2.5mg CBD immediately following a high fat meal and bloods will be taken for PK analysis. Participants then continue to take 2.5mg THC/2.5mg CBD twice per dose (total daily dose of 5mg THC/5mg CBD) for one week. The high fat breakfast will be consistent with the Food and Drug Administration guidelines for fat and calorific content and will be consumed 30minutes before consumption of the cannabis oil.

In Stage 3, participants will receive a single dose of 5mg THC/5mg CBD and bloods will be taken for PK analysis. Participants then continue to take 5mg THC/5mg CBD twice per day (total daily dose of 10mg THC/10mg CBD) for one week.

In Stage 4, participants will receive a single dose of 7.5mg THC/7.5mg CBD and bloods will be taken for PK analysis. Participants then continue to take 7.5mg THC/7.5mg CBD twice per day (total daily dose of 15mg THC/15mg CBD) for one week.

In Stage 5, participants will receive a single dose of 12.5mg THC/12.5mg CBD and bloods will be taken for PK analysis. Participants then have a 7 day washout period before returning for the close-out examination.

All participants will progress through the five stages. The total time taken to complete all stages is 36 days. The cannabinoid (THC:CBD) oil formulation will be orally delivered using an oral syringe.

Adherence to the self-dosing schedule will be monitored by having participants return all (used and unused) oral syringes at each site visit.

Three participants will be selected to wear an Actigraph activity monitoring wrist watch commencing on day 2 of the study. The activity monitoring watch will be continuously worn by the participant for the duration of the trail.
Intervention code [1] 314872 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320564 0
Safety of a THC:CBD formulation following a single oral dose and following repeated doses.
Safety will be assessed using a composite of measures:
1. Adverse events (AEs) will be coded and presented using MedDRA. The overall incidence, the incidence of related as well as the incidence of serious adverse events (SAEs) will be summarized per dose and by body system in tables.
2. Vital signs (supine blood pressure, heart rate, body temperature and respiratory rate) collected during weekly clinical assessments: Descriptive statistics (n, mean, standard deviation, median, minimum, and maximum) will be provided for blood pressure, heart rate, body temperature and respiratory rate and for changes from baseline
Timepoint [1] 320564 0
Weekly, at each dose escalation visit and at day 36 post-enrolment.
Primary outcome [2] 320565 0
Local tolerability (assessed by a persons ability to orally swallow the investigational product) will be presented by overall incidence by treatment group per symptom.
Timepoint [2] 320565 0
Assessed at each dose escalation
Secondary outcome [1] 372034 0
Pharmacokinetic profile following a single dose and following repeated doses will be assessed from plasma samples and descriptive statistics (n, mean, standard deviation, median, minimum, and maximum, plus Geometric mean and CV for Cmax and AUC are the derived parameters) provided.
Evaluations of dose-proportionality and effects of multiple dosing will be performed.
Timepoint [1] 372034 0
At each dose escalation
Secondary outcome [2] 372035 0
Pharmacokinetic profile following a high fat meal and a single dose will be assessed from plasma samples and descriptive statistics (n, mean, standard deviation, median, minimum, and maximum, plus Geometric mean and CV for Cmax and AUC are the derived parameters) provided and compared to those of a fasted state.
Timepoint [2] 372035 0
Stage 2 at 30min, 1hr, 2hr, 4hr and 8hrs post dose
Secondary outcome [3] 372036 0
To monitor the effect parameter of pain using the Brief Pain Inventory (BPI). Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) and change from baseline (n, mean, standard deviation, median, minimum and maximum) will be provided.
Timepoint [3] 372036 0
Baseline, at each dose escalation timepoint (days 1, 8, 22, and 29) and at 7 days post last dose (day 36).
Secondary outcome [4] 372257 0
To assess the practicality of actigraphy studies in this cohort. This will be measured by assessing: 1) whether the actigraphy activity watches are returned at the end of the trail and 2) was data collected that was of high enough quality, as determined by the investigator.
Timepoint [4] 372257 0
7 days post the last dose (day 36)
Secondary outcome [5] 372419 0
To monitor the effect parameter of mood using the Depression, Anxiety and Stress Scale (DASS). Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) and change from baseline (n, mean, standard deviation, median, minimum and maximum) will be provided.
Timepoint [5] 372419 0
Baseline, at each dose escalation timepoint (days 1, 8, 22, and 29) and at 7 days post last dose (day 36).
Secondary outcome [6] 372420 0
To monitor the effect parameter of sleep using the Insomnia Severity Index (ISI) and sleep diaries. Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) and change from baseline (n, mean, standard deviation, median, minimum and maximum) will be provided.
Timepoint [6] 372420 0
Baseline, at each dose escalation timepoint (days 1, 8, 22, and 29) and at 7 days post last dose (day 36).
Secondary outcome [7] 372421 0
To monitor the effect parameter of opioid use using self-reported opioid medication reporting. Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) and change from baseline (n, mean, standard deviation, median, minimum and maximum) will be provided.
Timepoint [7] 372421 0
Baseline, at each dose escalation timepoint (days 1, 8, 22, and 29) and at 7 days post last dose (day 36).

Eligibility
Key inclusion criteria
Chronic non-cancer pain on long term treatment (>12months) with high dose (OMEDD >60mg) opioid analgesia.
Willing to cease driving a motor vehicle for the duration of the study.
No cannabis use in the last month.
Minimum age
25 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Dependence on cannabis.
Cardiovascular disorder, epilepsy, psychosis, bipolar disorder, 1st degree relative with psychosis.
Dependence on alcohol, benzodiazepines, or amphetamine type stimulants.
Evidence of severe hepatic/renal impairment.
Active malignancy.
Females who are pregnant, lactating or not using adequate contraception.
Males who are not using adequate contraception.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Adverse events will be summarized by number of participants and percentage of participants by dose escalation.
Pharmacokinetic parameters will be listed and summarised by dose escalation.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/07/2019
Actual
17/10/2019
Date of last participant enrolment
Anticipated
29/02/2020
Actual
5/03/2020
Date of last data collection
Anticipated
4/04/2020
Actual
9/04/2020
Sample size
Target
9
Accrual to date
Final
9
Recruitment in Australia
Recruitment state(s)
WA,VIC
Recruitment hospital [1] 14114 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 15581 0
Emerald Clinics Ltd - West Leederville - West Leederville
Recruitment postcode(s) [1] 26907 0
3065 - Fitzroy
Recruitment postcode(s) [2] 28965 0
6007 - West Leederville

Funding & Sponsors
Funding source category [1] 303155 0
Commercial sector/Industry
Name [1] 303155 0
Zelda Therapeutics
Country [1] 303155 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zelda Therapeutics
Address
Level 26, 140 St Georges Terrace
Perth WA 6000
Country
Australia
Secondary sponsor category [1] 303152 0
None
Name [1] 303152 0
Address [1] 303152 0
Country [1] 303152 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303714 0
St Vincent's Hospital Melbourne Human Research Ethics Committee (EC00343)
Ethics committee address [1] 303714 0
Ethics committee country [1] 303714 0
Australia
Date submitted for ethics approval [1] 303714 0
03/04/2019
Approval date [1] 303714 0
11/06/2019
Ethics approval number [1] 303714 0
53171

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94550 0
A/Prof Yvonne Bonomo
Address 94550 0
Department of Addiction Medicine
St Vincent's Hospital Melbourne
PO Box 2900 Fitzroy VIC 3065
Country 94550 0
Australia
Phone 94550 0
+61 -03-92312627
Fax 94550 0
Email 94550 0
yvonne.bonomo@svha.org.au
Contact person for public queries
Name 94551 0
Amanda Norman
Address 94551 0
Department of Addiction Medicine
St Vincent's Hospital Melbourne
PO Box 2900 Fitzroy VIC 3065
Country 94551 0
Australia
Phone 94551 0
+61-03-92312627
Fax 94551 0
Email 94551 0
amand.norman@svha.org.au
Contact person for scientific queries
Name 94552 0
Yvonne Bonomo
Address 94552 0
Department of Addiction Medicine
St Vincent's Hospital Melbourne
PO Box 2900 Fitzroy VIC 3065
Country 94552 0
Australia
Phone 94552 0
+61 -03-92312627
Fax 94552 0
Email 94552 0
yvonne.bonomo@svha.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Given the small sample size the risk of being able to identify participants is too high.


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
No additional documents have been identified.