Clinical Trial Results:
A phase IIa/b, randomised, double-blind, placebo-controlled, single-site, parallel group clinical trial to examine cannabidiol (CBD) as a pharmacological treatment for cannabis dependence in a young cannabis dependent population.
Summary
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EudraCT number |
2013-000361-36 |
Trial protocol |
GB |
Global end of trial date |
05 Jun 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Jun 2019
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First version publication date |
16 Jun 2019
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Other versions |
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Summary report(s) |
EudraCTupload |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
12/0278
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Joint Research Office
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Sponsor organisation address |
1st Floor Maple House (Suite A) 149 Tottenham Court Road, London, United Kingdom, W1T 7DN
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Public contact |
Samim Patel, Joint Research Office, UCL, +44 0207 679 9320 , samim.patel@ucl.ac.uk
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Scientific contact |
Samim Patel, Joint Research Office, UCL, +44 0207 679 9320 , samim.patel@ucl.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Feb 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Feb 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Jun 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
What is the most effective dose of cannabidiol for reducing cannabis use, and is this dose effective as a treatment for cannabis dependence?
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Protection of trial subjects |
The risk of the IMP is minimal and it has been used in humans previously for up to 18 weeks, and with doses of up to 1500mg with no serious side effects. The maximum daily dose and the duration of the trial (800mg for 4 weeks) is the same as a study carried out in a schizophrenic population. All adverse events will be recorded. If the investigator suspects that the subjects’ disease has progressed faster due to the administration of the IMP, then she/he will record and report this as an unexpected adverse event.
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Background therapy |
All subjects (across each of the treatment conditions) are given motivational interviewing to help them stop using cannabis, which can be harmful to their health. | ||
Evidence for comparator |
CBD has been found to (a) reduce the effects of drug cues - which play a key role in addiction relapse - in cannabis, tobacco and opiate users; (b) offset the harmful effects of THC and brain and behaviour; (c) reduce cigarette smoking. | ||
Actual start date of recruitment |
31 Mar 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 82
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Worldwide total number of subjects |
82
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EEA total number of subjects |
82
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
82
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Community based recruitment within the UK | |||||||||||||||||||||||||
Pre-assignment
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Screening details |
Screening at telephone interview and screening visit for eligibility | |||||||||||||||||||||||||
Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | |||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Twice daily oral dose
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Investigational medicinal product name |
Cannabidiol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Twice daily oral dose
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Arm title
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200mg CBD | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Cannabidiol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Oral twice daily
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Arm title
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400mg CBD | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Cannabidiol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Oral twice daily
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Arm title
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800mg CBD | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Cannabidiol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Oral twice daily
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
200mg CBD
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
400mg CBD
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
800mg CBD
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
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Reporting group title |
200mg CBD
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Reporting group description |
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Reporting group title |
400mg CBD
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Reporting group description |
- | ||
Reporting group title |
800mg CBD
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Reporting group description |
- |
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End point title |
Lower urinary THC-COOH:creatinine compared to placebo (stage 1) | ||||||||||||||||||||
End point description |
Aim: to identify the Most Effective Dose of CBD for reducing cannabis use compared to placebo (MED). A Bayesian model computed the predictive distribution of the outcome, given the evidence available up to that point (weeks 1, 2, 3 and 4). Based on these distributions, for each dose the probability that it is the MED is evidenced by a probability exceeding the pre-specified threshold (Pu) of 0.9; the pre-specified threshold for an ineffective dose (Pl) was 0.1.
In this adaptive Bayesian trial, randomisation occurred in two stages. Stage 1 included 200mg CBD, 400mg CBD, 800mg CBD as well as placebo.
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End point type |
Primary
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End point timeframe |
During treatment weeks (1-4)
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Statistical analysis title |
Co-primary endpoint 1 (stage 1) | ||||||||||||||||||||
Statistical analysis description |
In this adaptive Bayesian trial, randomisation occurred in two stages. Stage 1 included 200mg CBD, 400mg CBD, 800mg CBD as well as placebo
Co-primary endpoint 1 (stage 1): lower urinary THC-COOH:creatinine compared to placebo: 200mg CBD P=0.4191; 400mg CBD P=0.9827; 800mg CBD P=0.9488
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Comparison groups |
Placebo v 200mg CBD v 400mg CBD v 800mg CBD
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Number of subjects included in analysis |
48
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||||||||||
P-value |
> 0.9 [2] | ||||||||||||||||||||
Method |
Bayesian model | ||||||||||||||||||||
Confidence interval |
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Notes [1] - Aim: to identify the Most Effective Dose of CBD for reducing cannabis use compared to placebo (MED). A Bayesian model computed the predictive distribution of the outcome, given the evidence available up to that point (weeks 1, 2, 3 and 4). Based on these distributions, for each dose the probability that it is the MED is evidenced by a probability exceeding the pre-specified threshold (Pu) of 0.9; the pre-specified threshold for an ineffective dose (Pl) was 0.1. [2] - Co-primary endpoint 1 (stage 1): lower urinary THC-COOH:creatinine compared to placebo: 200mg CBD P=0.4191; 400mg CBD P=0.9827; 800mg CBD P=0.9488 |
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End point title |
More self-reported days abstinent compared to placebo (stage 1) | ||||||||||||||||||||
End point description |
Aim: to identify the Most Effective Dose of CBD for reducing cannabis use compared to placebo (MED). A Bayesian model computed the predictive distribution of the outcome, given the evidence available up to that point (weeks 1, 2, 3 and 4). Based on these distributions, for each dose the probability that it is the MED is evidenced by a probability exceeding the pre-specified threshold (Pu) of 0.9; the pre-specified threshold for an ineffective dose (Pl) was 0.1.
In this adaptive Bayesian trial, randomisation occurred in two stages. Stage 1 included 200mg CBD, 400mg CBD, 800mg CBD as well as placebo.
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End point type |
Primary
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End point timeframe |
During treatment weeks (1-4)
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Statistical analysis title |
Co-primary endpoint 2 (stage 1) | ||||||||||||||||||||
Statistical analysis description |
In this adaptive Bayesian trial, randomisation occurred in two stages. Stage 1 included 200mg CBD, 400mg CBD, 800mg CBD as well as placebo
Co-primary endpoint 2 (stage 1): more self-reported days abstinent compared to placebo: 200mg CBD P=0.0082; 400mg CBD P=0.9354; 800mg CBD P=0.8660
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Comparison groups |
Placebo v 200mg CBD v 400mg CBD v 800mg CBD
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Number of subjects included in analysis |
48
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | ||||||||||||||||||||
P-value |
> 0.9 [4] | ||||||||||||||||||||
Method |
Bayesian model | ||||||||||||||||||||
Confidence interval |
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Notes [3] - Aim: to identify the Most Effective Dose of CBD for reducing cannabis use compared to placebo (MED). A Bayesian model computed the predictive distribution of the outcome, given the evidence available up to that point (weeks 1, 2, 3 and 4). Based on these distributions, for each dose the probability that it is the MED is evidenced by a probability exceeding the pre-specified threshold (Pu) of 0.9; the pre-specified threshold for an ineffective dose (Pl) was 0.1. [4] - Co-primary endpoint 2 (stage 1): more self-reported days abstinent compared to placebo: 200mg CBD P=0.0082; 400mg CBD P=0.9354; 800mg CBD P=0.8660 |
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End point title |
Lower urinary THC-COOH:creatinine compared to placebo (stage 2) [5] | ||||||||||||||||
End point description |
Aim: to identify the Most Effective Dose of CBD for reducing cannabis use compared to placebo (MED). A Bayesian model computed the predictive distribution of the outcome, given the evidence available up to that point (weeks 1, 2, 3 and 4). Based on these distributions, for each dose the probability that it is the MED is evidenced by a probability exceeding the pre-specified threshold (Pu) of 0.9; the pre-specified threshold for an ineffective dose (Pl) was 0.1.
In this adaptive Bayesian trial, randomisation occurred in two stages. Stage 1 found evidence for ineffectiveness of 200mg CBD, therefore this dose was eliminated and no further randomisation occurred to this dose in stage 2. There was evidence for effectiveness of both 200mg CBD and 400mg CBD compared to placebo. Therefore in stage 2, randomisation continued to the existing groups of placebo, 400mg CBD and 800mg CBD.
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End point type |
Primary
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End point timeframe |
Treatment weeks (1-4)
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Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: All endpoints are reported with reference to placebo. |
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Statistical analysis title |
Co-primary endpoint 1 (stage 2) | ||||||||||||||||
Statistical analysis description |
Stage 1 found evidence for ineffectiveness of 200mg CBD, therefore this dose was eliminated and no further randomisation occurred to this dose in stage 2. There was evidence for effectiveness of both 200mg CBD and 400mg CBD compared to placebo. Therefore in stage 2, randomisation continued to the existing groups of placebo, 400mg CBD and 800mg CBD
Co-primary endpoint 1 (stage 2): lower urinary THC-COOH:creatinine compared to placebo: 400mg CBD P=0.9995; 800mg CBD P=0.9965
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Comparison groups |
400mg CBD v 800mg CBD v Placebo
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority [6] | ||||||||||||||||
P-value |
> 0.9 [7] | ||||||||||||||||
Method |
Bayesian model | ||||||||||||||||
Confidence interval |
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Notes [6] - Aim: to identify the Most Effective Dose of CBD for reducing cannabis use compared to placebo (MED). A Bayesian model computed the predictive distribution of the outcome, given the evidence available up to that point (weeks 1, 2, 3 and 4). Based on these distributions, for each dose the probability that it is the MED is evidenced by a probability exceeding the pre-specified threshold (Pu) of 0.9; the pre-specified threshold for an ineffective dose (Pl) was 0.1. [7] - Co-primary endpoint 1 (stage 2): lower urinary THC-COOH:creatinine compared to placebo: 400mg CBD P=0.9995; 800mg CBD P=0.9965 |
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End point title |
More self-reported days abstinent compared to placebo (stage 2) [8] | ||||||||||||||||
End point description |
Aim: to identify the Most Effective Dose of CBD for reducing cannabis use compared to placebo (MED). A Bayesian model computed the predictive distribution of the outcome, given the evidence available up to that point (weeks 1, 2, 3 and 4). Based on these distributions, for each dose the probability that it is the MED is evidenced by a probability exceeding the pre-specified threshold (Pu) of 0.9; the pre-specified threshold for an ineffective dose (Pl) was 0.1.
In this adaptive Bayesian trial, randomisation occurred in two stages. Stage 1 found evidence for ineffectiveness of 200mg CBD, therefore this dose was eliminated and no further randomisation occurred to this dose in stage 2. There was evidence for effectiveness of both 200mg CBD and 400mg CBD compared to placebo. Therefore in stage 2, randomisation continued to the existing groups of placebo, 400mg CBD and 800mg CBD.
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End point type |
Primary
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End point timeframe |
Treatment weeks (1-4)
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Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: All endpoints are reported with reference to placebo. |
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Statistical analysis title |
Co-primary endpoint 2 (stage 2) | ||||||||||||||||
Statistical analysis description |
Stage 1 found evidence for ineffectiveness of 200mg CBD, therefore this dose was eliminated and no further randomisation occurred to this dose in stage 2. There was evidence for effectiveness of both 200mg CBD and 400mg CBD compared to placebo. Therefore in stage 2, randomisation continued to the existing groups of placebo, 400mg CBD and 800mg CBD
Co-primary endpoint 2 (stage 2): more self-reported days abstinent compared to placebo: 400mg CBD P=0.9966; 800mg CBD P=0.9247
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Comparison groups |
Placebo v 400mg CBD v 800mg CBD
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority [9] | ||||||||||||||||
P-value |
> 0.9 [10] | ||||||||||||||||
Method |
Bayesian model | ||||||||||||||||
Confidence interval |
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Notes [9] - Aim: to identify the Most Effective Dose of CBD for reducing cannabis use compared to placebo (MED). A Bayesian model computed the predictive distribution of the outcome, given the evidence available up to that point (weeks 1, 2, 3 and 4). Based on these distributions, for each dose the probability that it is the MED is evidenced by a probability exceeding the pre-specified threshold (Pu) of 0.9; the pre-specified threshold for an ineffective dose (Pl) was 0.1. [10] - Co-primary endpoint 2 (stage 2): more self-reported days abstinent compared to placebo: 400mg CBD P=0.9966; 800mg CBD P=0.9247 |
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Adverse events information [1]
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Timeframe for reporting adverse events |
From randomisation to the final follow up (week 24)
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Adverse event reporting additional description |
Total number of adverse events (AEs) reported in each group
Placebo (n=23): mild (62), moderate (10), severe (0)
200mg CBD (n=12): mild (40), moderate (4), severe (0)
400mg CBD (n=24): mild (94), moderate (8), severe (0)
800mg CBD (n=23): mild (77), moderate (8), severe (0)
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
N/A | ||
Dictionary version |
0
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Frequency threshold for reporting non-serious adverse events: 5% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: For reasons of data compatibility the adverse events are reported in the text. Non serious adverse events are listed in this section. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
None reported |