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    Clinical Trial Results:
    A randomised, double-blind, placebo-controlled parallel group, pilot study of GWP42003 in the symptomatic treatment of ulcerative colitis.

    Summary
    EudraCT number
    2011-003208-19
    Trial protocol
    GB   CZ  
    Global end of trial date
    05 Aug 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    23 Sep 2018
    First version publication date
    23 Sep 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GWID10160
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01562314
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GW Research Ltd
    Sponsor organisation address
    Sovereign House, Vision Park, Chivers Way, Histon, Cambridge, United Kingdom, CB24 9BZ
    Public contact
    Alternate contact: medinfo@greenwichbiosciences.com, GW Research Ltd, medinfo@gwpharm.com
    Scientific contact
    Alternate contact: medinfo@greenwichbiosciences.com, GW Research Ltd, medinfo@gwpharm.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Mar 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Aug 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Aug 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the efficacy of GWP42003 compared with placebo by the percentage of participants achieving remission quantified as a MAYO score of 2 or less (with no sub-score >1) after 10 weeks treatment.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted. No study procedures were performed on study candidates until written consent had been obtained from the participant. The informed consent form, protocol, and amendments for this study were submitted to and approved by the institutional review board or independent ethics committee at each participating study.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    09 May 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 60
    Worldwide total number of subjects
    60
    EEA total number of subjects
    60
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    56
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Participants were screened for eligibility over a period of 7 days.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor
    Blinding implementation details
    To maintain blinding throughout, all capsule medication was formulated in such a way as to disguise the appearance, smell and taste of the active materials by the use of identical excipients and capsule shells. The maximum number of dose units administered was identical in both treatment groups.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    GWP42003
    Arm description
    GWP42003 was administered orally at a dose of 50 milligrams (mg) up to 250 mg, twice daily (BID), in the fasted state in the morning and evening, for 10 weeks. Following randomization, participants entered a 2-week dose escalation period to achieve their maximum tolerated dose, up to 500 mg, and maintained this dose for the rest of the treatment period. Participants were then followed for 1 week.
    Arm type
    Experimental

    Investigational medicinal product name
    GWP42003
    Investigational medicinal product code
    GWP42003
    Other name
    Cannabidiol (CBD), Botanical Drug Substance (BDS)
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 to 5 50 mg capsules taken BID

    Arm title
    Placebo
    Arm description
    Placebo capsules matching the study drug were administered orally, BID, in the fasted state in the morning and evening, for 10 weeks. Participants were then followed for 1 week.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Placebo control
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 to 5 matching capsules taken BID

    Number of subjects in period 1
    GWP42003 Placebo
    Started
    29
    31
    Received at least 1 dose of study drug
    29
    31
    Intent-to-Treat (ITT) Analysis Set
    29
    31
    Safety Analysis Set
    29
    31
    Per Protocol (PP) Analysis Set
    17
    27
    Completed
    16
    23
    Not completed
    13
    8
         Withdrawal by Subject
    -
    1
         Met Withdrawal Criteria
    3
    2
         Adverse Event
    10
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GWP42003
    Reporting group description
    GWP42003 was administered orally at a dose of 50 milligrams (mg) up to 250 mg, twice daily (BID), in the fasted state in the morning and evening, for 10 weeks. Following randomization, participants entered a 2-week dose escalation period to achieve their maximum tolerated dose, up to 500 mg, and maintained this dose for the rest of the treatment period. Participants were then followed for 1 week.

    Reporting group title
    Placebo
    Reporting group description
    Placebo capsules matching the study drug were administered orally, BID, in the fasted state in the morning and evening, for 10 weeks. Participants were then followed for 1 week.

    Reporting group values
    GWP42003 Placebo Total
    Number of subjects
    29 31 60
    Age categorical
    Units: Subjects
        18-64 years
    26 30 56
        65-84 years
    3 1 4
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    44.78 ± 15.050 42.82 ± 12.916 -
    Gender categorical
    Units: Subjects
        Female
    6 10 16
        Male
    23 21 44

    End points

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    End points reporting groups
    Reporting group title
    GWP42003
    Reporting group description
    GWP42003 was administered orally at a dose of 50 milligrams (mg) up to 250 mg, twice daily (BID), in the fasted state in the morning and evening, for 10 weeks. Following randomization, participants entered a 2-week dose escalation period to achieve their maximum tolerated dose, up to 500 mg, and maintained this dose for the rest of the treatment period. Participants were then followed for 1 week.

    Reporting group title
    Placebo
    Reporting group description
    Placebo capsules matching the study drug were administered orally, BID, in the fasted state in the morning and evening, for 10 weeks. Participants were then followed for 1 week.

    Subject analysis set title
    GWP42003 - ITT Analysis Set
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who were randomized and received at least 1 dose of study drug. Participants were analyzed according to the group to which they were randomized.

    Subject analysis set title
    Placebo - ITT Analysis Set
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who were randomized and received at least 1 dose of study drug. Participants were analyzed according to the group to which they were randomized.

    Subject analysis set title
    GWP42003 - PP Analysis Set
    Subject analysis set type
    Per protocol
    Subject analysis set description
    All participants without protocol violations that compromised the assessments of efficacy.

    Subject analysis set title
    Placebo - PP Analysis Set
    Subject analysis set type
    Per protocol
    Subject analysis set description
    All participants without protocol violations that compromised the assessments of efficacy.

    Primary: Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT

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    End point title
    Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT
    End point description
    The Mayo score is an assessment of ulcerative colitis activity. The Mayo total score ranges from 0 to 12 points with higher scores indicating more severe disease. The total score is made up of 4 sub-scores, each of which is assessed using a 0 to 3 scale. Sub-scores are graded as follows: Stool Frequency: 0 = Normal number of stools, 1 = 1 to 2 stools more than normal, 2 = 3 to 4 stools more than normal, 3 = 5 or more stools more than normal; Rectal Bleeding: 0 = No blood seen, 1 = Streaks of blood with stool less than half the time, 2 = Obvious blood with stool most of the time or more, 3 = Blood alone passes; Findings on Endoscopy: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration); PGAS: 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
    End point type
    Primary
    End point timeframe
    Baseline to End of Treatment (EOT) (10 weeks) or Early Termination (ET)
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    29
    31
    Units: count of participants
    8
    8
    Statistical analysis title
    Mayo Score Of 2 Or Less - ITT Analysis Set
    Comparison groups
    GWP42003 - ITT Analysis Set v Placebo - ITT Analysis Set
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7532
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.821
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.292
         upper limit
    2.309

    Primary: Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT - PP Analysis Set

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    End point title
    Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT - PP Analysis Set
    End point description
    The Mayo score is an assessment of ulcerative colitis activity. The Mayo total score ranges from 0 to 12 points with higher scores indicating more severe disease. The total score is made up of 4 sub-scores, each of which is assessed using a 0 to 3 scale. Sub-scores are graded as follows: Stool Frequency: 0 = Normal number of stools, 1 = 1 to 2 stools more than normal, 2 = 3 to 4 stools more than normal, 3 = 5 or more stools more than normal; Rectal Bleeding: 0 = No blood seen, 1 = Streaks of blood with stool less than half the time, 2 = Obvious blood with stool most of the time or more, 3 = Blood alone passes; Findings on Endoscopy: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration); PGAS: 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
    End point type
    Primary
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: count of participants
    7
    8
    Statistical analysis title
    Mayo Score Of 2 Or Less - PP Analysis Set
    Comparison groups
    Placebo - PP Analysis Set v GWP42003 - PP Analysis Set
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7032
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.3
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.419
         upper limit
    4.04

    Secondary: Distribution On The PGAS At EOT

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    End point title
    Distribution On The PGAS At EOT
    End point description
    The PGAS required the physician to assess participants’ disease severity on a 4-point scale (0 = normal [no disease], 1 = mild disease, 2 = moderate disease, 3 = severe disease).
    End point type
    Secondary
    End point timeframe
    EOT (10 weeks) or ET
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    26
    31
    Units: count of participants
        Normal
    7
    5
        Mild Disease
    13
    11
        Moderate Disease
    6
    12
        Severe Disease
    0
    3
    No statistical analyses for this end point

    Secondary: Distribution On The PGAS At EOT - PP Analysis

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    End point title
    Distribution On The PGAS At EOT - PP Analysis
    End point description
    The PGAS required the physician to assess participants’ disease severity on a 4-point scale (0 = normal [no disease], 1 = mild disease, 2 = moderate disease, 3 = severe disease).
    End point type
    Secondary
    End point timeframe
    EOT (10 weeks) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: count of participants
        Normal
    6
    5
        Mild Disease
    8
    9
        Moderate Disease
    3
    11
        Severe Disease
    0
    2
    No statistical analyses for this end point

    Secondary: Change From Baseline To EOT In The PGAS Score

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    End point title
    Change From Baseline To EOT In The PGAS Score
    End point description
    The PGAS required the physician to assess participants’ disease severity on a 4-point scale (0 = normal [no disease], 1 = mild disease, 2 = moderate disease, 3 = severe disease). A negative change from Baseline indicates that symptoms decreased.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    29
    31
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    1.7 ± 0.45
    1.8 ± 0.48
        Final Visit
    1.0 ± 0.72
    1.4 ± 0.89
        Change From Baseline
    -0.8 ± 0.82
    -0.4 ± 0.95
    No statistical analyses for this end point

    Secondary: Change From Baseline To EOT In The PGAS Score - PP Analysis

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    End point title
    Change From Baseline To EOT In The PGAS Score - PP Analysis
    End point description
    The PGAS required the physician to assess participants’ disease severity on a 4-point scale (0 = normal [no disease], 1 = mild disease, 2 = moderate disease, 3 = severe disease). A negative change from Baseline indicates that symptoms decreased.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    1.8 ± 0.44
    1.8 ± 0.51
        Final Visit
    0.8 ± 0.73
    1.4 ± 0.88
        Change From Baseline
    -0.9 ± 0.83
    -0.4 ± 0.97
    No statistical analyses for this end point

    Secondary: Change From Baseline To EOT In The Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score

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    End point title
    Change From Baseline To EOT In The Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score
    End point description
    The IBDQ is a validated and reliable tool to measure health-related quality of life in adult participants with inflammatory bowel disease (IBD). Each of the 32 questions falls into 1 of 4 domains (bowel symptoms, systemic symptoms, emotional status, and social function). The 32 questions each have 7 possible responses. Each response is assigned a score ranging from 1 to 7, indicating the severity (1 being least favorable and 7 being the most favorable). Individual question scores were summed to give the IBDQ total score (range: 32 to 224 points). A positive change from Baseline indicates that symptoms improved.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    29
    31
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    138.5 ± 32.37
    129.1 ± 38.02
        Final Visit
    164.2 ± 29.13
    146.8 ± 47.50
        Change From Baseline
    24.6 ± 35.51
    16.7 ± 36.33
    No statistical analyses for this end point

    Secondary: Change From Baseline To EOT In The IBDQ Total Score - PP Analysis

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    End point title
    Change From Baseline To EOT In The IBDQ Total Score - PP Analysis
    End point description
    The IBDQ is a validated and reliable tool to measure health-related quality of life in adult participants with IBD. Each of the 32 questions falls into 1 of 4 domains (bowel symptoms, systemic symptoms, emotional status, and social function). The 32 questions each have 7 possible responses. Each response is assigned a score ranging from 1 to 7, indicating the severity (1 being least favorable and 7 being the most favorable). Individual question scores were summed to give the IBDQ total score (range: 32 to 224 points). A positive change from Baseline indicates that symptoms improved.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    134.0 ± 35.58
    134.0 ± 37.30
        Final Visit
    172.8 ± 28.52
    150.5 ± 48.87
        Change From Baseline
    39.3 ± 39.81
    15.4 ± 33.65
    No statistical analyses for this end point

    Secondary: Number Of Participants Who Reported An Improvement In The Subject Global Impression Of Change (SGIC) Questionnaire At EOT

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    End point title
    Number Of Participants Who Reported An Improvement In The Subject Global Impression Of Change (SGIC) Questionnaire At EOT
    End point description
    Participants were asked to answer the following question by using a 7-point scale (1 = very much better to 7 = very much worse): “Please assess the change in your ulcerative colitis symptoms since immediately before receiving the first dose of study treatment.” Improvement was considered as very much better, much better, or minimally better.
    End point type
    Secondary
    End point timeframe
    Visit 4 (Day 43) to EOT (10 weeks) or ET
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    29
    31
    Units: count of participants
        Visit 4 (Day 43)
    15
    18
        Final Visit
    23
    17
    No statistical analyses for this end point

    Secondary: Number Of Participants Who Reported An Improvement In The SGIC Questionnaire At EOT - PP Analysis

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    End point title
    Number Of Participants Who Reported An Improvement In The SGIC Questionnaire At EOT - PP Analysis
    End point description
    Participants were asked to answer the following question by using a 7-point scale (1 = very much better to 7 = very much worse): “Please assess the change in your ulcerative colitis symptoms since immediately before receiving the first dose of study treatment.” Improvement was considered as very much better, much better, or minimally better.
    End point type
    Secondary
    End point timeframe
    Visit 4 (Day 43) to EOT (10 weeks) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: count of participants
        Visit 4 (Day 43)
    14
    18
        Final Visit
    16
    16
    No statistical analyses for this end point

    Secondary: Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Stool Frequency Numerical Rating Scale (NRS)

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    End point title
    Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Stool Frequency Numerical Rating Scale (NRS)
    End point description
    Participants were required to record their stool frequency during the baseline and treatment periods in a daily diary. Participants graded stool frequency with a 4-point NRS as follows: 0 = Normal number of stools; 1 = 1 to 2 stools more than normal; 2 = 3 to 4 stools more than normal; 3 = 5 or more stools more than normal. For analysis, the baseline value was defined as the mean stool frequency score of the last 7 available days of the baseline period; the EOT value was defined as the mean stool frequency score of last 7 days of the treatment period, or last 7 days for which study drug was taken, where earlier. A negative change from Baseline indicates that symptoms improved.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (last 7 days) or ET
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    29
    31
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    1.50 ± 0.937
    1.89 ± 0.814
        Last 7 Days
    1.05 ± 0.930
    1.46 ± 0.888
        Change From Baseline
    -0.43 ± 0.563
    -0.43 ± 0.816
    No statistical analyses for this end point

    Secondary: Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Stool Frequency NRS - PP Analysis

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    End point title
    Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Stool Frequency NRS - PP Analysis
    End point description
    Participants were required to record their stool frequency during the baseline and treatment periods in a daily diary. Participants graded stool frequency with a 4-point NRS as follows: 0 = Normal number of stools; 1 = 1 to 2 stools more than normal; 2 = 3 to 4 stools more than normal; 3 = 5 or more stools more than normal. For analysis, the baseline value was defined as the mean stool frequency score of the last 7 available days of the baseline period; the EOT value was defined as the mean stool frequency score of last 7 days of the treatment period, or last 7 days for which study drug was taken, where earlier. A negative change from Baseline indicates that symptoms improved.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (last 7 days) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    1.37 ± 0.875
    1.81 ± 0.827
        Last 7 Days
    0.73 ± 0.689
    1.36 ± 0.871
        Change From Baseline
    -0.64 ± 0.497
    -0.45 ± 0.768
    No statistical analyses for this end point

    Secondary: Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS

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    End point title
    Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS
    End point description
    Participants were required to record their rectal bleeding during the baseline and treatment periods in a daily diary. Participants graded rectal bleeding with a 4-point NRS as follows: 0 = No blood seen, 1 = Streaks of blood with stool less than half the time, 2 = Obvious blood with stool most of the time or more, 3 = Blood alone passes. For analysis, the baseline value was defined as the mean rectal bleeding score of the last 7 available days of the baseline period; the EOT value was defined as the mean rectal bleeding score of last 7 days of the treatment period, or last 7 days for which study drug was taken, where earlier. A negative change from Baseline indicates that symptoms improved.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (last 7 days) or ET
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    29
    31
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    0.96 ± 0.829
    1.19 ± 0.816
        Last 7 Days
    0.48 ± 0.711
    0.84 ± 0.863
        Change From Baseline
    -0.44 ± 0.709
    -0.35 ± 0.794
    No statistical analyses for this end point

    Secondary: Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS - PP Analysis

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    End point title
    Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS - PP Analysis
    End point description
    Participants were required to record their rectal bleeding during the baseline and treatment periods in a daily diary. Participants graded rectal bleeding with a 4-point NRS as follows: 0 = No blood seen, 1 = Streaks of blood with stool less than half the time, 2 = Obvious blood with stool most of the time or more, 3 = Blood alone passes. For analysis, the baseline value was defined as the mean rectal bleeding score of the last 7 available days of the baseline period; the EOT value was defined as the mean rectal bleeding score of last 7 days of the treatment period, or last 7 days for which study drug was taken, where earlier. A negative change from Baseline indicates that symptoms improved.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (last 7 days) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    0.82 ± 0.682
    1.16 ± 0.831
        Last 7 Days
    0.24 ± 0.367
    0.80 ± 0.875
        Change From Baseline
    -0.58 ± 0.793
    -0.35 ± 0.773
    No statistical analyses for this end point

    Secondary: Change From Baseline To EOT In The Mayo Total Score

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    End point title
    Change From Baseline To EOT In The Mayo Total Score
    End point description
    The Mayo score is an assessment of ulcerative colitis activity. The Mayo total score ranges from 0 to 12 points with higher scores indicating more severe disease. The total score is made up of 4 sub-scores (assessed using a 0 to 3 scale). The sub-scores are graded as follows: Stool Frequency: 0 = Normal number of stools, 1 = 1 to 2 stools more than normal, 2 = 3 to 4 stools more than normal, 3 = 5 or more stools more than normal; Rectal Bleeding: 0 = No blood seen, 1 = Streaks of blood with stool less than half the time, 2 = Obvious blood with stool most of the time or more, 3 = Blood alone passes; Findings on Endoscopy: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration); PGAS: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. A negative change from Baseline indicates that symptoms improved.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    29
    31
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    6.3 ± 1.73
    7.0 ± 2.01
        Final Visit
    3.0 ± 2.25
    4.9 ± 3.22
        Change From Baseline
    -3.0 ± 2.40
    -1.8 ± 2.73
    No statistical analyses for this end point

    Secondary: Change From Baseline To EOT In The Mayo Partial Score

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    End point title
    Change From Baseline To EOT In The Mayo Partial Score
    End point description
    The Mayo score is an assessment of ulcerative colitis activity. The Mayo partial score does not include the endoscopy findings sub-score and ranges from 0 to 9 points with higher scores indicating more severe disease. The partial score is made up of 3 sub-scores (assessed by using a 0 to 3 scale). The sub-scores are graded as follows: Stool Frequency: 0 = Normal number of stools, 1 = 1 to 2 stools more than normal, 2 = 3 to 4 stools more than normal, 3 = 5 or more stools more than normal; Rectal Bleeding: 0 = No blood seen, 1 = Streaks of blood with stool less than half the time, 2 = Obvious blood with stool most of the time or more, 3 = Blood alone passes; PGAS: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. A negative change from Baseline indicates that symptoms improved.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    29
    31
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    4.4 ± 1.57
    5.1 ± 1.61
        Final Visit
    2.3 ± 1.73
    3.8 ± 2.60
        Change From Baseline
    -2.0 ± 2.00
    -1.2 ± 2.14
    No statistical analyses for this end point

    Secondary: Change From Baseline To EOT In Levels Of Fecal Calprotectin

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    End point title
    Change From Baseline To EOT In Levels Of Fecal Calprotectin
    End point description
    Fecal calprotectin is a marker of inflammation. Standard methods were used to measure the levels of calprotectin in fecal samples collected at the end of baseline and treatment periods. A negative change from Baseline indicates that levels of fecal calprotectin decreased.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - ITT Analysis Set Placebo - ITT Analysis Set
    Number of subjects analysed
    29
    31
    Units: microgram calprotectin/gram feces (ug/g)
    arithmetic mean (standard deviation)
        Baseline
    490.6 ± 197.41
    462.3 ± 227.35
        Final Visit
    397.3 ± 241.08
    428.0 ± 229.38
        Change From Baseline
    -91.6 ± 295.77
    -51.3 ± 289.32
    No statistical analyses for this end point

    Post-hoc: Change From Baseline To EOT In The Mayo Total Score - PP Analysis

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    End point title
    Change From Baseline To EOT In The Mayo Total Score - PP Analysis
    End point description
    The Mayo score is an assessment of ulcerative colitis activity. The Mayo total score ranges from 0 to 12 points with higher scores indicating more severe disease. The total score is made up of 4 sub-scores (assessed using a 0 to 3 scale). The sub-scores are graded as follows: Stool Frequency: 0 = Normal number of stools, 1 = 1 to 2 stools more than normal, 2 = 3 to 4 stools more than normal, 3 = 5 or more stools more than normal; Rectal Bleeding: 0 = No blood seen, 1 = Streaks of blood with stool less than half the time, 2 = Obvious blood with stool most of the time or more, 3 = Blood alone passes; Findings on Endoscopy: 0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration); PGAS: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. A negative change from Baseline indicates that symptoms improved.
    End point type
    Post-hoc
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    6.0 ± 1.70
    6.8 ± 2.04
        Final Visit
    2.8 ± 2.02
    4.7 ± 3.24
        Change From Baseline
    -3.2 ± 2.25
    -1.9 ± 2.81
    No statistical analyses for this end point

    Post-hoc: Change From Baseline To EOT In The Mayo Partial Score - PP Analysis Set

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    End point title
    Change From Baseline To EOT In The Mayo Partial Score - PP Analysis Set
    End point description
    The Mayo score is an assessment of ulcerative colitis activity. The Mayo partial score does not include the endoscopy findings sub-score and ranges from 0 to 9 points with higher scores indicating more severe disease. The partial score is made up of 3 sub-scores (assessed by using a 0 to 3 scale). The sub-scores are graded as follows: Stool Frequency: 0 = Normal number of stools, 1 = 1 to 2 stools more than normal, 2 = 3 to 4 stools more than normal, 3 = 5 or more stools more than normal; Rectal Bleeding: 0 = No blood seen, 1 = Streaks of blood with stool less than half the time, 2 = Obvious blood with stool most of the time or more, 3 = Blood alone passes; PGAS: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. A negative change from Baseline indicates that symptoms improved.
    End point type
    Post-hoc
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    4.1 ± 1.50
    4.9 ± 1.63
        Final Visit
    1.7 ± 1.53
    3.7 ± 2.66
        Change From Baseline
    -2.4 ± 2.03
    -1.2 ± 2.17
    No statistical analyses for this end point

    Post-hoc: Change From Baseline To EOT In Levels Of Fecal Calprotectin- PP Analysis

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    End point title
    Change From Baseline To EOT In Levels Of Fecal Calprotectin- PP Analysis
    End point description
    Fecal calprotectin is a marker of inflammation. Standard methods were used to measure the levels of calprotectin in fecal samples collected at the end of baseline and treatment periods. A negative change from Baseline indicates that levels of fecal calprotectin decreased.
    End point type
    Post-hoc
    End point timeframe
    Baseline to EOT (10 weeks) or ET
    End point values
    GWP42003 - PP Analysis Set Placebo - PP Analysis Set
    Number of subjects analysed
    17
    27
    Units: ug/g
    arithmetic mean (standard deviation)
        Baseline
    527.9 ± 164.14
    440.3 ± 237.99
        Final Visit
    355.9 ± 247.75
    408.9 ± 238.94
        Change From Baseline
    -155.9 ± 306.84
    -51.9 ± 311.56
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Post-dose on Day 1 through 14 days after the final dose (up to 85 days).
    Adverse event reporting additional description
    Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    GWP42003
    Reporting group description
    GWP42003 was administered orally at a dose of 50 mg up to 250 mg, BID, in the fasted state in the morning and evening, for 10 weeks. Following randomization, participants entered a 2-week dose escalation period to achieve their maximum tolerated dose, up to 500 mg, and maintained this dose for the rest of the treatment period. Participants were then followed for 1 week.

    Reporting group title
    Placebo
    Reporting group description
    Placebo capsules matching the study drug were administered orally, BID, in the fasted state in the morning and evening, for 10 weeks. Participants were then followed for 1 week.

    Serious adverse events
    GWP42003 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 29 (0.00%)
    4 / 31 (12.90%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed [1]
    0 / 6 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis ulcerative
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 31 (6.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This SAE affects only female participants.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    GWP42003 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    28 / 29 (96.55%)
    23 / 31 (74.19%)
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 31 (0.00%)
         occurrences all number
    2
    0
    Nervous system disorders
    Disturbance in attention
         subjects affected / exposed
    5 / 29 (17.24%)
    0 / 31 (0.00%)
         occurrences all number
    5
    0
    Dizziness
         subjects affected / exposed
    12 / 29 (41.38%)
    3 / 31 (9.68%)
         occurrences all number
    13
    3
    Headache
         subjects affected / exposed
    4 / 29 (13.79%)
    4 / 31 (12.90%)
         occurrences all number
    4
    4
    Lethargy
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 31 (6.45%)
         occurrences all number
    2
    2
    Memory impairment
         subjects affected / exposed
    3 / 29 (10.34%)
    0 / 31 (0.00%)
         occurrences all number
    3
    0
    Somnolence
         subjects affected / exposed
    10 / 29 (34.48%)
    2 / 31 (6.45%)
         occurrences all number
    11
    2
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 29 (13.79%)
    4 / 31 (12.90%)
         occurrences all number
    5
    4
    Psychiatric disorders
    Disorientation
         subjects affected / exposed
    4 / 29 (13.79%)
    0 / 31 (0.00%)
         occurrences all number
    4
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 31 (3.23%)
         occurrences all number
    2
    1
    Abdominal distension
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 31 (9.68%)
         occurrences all number
    0
    3
    Abdominal pain
         subjects affected / exposed
    1 / 29 (3.45%)
    5 / 31 (16.13%)
         occurrences all number
    1
    5
    Colitis
         subjects affected / exposed
    1 / 29 (3.45%)
    3 / 31 (9.68%)
         occurrences all number
    1
    3
    Colitis ulcerative
         subjects affected / exposed
    1 / 29 (3.45%)
    3 / 31 (9.68%)
         occurrences all number
    1
    3
    Constipation
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 31 (9.68%)
         occurrences all number
    0
    3
    Dry mouth
         subjects affected / exposed
    4 / 29 (13.79%)
    0 / 31 (0.00%)
         occurrences all number
    5
    0
    Nausea
         subjects affected / exposed
    8 / 29 (27.59%)
    3 / 31 (9.68%)
         occurrences all number
    8
    3
    Vomiting
         subjects affected / exposed
    4 / 29 (13.79%)
    0 / 31 (0.00%)
         occurrences all number
    4
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 31 (9.68%)
         occurrences all number
    0
    3
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 31 (9.68%)
         occurrences all number
    0
    3
    Muscle twitching
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 31 (0.00%)
         occurrences all number
    2
    0
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 29 (10.34%)
    0 / 31 (0.00%)
         occurrences all number
    3
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 31 (3.23%)
         occurrences all number
    2
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 31 (0.00%)
         occurrences all number
    2
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Nov 2011
    The amendment to this study updated contact details following GW Pharmaceuticals Ltd. office relocation.
    24 Jun 2013
    The amendment to this study amended the protocol to remove the lower dose limit of study drug. Topical treatments for ulcerative colitis within 2 weeks prior to screening were originally prohibited in the study protocol. This was changed so that participants on a stable dose of topical therapy for ulcerative colitis could be eligible in some circumstances. The amendment also divided the exclusion criterion 6.2.8 into 2 so that investigators could act at their discretion as to whether a participant with a history of significant psychiatric disorder or severe personality disorder was eligible for the study. Finally, the amendment resolved minor errors, inconsistencies and clarity issues.
    21 Aug 2013
    The amendment to this study further amendment the Prohibited Therapy section of the protocol to disallow topical treatments for ulcerative colitis within the last 2 weeks prior to the screening endoscopy. The amendment also included 3 minor administrative corrections.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/29538683
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