A Pilot Study of GWP42003 in the Symptomatic Treatment of Ulcerative Colitis (GWID10160)

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01562314
• Collaborator: (none)
• Enrollment: 60
• Locations: 8
• Arms: 2
• Actual Duration (Months): 26.9
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study was conducted to determine the efficacy and safety 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 of treatment.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: GWP42003; Drug: Placebo	Phase 2

Detailed Description

This study was conducted by GW Research Ltd as a pilot study to determine the efficacy and safety of GWP42003 (50 milligram [mg] up to 250 mg twice daily [BID]), compared with placebo, as assessed by the percentage of participants achieving remission quantified as a Mayo score of 2 or less (with no sub-score >1) after 10 weeks of treatment. This was the first study to determine whether the study drug has a positive benefit for participants on their ulcerative colitis symptom control, as well as effects on inflammatory marker cytokines (C reactive protein [CRP]), a fecal inflammatory marker (calprotectin), stool frequency, and rectal bleeding. In addition, various inflammatory bowel disease (IBD) questionnaires were implemented in the study to observe further benefits on the study drug, compared with placebo.

This study was multi-center, randomized, double-blind, placebo-controlled, and parallel-group. The study consisted of a 7-day baseline period, a 10-week treatment period, and a 1-week follow-up period. Each participant had a Mayo assessment (including endoscopy) conducted to confirm eligibility. Eligible participants were randomized in a 1:1 ratio into the GWP42003 and placebo groups. At the start of the treatment period, participants entered a 2-week dose escalation period to achieve their maximum tolerated dose, up to 250 mg BID in the GWP42003 group. Participants remained at the maximum tolerated dose for the rest of the treatment period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Placebo-controlled Parallel Group, Pilot Study of GWP42003 in the Symptomatic Treatment of Ulcerative Colitis
• Actual Study Start Date: May 9, 2012
• Actual Primary Completion Date: Aug 5, 2014
• Actual Study Completion Date: Aug 5, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GWP42003 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.	Drug: GWP42003; 1 to 5 50 mg capsules taken BID; Other Names: Cannabidiol (CBD) Botanical Drug Substance (BDS)
Placebo Comparator: Placebo 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.	Drug: Placebo; 1 to 5 matching capsules taken BID; Other Names: Placebo control

Outcome Measures

Primary Outcome Measures

1. Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT [Baseline to End of Treatment (EOT) (10 weeks) or Early Termination (ET)]

   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); Physician's Global Assessment of Illness Severity (PGAS): 0 = none, 1 = mild, 2 = moderate, and 3 = severe.

2. Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT - PP Analysis [Baseline to EOT (10 weeks) or ET]

   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.

Secondary Outcome Measures

1. Distribution On The PGAS At EOT [EOT (10 weeks) or ET]

   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).

2. Distribution On The PGAS At EOT - PP Analysis [EOT (10 weeks) or ET]

   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).

3. Change From Baseline To EOT In The PGAS Score [Baseline to EOT (10 weeks) or ET]

   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.

4. Change From Baseline To EOT In The PGAS Score - PP Analysis [Baseline to EOT (10 weeks) or ET]

   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.

5. Change From Baseline To EOT In The Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score [Baseline to EOT (10 weeks) or ET]

   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.

6. Change From Baseline To EOT In The IBDQ Total Score - PP Analysis [Baseline to EOT (10 weeks) or ET]

   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.

7. Number Of Participants Who Reported An Improvement In The Subject Global Impression Of Change (SGIC) Questionnaire At EOT [Visit 4 (Day 43) to EOT (10 weeks) or ET]

   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.

8. Number Of Participants Who Reported An Improvement In The SGIC Questionnaire At EOT - PP Analysis [Visit 4 (Day 43) to EOT (10 weeks) or ET]

   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.

9. 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) [Baseline to EOT (last 7 days) or ET]

   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.

10. Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Stool Frequency NRS - PP Analysis [Baseline to EOT (last 7 days) or ET]

    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.

11. Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS [Baseline to EOT (last 7 days) or ET]

    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.

12. Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS - PP Analysis [Baseline to EOT (last 7 days) or ET]

    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.

13. Change From Baseline To EOT In The Mayo Total Score [Baseline to EOT (10 weeks) or ET]

    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.

14. Change From Baseline To EOT In The Mayo Partial Score [Baseline to EOT (10 weeks) or ET]

    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.

15. Change From Baseline To EOT In Levels Of Fecal Calprotectin [Baseline to EOT (10 weeks) or ET]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female participants aged 18 years or above;

• Participant diagnosed with mild to moderate ulcerative colitis and on a fixed dose of 5-Aminosalicylic (5-ASA) treatment and have been on a stable dose for at least 2 weeks prior to screening (0 mg dose of 5-ASA was acceptable);

• Participants at screening and baseline with a Mayo assessment score of greater than or equal to 4 (≥4) but less than or equal to 10 (≤10) and with an endoscopy score of at least 1 (≥1) , following an adequate exposure to oral and/ or topical 5-ASA, in the opinion of the investigator;

• In the opinion of the investigator, capable of complying with the study requirements and completing the study;

• Willing and able to give informed consent;

• Willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable;

• Willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study;

Exclusion Criteria:

• Severe ulcerative colitis (Mayo score of greater than 10 (>10);

• Ulcerative colitis only affecting the rectum (proctitis)

• Gastrointestinal infection evident from stool culture and testing for Clostridium difficile toxin (in the opinion of the investigator);

• Currently using or had used recreational cannabis, medicinal cannabis, cannabinoid medications (including Sativex®), or synthetic cannabinoid-based medications within 1 month prior to study entry and unwilling to abstain for the duration of the study;

• Any known or suspected history of alcohol or substance abuse, epilepsy or recurrent seizures, or hypersensitivity to cannabinoids;

• Was receiving a prohibited medication prior to screening and for the duration of the study;

• Previous non-responders to mono or polyclonal anti-Tumor Necrosis Factor antibodies;

• Personal or first degree relative, with history of schizophrenia or other psychosis;

• History of other significant psychiatric disorder or severe personality disorder (at the discretion of the investigator);

• Any known or suspected history of depression sufficient to require treatment with antidepressants or disrupt ordinary life (excluding episodes of reactive depression at the discretion of the investigator);

• Clinically significant cardiac, renal or hepatic impairment in the opinion of the investigator;

• Female participants who were pregnant, lactating or planning pregnancy during the course of the study and for 3 months from the date of last dose;

• Female participants of child bearing potential, unless willing to use 2 forms of contraception, 1 of which must have been a barrier contraception (for example, a female condom or occlusive cap [diaphragm or cervical vault/caps] with spermicide) during the study and for 3 months from the date of last dose (however a male condom should not have been used in conjunction with the female condom);

• Male participants whose partner was of child bearing potential, unless willing to use an appropriate barrier method of contraception (condom and spermicide) in addition to having their female partner use another form of barrier contraception (for example, an occlusive cap [diaphragm or cervical vault/caps] with spermicide) during the study and for 3 months from date of last dose (however a male condom should not have been used in conjunction with a female condom);

• Planned to travel outside the country of residence during the treatment phase of the study;

• Received an Investigational Medicinal Product (IMP) within 30 days prior to the screening visit;

• In the opinion of the investigator, was not considered to be suitable for the study;

• Any other significant disease or disorder which, in the opinion of the investigator, may either have put the participant at risk because of participation in the study, or may have influenced the result of the study or the participant's ability to participate in the study;

• Participant with any abnormalities that, in the opinion of the investigator, would prevent the participant from safe participation in the study;

• Unwilling to abstain from donation of blood during the study;

• Participants previously randomized into this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham		United Kingdom	B15 2TH
2		Coventry		United Kingdom	CV2 2DX
3		Liverpool		United Kingdom	L7 8XP
4		London		United Kingdom	NW1 2PG
5		London		United Kingdom	NW3 2QG
6		London		United Kingdom	SE1 7EH
7		Middlesex		United Kingdom	HA1 3UJ
8		Wigan		United Kingdom	WN1 2NN

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01562314
• Other Study ID Numbers: GWID10160; 2011-003208-19
• First Posted: Mar 23, 2012
• Last Update Posted: Aug 9, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Jazz Pharmaceuticals: Mild to Moderate Ulcerative Colitis; GWP42003
• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer; Cannabidiol

Study Results

Participant Flow

Arm/Group Title	GWP42003	Placebo
Arm/Group Description	GWP42003 was administered orally at a dose of 50 milligram (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.	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.
Period Title: Overall Study
STARTED	29	31
Received at Least 1 Dose of Study Drug	29	31
Intent-to-Treat (ITT) Analysis Set	29	31
Per Protocol (PP) Analysis Set	17	27
COMPLETED	16	23
NOT COMPLETED	13	8

Baseline Characteristics

Arm/Group Title	GWP42003	Placebo	Total
Arm/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.	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.	Total of all reporting groups
Overall Participants	29	31	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.78 (15.050)	42.82 (12.916)	43.77 (13.903)
Sex: Female, Male (Count of Participants)
Female	6 20.7%	10 32.3%	16 26.7%
Male	23 79.3%	21 67.7%	44 73.3%

Outcome Measures

1. Primary Outcome

Title	Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT
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); Physician's Global Assessment of Illness Severity (PGAS): 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
Time Frame	Baseline to End of Treatment (EOT) (10 weeks) or Early Termination (ET)

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	29	31
Count of Participants [Participants]	8 27.6%	8 25.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GWP42003, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7532
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.821
	Confidence Interval	(2-Sided) 90%; 0.292 to 2.309
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT - PP Analysis
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

PP analysis set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
Count of Participants [Participants]	7 24.1%	8 25.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GWP42003, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7032
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.300
	Confidence Interval	(2-Sided) 90%; 0.419 to 4.040
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Distribution On The PGAS At EOT
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).
Time Frame	EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	26	31
Normal	7 24.1%	5 16.1%
Mild Disease	13 44.8%	11 35.5%
Moderate Disease	6 20.7%	12 38.7%
Severe Disease	0 0%	3 9.7%

4. Secondary Outcome

Title	Distribution On The PGAS At EOT - PP Analysis
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).
Time Frame	EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

PP analysis set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
Normal	6 20.7%	5 16.1%
Mild Disease	8 27.6%	9 29%
Moderate Disease	3 10.3%	11 35.5%
Severe Disease	0 0%	2 6.5%

5. Secondary Outcome

Title	Change From Baseline To EOT In The PGAS Score
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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. Not all participants contributed data to this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	29	31
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)

6. Secondary Outcome

Title	Change From Baseline To EOT In The PGAS Score - PP Analysis
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

PP analysis set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
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)

7. Secondary Outcome

Title	Change From Baseline To EOT In The Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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. Not all participants contributed data for the outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	29	31
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)

8. Secondary Outcome

Title	Change From Baseline To EOT In The IBDQ Total Score - PP Analysis
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

PP analysis set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
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)

9. Secondary Outcome

Title	Number Of Participants Who Reported An Improvement In The Subject Global Impression Of Change (SGIC) Questionnaire At EOT
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.
Time Frame	Visit 4 (Day 43) to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	29	31
Visit 4 (Day 43)	15 51.7%	18 58.1%
Final Visit	23 79.3%	17 54.8%

10. Secondary Outcome

Title	Number Of Participants Who Reported An Improvement In The SGIC Questionnaire At EOT - PP Analysis
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.
Time Frame	Visit 4 (Day 43) to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

PP analysis set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
Visit 4 (Day 43)	14 48.3%	18 58.1%
Final Visit	16 55.2%	16 51.6%

11. Secondary Outcome

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)
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.
Time Frame	Baseline to EOT (last 7 days) or ET

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	29	31
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)

12. Secondary Outcome

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
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.
Time Frame	Baseline to EOT (last 7 days) or ET

Outcome Measure Data

Analysis Population Description

PP analysis set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
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)

13. Secondary Outcome

Title	Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS
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.
Time Frame	Baseline to EOT (last 7 days) or ET

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	29	31
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)

14. Secondary Outcome

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
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.
Time Frame	Baseline to EOT (last 7 days) or ET

Outcome Measure Data

Analysis Population Description

PP analysis set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
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)

15. Secondary Outcome

Title	Change From Baseline To EOT In The Mayo Total Score
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	29	31
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)

16. Secondary Outcome

Title	Change From Baseline To EOT In The Mayo Partial Score
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	29	31
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)

17. Secondary Outcome

Title	Change From Baseline To EOT In Levels Of Fecal Calprotectin
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

ITT analysis set: 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. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	29	31
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)

18. Post-Hoc Outcome

Title	Change From Baseline To EOT In The Mayo Total Score - PP Analysis
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

PP analysis set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
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)

19. Post-Hoc Outcome

Title	Change From Baseline To EOT In The Mayo Partial Score - PP Analysis Set
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

PP Analysis Set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
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)

20. Post-Hoc Outcome

Title	Change From Baseline To EOT In Levels Of Fecal Calprotectin- PP Analysis
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.
Time Frame	Baseline to EOT (10 weeks) or ET

Outcome Measure Data

Analysis Population Description

PP analysis set: all participants who completed the 10-week randomized phase of the study with no protocol violations deemed to compromise the assessments of efficacy. Not all participants contributed data for this outcome measure.

Arm/Group Title	GWP42003	Placebo
Arm/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.	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.
Measure Participants	17	27
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)

Adverse Events

Time Frame	Post-dose on Day 1 through 14 days after the final dose (up to 85 days).
Adverse Event Reporting Description	Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Arm/Group Title	GWP42003		Placebo
Arm/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.		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.
All Cause Mortality
	GWP42003		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	GWP42003		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		4/31 (12.9%)
Gastrointestinal disorders
Colitis ulcerative	0/29 (0%)		2/31 (6.5%)
General disorders
Chest pain	0/29 (0%)		1/31 (3.2%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/6 (0%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	GWP42003		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/29 (96.6%)		23/31 (74.2%)
Cardiac disorders
Palpitations	2/29 (6.9%)		0/31 (0%)
Gastrointestinal disorders
Abdominal discomfort	2/29 (6.9%)		1/31 (3.2%)
Abdominal distension	0/29 (0%)		3/31 (9.7%)
Abdominal pain	1/29 (3.4%)		5/31 (16.1%)
Colitis	1/29 (3.4%)		3/31 (9.7%)
Colitis ulcerative	1/29 (3.4%)		3/31 (9.7%)
Constipation	0/29 (0%)		3/31 (9.7%)
Dry mouth	4/29 (13.8%)		0/31 (0%)
Nausea	8/29 (27.6%)		3/31 (9.7%)
Vomiting	4/29 (13.8%)		0/31 (0%)
General disorders
Fatigue	4/29 (13.8%)		4/31 (12.9%)
Infections and infestations
Lower respiratory tract infection	3/29 (10.3%)		0/31 (0%)
Nasopharyngitis	2/29 (6.9%)		1/31 (3.2%)
Upper respiratory tract infection	2/29 (6.9%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/29 (0%)		3/31 (9.7%)
Muscle twitching	2/29 (6.9%)		0/31 (0%)
Nervous system disorders
Disturbance in attention	5/29 (17.2%)		0/31 (0%)
Dizziness	12/29 (41.4%)		3/31 (9.7%)
Headache	4/29 (13.8%)		4/31 (12.9%)
Lethargy	2/29 (6.9%)		2/31 (6.5%)
Memory impairment	3/29 (10.3%)		0/31 (0%)
Somnolence	10/29 (34.5%)		2/31 (6.5%)
Psychiatric disorders
Disorientation	4/29 (13.8%)		0/31 (0%)
Skin and subcutaneous tissue disorders
Rash	0/29 (0%)		3/31 (9.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.