Trial Outcomes & Findings for A Pilot Study of GWP42003 in the Symptomatic Treatment of Ulcerative Colitis (GWID10160) (NCT NCT01562314)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Baseline to End of Treatment (EOT) (10 weeks) or Early Termination (ET)

Results posted on

2018-08-09

Participant Flow

Participant milestones

Participant milestones
Measure	GWP42003 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 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.
Overall Study STARTED	29	31
Overall Study Received at Least 1 Dose of Study Drug	29	31
Overall Study Intent-to-Treat (ITT) Analysis Set	29	31
Overall Study Per Protocol (PP) Analysis Set	17	27
Overall Study COMPLETED	16	23
Overall Study NOT COMPLETED	13	8

Reasons for withdrawal

Reasons for withdrawal
Measure	GWP42003 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 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.
Overall Study Adverse Event	10	5
Overall Study Met Withdrawal Criteria	3	2
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GWP42003 n=29 Participants 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 n=31 Participants 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 n=60 Participants Total of all reporting groups
Age, Continuous	44.78 years STANDARD_DEVIATION 15.050 • n=5 Participants	42.82 years STANDARD_DEVIATION 12.916 • n=7 Participants	43.77 years STANDARD_DEVIATION 13.903 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	21 Participants n=7 Participants	44 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to End of Treatment (EOT) (10 weeks) or Early Termination (ET)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=29 Participants 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.
Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT	8 Participants	8 Participants

PRIMARY outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT - PP Analysis	8 Participants	7 Participants

SECONDARY outcome

Timeframe: EOT (10 weeks) or ET

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=26 Participants 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.
Distribution On The PGAS At EOT Normal	5 Participants	7 Participants
Distribution On The PGAS At EOT Mild Disease	11 Participants	13 Participants
Distribution On The PGAS At EOT Moderate Disease	12 Participants	6 Participants
Distribution On The PGAS At EOT Severe Disease	3 Participants	0 Participants

SECONDARY outcome

Timeframe: EOT (10 weeks) or ET

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
Distribution On The PGAS At EOT - PP Analysis Normal	5 Participants	6 Participants
Distribution On The PGAS At EOT - PP Analysis Mild Disease	9 Participants	8 Participants
Distribution On The PGAS At EOT - PP Analysis Moderate Disease	11 Participants	3 Participants
Distribution On The PGAS At EOT - PP Analysis Severe Disease	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=29 Participants 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.
Change From Baseline To EOT In The PGAS Score Baseline	1.8 units on a scale Standard Deviation 0.48	1.7 units on a scale Standard Deviation 0.45
Change From Baseline To EOT In The PGAS Score Final Visit	1.4 units on a scale Standard Deviation 0.89	1.0 units on a scale Standard Deviation 0.72
Change From Baseline To EOT In The PGAS Score Change From Baseline	-0.4 units on a scale Standard Deviation 0.95	-0.8 units on a scale Standard Deviation 0.82

SECONDARY outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
Change From Baseline To EOT In The PGAS Score - PP Analysis Baseline	1.8 units on a scale Standard Deviation 0.51	1.8 units on a scale Standard Deviation 0.44
Change From Baseline To EOT In The PGAS Score - PP Analysis Final Visit	1.4 units on a scale Standard Deviation 0.88	0.8 units on a scale Standard Deviation 0.73
Change From Baseline To EOT In The PGAS Score - PP Analysis Change From Baseline	-0.4 units on a scale Standard Deviation 0.97	-0.9 units on a scale Standard Deviation 0.83

SECONDARY outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=29 Participants 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.
Change From Baseline To EOT In The Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score Baseline	129.1 units on a scale Standard Error 38.02	138.5 units on a scale Standard Error 32.37
Change From Baseline To EOT In The Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score Final Visit	146.8 units on a scale Standard Error 47.50	164.2 units on a scale Standard Error 29.13
Change From Baseline To EOT In The Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score Change From Baseline	16.7 units on a scale Standard Error 36.33	24.6 units on a scale Standard Error 35.51

SECONDARY outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
Change From Baseline To EOT In The IBDQ Total Score - PP Analysis Baseline	134.0 units on a scale Standard Deviation 37.30	134.0 units on a scale Standard Deviation 35.58
Change From Baseline To EOT In The IBDQ Total Score - PP Analysis Final Visit	150.5 units on a scale Standard Deviation 48.87	172.8 units on a scale Standard Deviation 28.52
Change From Baseline To EOT In The IBDQ Total Score - PP Analysis Change From Baseline	15.4 units on a scale Standard Deviation 33.65	39.3 units on a scale Standard Deviation 39.81

SECONDARY outcome

Timeframe: Visit 4 (Day 43) to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=29 Participants 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.
Number Of Participants Who Reported An Improvement In The Subject Global Impression Of Change (SGIC) Questionnaire At EOT Visit 4 (Day 43)	18 Participants	15 Participants
Number Of Participants Who Reported An Improvement In The Subject Global Impression Of Change (SGIC) Questionnaire At EOT Final Visit	17 Participants	23 Participants

SECONDARY outcome

Timeframe: Visit 4 (Day 43) to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
Number Of Participants Who Reported An Improvement In The SGIC Questionnaire At EOT - PP Analysis Visit 4 (Day 43)	18 Participants	14 Participants
Number Of Participants Who Reported An Improvement In The SGIC Questionnaire At EOT - PP Analysis Final Visit	16 Participants	16 Participants

SECONDARY outcome

Timeframe: Baseline to EOT (last 7 days) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=29 Participants 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.
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) Last 7 Days	1.46 units on a scale Standard Deviation 0.888	1.05 units on a scale Standard Deviation 0.930
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	1.89 units on a scale Standard Deviation 0.814	1.50 units on a scale Standard Deviation 0.937
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) Change From Baseline	-0.43 units on a scale Standard Deviation 0.816	-0.43 units on a scale Standard Deviation 0.563

SECONDARY outcome

Timeframe: Baseline to EOT (last 7 days) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
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	1.81 units on a scale Standard Deviation 0.827	1.37 units on a scale Standard Deviation 0.875
Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Stool Frequency NRS - PP Analysis Last 7 Days	1.36 units on a scale Standard Deviation 0.871	0.73 units on a scale Standard Deviation 0.689
Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Stool Frequency NRS - PP Analysis Change From Baseline	-0.45 units on a scale Standard Deviation 0.768	-0.64 units on a scale Standard Deviation 0.497

SECONDARY outcome

Timeframe: Baseline to EOT (last 7 days) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=29 Participants 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.
Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS Baseline	1.19 units on a scale Standard Deviation 0.816	0.96 units on a scale Standard Deviation 0.829
Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS Last 7 Days	0.84 units on a scale Standard Deviation 0.863	0.48 units on a scale Standard Deviation 0.711
Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS Change From Baseline	-0.35 units on a scale Standard Deviation 0.794	-0.44 units on a scale Standard Deviation 0.709

SECONDARY outcome

Timeframe: Baseline to EOT (last 7 days) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
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	1.16 units on a scale Standard Deviation 0.831	0.82 units on a scale Standard Deviation 0.682
Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS - PP Analysis Last 7 Days	0.80 units on a scale Standard Deviation 0.875	0.24 units on a scale Standard Deviation 0.367
Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS - PP Analysis Change From Baseline	-0.35 units on a scale Standard Deviation 0.773	-0.58 units on a scale Standard Deviation 0.793

SECONDARY outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=29 Participants 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.
Change From Baseline To EOT In The Mayo Total Score Baseline	7.0 units on a scale Standard Deviation 2.01	6.3 units on a scale Standard Deviation 1.73
Change From Baseline To EOT In The Mayo Total Score Final Visit	4.9 units on a scale Standard Deviation 3.22	3.0 units on a scale Standard Deviation 2.25
Change From Baseline To EOT In The Mayo Total Score Change From Baseline	-1.8 units on a scale Standard Deviation 2.73	-3.0 units on a scale Standard Deviation 2.40

SECONDARY outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=29 Participants 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.
Change From Baseline To EOT In The Mayo Partial Score Baseline	5.1 units on a scale Standard Deviation 1.61	4.4 units on a scale Standard Deviation 1.57
Change From Baseline To EOT In The Mayo Partial Score Final Visit	3.8 units on a scale Standard Deviation 2.60	2.3 units on a scale Standard Deviation 1.73
Change From Baseline To EOT In The Mayo Partial Score Change From Baseline	-1.2 units on a scale Standard Deviation 2.14	-2.0 units on a scale Standard Deviation 2.00

SECONDARY outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	GWP42003 n=29 Participants 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.
Change From Baseline To EOT In Levels Of Fecal Calprotectin Baseline	462.3 microgram calprotectin/gram feces (ug/g) Standard Deviation 227.35	490.6 microgram calprotectin/gram feces (ug/g) Standard Deviation 197.41
Change From Baseline To EOT In Levels Of Fecal Calprotectin Final Visit	428.0 microgram calprotectin/gram feces (ug/g) Standard Deviation 229.38	397.3 microgram calprotectin/gram feces (ug/g) Standard Deviation 241.08
Change From Baseline To EOT In Levels Of Fecal Calprotectin Change from Baseline	-51.3 microgram calprotectin/gram feces (ug/g) Standard Deviation 289.32	-91.6 microgram calprotectin/gram feces (ug/g) Standard Deviation 295.77

POST_HOC outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
Change From Baseline To EOT In The Mayo Total Score - PP Analysis Baseline	6.8 units on a scale Standard Deviation 2.04	6.0 units on a scale Standard Deviation 1.70
Change From Baseline To EOT In The Mayo Total Score - PP Analysis Final Visit	4.7 units on a scale Standard Deviation 3.24	2.8 units on a scale Standard Deviation 2.02
Change From Baseline To EOT In The Mayo Total Score - PP Analysis Change From Baseline	-1.9 units on a scale Standard Deviation 2.81	-3.2 units on a scale Standard Deviation 2.25

POST_HOC outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
Change From Baseline To EOT In The Mayo Partial Score - PP Analysis Set Baseline	4.9 units on a scale Standard Deviation 1.63	4.1 units on a scale Standard Deviation 1.50
Change From Baseline To EOT In The Mayo Partial Score - PP Analysis Set Final Visit	3.7 units on a scale Standard Deviation 2.66	1.7 units on a scale Standard Deviation 1.53
Change From Baseline To EOT In The Mayo Partial Score - PP Analysis Set Change From Baseline	-1.2 units on a scale Standard Deviation 2.17	-2.4 units on a scale Standard Deviation 2.03

POST_HOC outcome

Timeframe: Baseline to EOT (10 weeks) or ET

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants 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.	GWP42003 n=17 Participants 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.
Change From Baseline To EOT In Levels Of Fecal Calprotectin- PP Analysis Baseline	440.3 ug/g Standard Deviation 237.99	527.9 ug/g Standard Deviation 164.14
Change From Baseline To EOT In Levels Of Fecal Calprotectin- PP Analysis Final Visit	408.9 ug/g Standard Deviation 238.94	355.9 ug/g Standard Deviation 247.75
Change From Baseline To EOT In Levels Of Fecal Calprotectin- PP Analysis Change From Baseline	-51.9 ug/g Standard Deviation 311.56	-155.9 ug/g Standard Deviation 306.84

Adverse Events

GWP42003

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GWP42003 n=29 participants at risk 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 n=31 participants at risk 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.
Gastrointestinal disorders Colitis ulcerative	0.00% 0/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	6.5% 2/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
General disorders Chest pain	0.00% 0/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	3.2% 1/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.00% 0/6 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	10.0% 1/10 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.

Other adverse events

Additional Information

Medical Enquiries

GW Research Ltd

Email: [email protected], [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	GWP42003 n=29 participants at risk 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 n=31 participants at risk 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.
Cardiac disorders Palpitations	6.9% 2/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	0.00% 0/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Gastrointestinal disorders Abdominal discomfort	6.9% 2/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	3.2% 1/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Gastrointestinal disorders Abdominal distension	0.00% 0/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	9.7% 3/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Gastrointestinal disorders Abdominal pain	3.4% 1/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	16.1% 5/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Gastrointestinal disorders Colitis	3.4% 1/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	9.7% 3/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Gastrointestinal disorders Colitis ulcerative	3.4% 1/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	9.7% 3/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Gastrointestinal disorders Constipation	0.00% 0/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	9.7% 3/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Gastrointestinal disorders Dry mouth	13.8% 4/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	0.00% 0/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Gastrointestinal disorders Nausea	27.6% 8/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	9.7% 3/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Gastrointestinal disorders Vomiting	13.8% 4/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	0.00% 0/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
General disorders Fatigue	13.8% 4/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	12.9% 4/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Infections and infestations Lower respiratory tract infection	10.3% 3/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	0.00% 0/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Infections and infestations Nasopharyngitis	6.9% 2/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	3.2% 1/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Infections and infestations Upper respiratory tract infection	6.9% 2/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	0.00% 0/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	9.7% 3/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Musculoskeletal and connective tissue disorders Muscle twitching	6.9% 2/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	0.00% 0/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Nervous system disorders Disturbance in attention	17.2% 5/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	0.00% 0/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Nervous system disorders Dizziness	41.4% 12/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	9.7% 3/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Nervous system disorders Headache	13.8% 4/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	12.9% 4/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Nervous system disorders Lethargy	6.9% 2/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	6.5% 2/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Nervous system disorders Memory impairment	10.3% 3/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	0.00% 0/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Nervous system disorders Somnolence	34.5% 10/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	6.5% 2/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Psychiatric disorders Disorientation	13.8% 4/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	0.00% 0/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.
Skin and subcutaneous tissue disorders Rash	0.00% 0/29 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.	9.7% 3/31 • Post-dose on Day 1 through 14 days after the final dose (up to 85 days). Safety analysis set: All randomized participants who received at least one dose of study drug and were analyzed according to the treatment received.