Trial Outcomes & Findings for GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome (NCT NCT02224703)

Last Updated: 2022-09-28

Results Overview

Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

199 participants

Primary outcome timeframe

Baseline to Day 99 or Early Termination (ET)

Results posted on

2022-09-28

Participant Flow

A total of 43 sites screened participants and 38 sites (23 in the United States, 7 in Spain, 3 in Poland, 2 in Australia, 1 in Israel, and 2 in the Netherlands) randomized participants into the trial. Two sites selected (1 in Israel and 1 in the United States) did not screen any participants.

To assess eligibility, participants, 2-18 years of age with Dravet syndrome had to be taking 1 or more antiepileptic drugs at a dose which had been stable; and medicated for epilepsy for at least 4 weeks were screened. A total of 285 participants were screened, of which 199 were randomized.

Participant milestones

Participant milestones
Measure	10 mg/kg/Day GWP42003-P GWP42003-P oral solution (100 milligrams/milliliter \[mg/mL\] cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kilogram (kg)/day dose was defined as 50% of the 20 mg/kg/day dose.	20 mg/kg/Day GWP42003-P GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring).The 20 mg/kg/day dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).	Placebo Control Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
Overall Study STARTED	67	67	65
Overall Study Received at Least 1 Dose of Study Drug	66	67	65
Overall Study Safety Analysis Set	64	69	65
Overall Study Intent to Treat (ITT) Analysis Set	66	67	65
Overall Study COMPLETED	64	61	65
Overall Study NOT COMPLETED	3	6	0

Reasons for withdrawal

Reasons for withdrawal
Measure	10 mg/kg/Day GWP42003-P GWP42003-P oral solution (100 milligrams/milliliter \[mg/mL\] cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kilogram (kg)/day dose was defined as 50% of the 20 mg/kg/day dose.	20 mg/kg/Day GWP42003-P GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring).The 20 mg/kg/day dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).
Overall Study Adverse Event	0	5
Overall Study Withdrawn by investigator	1	0
Overall Study Advised by medical monitor	1	0
Overall Study Withdrawn by parent/guardian	0	1
Overall Study Lack of Efficacy	1	0

Baseline Characteristics

GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	10 mg/kg/Day GWP42003-P n=64 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 10 mg/kg/day dose.	20 mg/kg/Day GWP42003-P n=69 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).	Placebo Control n=65 Participants Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.	Total n=198 Participants Total of all reporting groups
Age, Continuous	9.169 Years STANDARD_DEVIATION 4.1744 • n=5 Participants	9.245 Years STANDARD_DEVIATION 4.3792 • n=7 Participants	9.617 Years STANDARD_DEVIATION 4.5757 • n=5 Participants	9.343 Years STANDARD_DEVIATION 4.3626 • n=4 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	32 Participants n=7 Participants	34 Participants n=5 Participants	104 Participants n=4 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	37 Participants n=7 Participants	31 Participants n=5 Participants	94 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized White	55 Participants n=5 Participants	66 Participants n=7 Participants	55 Participants n=5 Participants	176 Participants n=4 Participants
Race/Ethnicity, Customized Other	8 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	11 Participants n=4 Participants
Region of Enrollment Australia	6 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	13 participants n=4 Participants
Region of Enrollment Israel	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment Netherlands	9 participants n=5 Participants	7 participants n=7 Participants	9 participants n=5 Participants	25 participants n=4 Participants
Region of Enrollment Poland	8 participants n=5 Participants	11 participants n=7 Participants	6 participants n=5 Participants	25 participants n=4 Participants
Region of Enrollment Spain	12 participants n=5 Participants	14 participants n=7 Participants	13 participants n=5 Participants	39 participants n=4 Participants
Region of Enrollment United States	29 participants n=5 Participants	32 participants n=7 Participants	32 participants n=5 Participants	93 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Day 99 or Early Termination (ET)

Population: Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.

Outcome measures

Outcome measures
Measure	10 mg/kg/Day GWP42003-P n=66 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.	20 mg/kg/Day GWP42003-P n=67 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).	Placebo Control n=65 Participants Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
Change In Convulsive Seizures During The Treatment Period Compared To Baseline	48.7 percentage reduction Interval 37.9 to 57.6	45.7 percentage reduction Interval 34.2 to 55.2	26.9 percentage reduction Interval 11.9 to 39.4

SECONDARY outcome

Timeframe: Baseline to Day 99 or ET

Population: Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.

Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.

Outcome measures

Outcome measures
Measure	10 mg/kg/Day GWP42003-P n=66 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.	20 mg/kg/Day GWP42003-P n=67 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).	Placebo Control n=65 Participants Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
Change In Total Seizures During The Treatment Period Compared To Baseline	56.4 percentage reduction Interval 47.8 to 63.6	47.3 percentage reduction Interval 36.9 to 56.0	29.7 percentage reduction Interval 16.0 to 41.1

SECONDARY outcome

Timeframe: Baseline to Day 99 or ET

Population: Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.

Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: (\[frequency during the treatment period - frequency during baseline\]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).

Outcome measures

Outcome measures
Measure	10 mg/kg/Day GWP42003-P n=66 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.	20 mg/kg/Day GWP42003-P n=67 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).	Placebo Control n=65 Participants Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period	29 Participants	33 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline to Last Visit

Population: Intention-to-treat (ITT) analysis set: All participants who were randomized and dosed in the trial and had post-baseline efficacy data.

On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-point scale: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The markers were: "Very Much Improved"; "Much Improved"; "Slightly Improved"; "No Change"; "Slightly Worse"; "Much Worse"; "Very Much Worse". The CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.

Outcome measures

Outcome measures
Measure	10 mg/kg/Day GWP42003-P n=66 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.	20 mg/kg/Day GWP42003-P n=66 Participants GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).	Placebo Control n=65 Participants Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
Caregiver Global Impression Of Change (CGIC) At The Last Visit Very Much Improved	13 Participants	11 Participants	1 Participants
Caregiver Global Impression Of Change (CGIC) At The Last Visit Much Improved	11 Participants	10 Participants	8 Participants
Caregiver Global Impression Of Change (CGIC) At The Last Visit Slightly Improved	21 Participants	19 Participants	18 Participants
Caregiver Global Impression Of Change (CGIC) At The Last Visit No Change	18 Participants	17 Participants	32 Participants
Caregiver Global Impression Of Change (CGIC) At The Last Visit Slightly Worse	2 Participants	5 Participants	4 Participants
Caregiver Global Impression Of Change (CGIC) At The Last Visit Much Worse	1 Participants	3 Participants	2 Participants
Caregiver Global Impression Of Change (CGIC) At The Last Visit Very Much Worse	0 Participants	1 Participants	0 Participants

Adverse Events

10 mg/kg/Day GWP42003-P

Serious events: 13 serious events

Other events: 56 other events

Deaths: 0 deaths

20 mg/kg/Day GWP42003-P

Serious events: 17 serious events

Other events: 60 other events

Deaths: 0 deaths

Placebo Control

Serious events: 10 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Enquiries

GW Research Ltd

Phone: +44 01223 238170; +18778862810

Email: [email protected]; [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	10 mg/kg/Day GWP42003-P n=64 participants at risk GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 10 mg/kg/day dose.	20 mg/kg/Day GWP42003-P n=69 participants at risk GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).	Placebo Control n=65 participants at risk Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
Gastrointestinal disorders Diarrhoea	17.2% 11/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	26.1% 18/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	12.3% 8/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Gastrointestinal disorders Vomiting	6.2% 4/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	15.9% 11/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	6.2% 4/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
General disorders Pyrexia	23.4% 15/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	20.3% 14/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	16.9% 11/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
General disorders Fatigue	7.8% 5/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	20.3% 14/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	10.8% 7/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Infections and infestations Nasopharyngitis	6.2% 4/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	11.6% 8/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	7.7% 5/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Infections and infestations Upper respiratory tract infection	4.7% 3/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	5.8% 4/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	4.6% 3/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Infections and infestations Urinary tract infection	0.00% 0/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	5.8% 4/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	1.5% 1/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Injury, poisoning and procedural complications Toxicity to various agents	1.6% 1/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	5.8% 4/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	0.00% 0/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Investigations Alanine aminotransferase increased	4.7% 3/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	11.6% 8/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	0.00% 0/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Investigations Aspartate aminotransferase increased	4.7% 3/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	11.6% 8/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	0.00% 0/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Investigations Gamma-glutamyltransferase increased	6.2% 4/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	5.8% 4/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	4.6% 3/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Metabolism and nutrition disorders Decreased appetite	15.6% 10/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	27.5% 19/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	16.9% 11/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Nervous system disorders Somnolence	21.9% 14/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	23.2% 16/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	13.8% 9/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Nervous system disorders Convulsion	4.7% 3/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	5.8% 4/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	6.2% 4/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Nervous system disorders Tremor	0.00% 0/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	5.8% 4/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	0.00% 0/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Psychiatric disorders Aggression	1.6% 1/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	8.7% 6/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	3.1% 2/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Psychiatric disorders Irritability	4.7% 3/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	7.2% 5/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	3.1% 2/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Psychiatric disorders Abnormal behaviour	0.00% 0/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	5.8% 4/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	0.00% 0/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/64 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	1.4% 1/69 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.	6.2% 4/65 • From Day 1 to Day 137. Safety Analysis Set: Received at least 1 dose of study drug and were analyzed per treatment received. Two participants randomized to receive GWP42003-P 10 mg/kg/day titrated above the target dose and were therefore assigned to the GWP42003-P 20 mg/kg/day group for all safety analyses.