A Randomized Controlled Trial of Cannabidiol (GWP42003-P,... | NCT02544763

ID	Type	Description	Link
2015-002154-12	EudraCT Number

Label	Type	Description	Intervention Names
25 mg/kg/day GWP42003-P	Experimental	100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).	Drug: GWP42003-P
50 mg/kg/day GWP42003-P	Experimental	100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).	Drug: GWP42003-P
Placebo	Placebo Comparator	Placebo oral solution matching 100 mg/mL GWP42003-P.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
GWP42003-P	Drug	Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Measure	Description	Time Frame
Percent Change From Baseline in the Number of Tuberous Sclerosis Complex (TSC)-Associated Seizures During the Treatment Period (Maintenance and Titration)	TSC-associated seizures included: focal motor seizures without impairment of consciousness or awareness (Type 1 focal motor); focal seizures with impairment of consciousness or awareness (Type 2 focal); focal seizures evolving to bilateral generalized convulsive seizures (Type 3 focal); and tonic-clonic, tonic, clonic, or atonic seizures that are countable. Percent change from Baseline was calculated as the (post-Baseline value minus the Baseline value) divided by the Baseline value x 100.	Baseline; up to Week 16

Measure	Description	Time Frame
Number of Participants Considered Treatment Responders During the Treatment Period (Maintenance and Titration)	Treatment responders are defined as those participants with a ≥ 50% reduction in TSC-associated seizure frequency. TSC-associated seizures included: focal motor seizures without impairment of consciousness or awareness (Type 1 focal motor); focal seizures with impairment of consciousness or awareness (Type 2 focal); focal seizures evolving to bilateral generalized convulsive seizures (Type 3 focal); and tonic-clonic, tonic, clonic, or atonic seizures that are countable. Participants who withdrew from the trial during the treatment period are considered non-responders.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Participant has a well-documented clinical history of epilepsy.
Participant has a clinical diagnosis of Tuberous Sclerosis Complex (TSC) according to the criteria agreed by the 2012 International TSC Consensus Conference.
All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must have been stable for 1 month prior to screening and the participant is willing to maintain a stable regimen throughout the trial.

Key Exclusion Criteria:

Participant has a history of pseudo-seizures.
Participant has clinically significant unstable medical conditions other than epilepsy.
Participant has an illness in the 4 weeks prior to screening or randomization, other than epilepsy, which in the opinion of the investigator could affect seizure frequency.
Participant has undergone general anesthetic in the 4 weeks prior to screening or randomization.
Participant has undergone surgery for epilepsy in the 6 months prior to screening.
Participant is being considered for epilepsy surgery or any procedure involving general anesthesia.
Participant has been taking felbamate for less than 1 year prior to screening.
Participant is taking an oral mTOR inhibitor.
Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), such as sesame oil.
Participant has any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the C-SSRS in the last month or at screening.
Participant is currently using or has in the past used recreational or medicinal cannabis, or cannabinoid-based medications, within the 3 months prior to screening and is unwilling to abstain for the duration for the study.
Participant has tumor growth which, in the opinion of the Investigator, could affect the primary endpoint.
Participant has significantly impaired hepatic function at the screening or randomization visit
Participant has received an IMP within the 12 weeks prior to the screening visit.

Facility	Status	City	State	ZIP	Country	Contacts
UAB Epilepsy Center		Birmingham	Alabama	35294	United States
Arkansas Children's Hospital

PubMed Identifier	Type	Citation	Retractions
38441854	Derived	Burke C, Crossan C, Tyas E, Hemstock M, Lee D, Bowditch S. A Cost-Utility Analysis of Add-On Cannabidiol Versus Usual Care Alone for the Treatment of Seizures Associated with Tuberous Sclerosis Complex in England and Wales. Pharmacoecon Open. 2024 Jul;8(4):611-626. doi: 10.1007/s41669-024-00474-x. Epub 2024 Mar 5.
35175622	Derived

ID	Title	Description
FG000	GWP42003-P 25 mg/kg/Day	Participants were randomized to receive GWP42003-P 25 milligrams per kilogram per day (mg/kg/day) (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 23, 2019	Aug 26, 2020

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Two participants were excluded from the summary of demographic data because their heights at screening were measured in inches but were recorded in centimeters.

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG00075 ParticipantsBG00172 ParticipantsBG00275 ParticipantsBG003

Sex: Female, Male

Two participants were excluded from the summary of demographic data because their heights at screening were measured in inches but were recorded in centimeters.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00075 ParticipantsBG00172 ParticipantsBG002

Race/Ethnicity, Customized

Two participants were excluded from the summary of demographic data because their heights at screening were measured in inches but were recorded in centimeters.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00075 ParticipantsBG00172 ParticipantsBG002

Number of Tuberous Sclerosis Complex (TSC)-Associated Seizures

TSC-associated seizures included: focal motor seizures without impairment of consciousness or awareness (Type 1 focal motor); focal seizures with impairment of consciousness or awareness (Type 2 focal); focal seizures evolving to bilateral generalized convulsive seizures (Type 3 focal); and tonic-clonic, tonic, clonic, or atonic seizures that are countable.

Intent-to-Treat (ITT) Analysis Set: all participants who were randomized and dosed with IMP in the trial and had post-Baseline efficacy data. Participant data were analyzed according to the treatment group to which they were randomized.

Mean

Standard Deviation

seizures

Title	Denominators	Categories
	ParticipantsBG00075 ParticipantsBG001

Number of Total Seizures

Total seizures included all seizure types combined. The Baseline Period included all data prior to Day 1.

ITT Analysis Set

Mean

Standard Deviation

seizures

Title	Denominators	Categories
	ParticipantsBG00075 ParticipantsBG00173 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change From Baseline in the Number of Tuberous Sclerosis Complex (TSC)-Associated Seizures During the Treatment Period (Maintenance and Titration)

Intent-to-Treat (ITT) Analysis Set: all participants who were randomized and dosed with investigational medicinal product (IMP) in the trial and had post-Baseline efficacy data. Participant data were analyzed according to the treatment group to which they were randomized.

Posted

Median

Inter-Quartile Range

percent change

Baseline; up to Week 16

ID	Title	Description
OG000	GWP42003-P 25 mg/kg/Day	Participants were randomized to receive GWP42003-P 25 milligrams per kilogram per day (mg/kg/day) (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.
OG001	GWP42003-P 50 mg/kg/Day	Participants were randomized to receive GWP42003-P 50 mg/kg/day (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.
OG002	Placebo	Participants were randomized to receive placebo matched to GWP42003-P (via oral twice daily [morning and evening] administration) for 16 weeks.

Units	Counts
Participants	OG00075 OG00173 OG00276

Title

Denominators

Categories

Title	Measurements
	OG000-43.36(-67.8 to -13.6) OG001-36.55(-67.0 to -5.5) OG002-20.08(-47.1 to 3.1)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000						Percentage reduction	48.6			2-Sided	95	40.4	55.8					Superiority
OG001						Percentage reduction

Secondary

Number of Participants Considered Treatment Responders During the Treatment Period (Maintenance and Titration)

Treatment responders are defined as those participants with a ≥ 50% reduction in TSC-associated seizure frequency. TSC-associated seizures included: focal motor seizures without impairment of consciousness or awareness (Type 1 focal motor); focal seizures with impairment of consciousness or awareness (Type 2 focal); focal seizures evolving to bilateral generalized convulsive seizures (Type 3 focal); and tonic-clonic, tonic, clonic, or atonic seizures that are countable. Participants who withdrew from the trial during the treatment period are considered non-responders.

ITT Analysis Set

Posted

Count of Participants

Participants

Baseline; up to Week 16

ID	Title	Description
OG000	GWP42003-P 25 mg/kg/Day	Participants were randomized to receive GWP42003-P 25 milligrams per kilogram per day (mg/kg/day) (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.
OG001	GWP42003-P 50 mg/kg/Day	Participants were randomized to receive GWP42003-P 50 mg/kg/day (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.

Secondary

Change From Baseline in the Caregiver Global Impression of Change (CGIC) or Participant Global Impression of Change (PGIC) Score at the Participant's Last Visit

The combined caregiver and participant summary uses either the caregiver or participant version if only one version was completed, or the caregiver version if both caregiver and participant versions were completed. The CGIC comprised the following question, to be rated on a 7-point scale (1, Very Much Improved; 2, Much Improved; 3, Slightly Improved; 4, No Change; 5, Slightly Worse; 6, Much Worse; 7, Very Much Worse): "Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment)." The SGIC comprised the following question, to be rated on a 7-point scale (1, Very Much Improved; 2, Much Improved; 3, Slightly Improved; 4, No Change; 5, Slightly Worse; 6, Much Worse; 7, Very Much Worse): "Since you started treatment, please assess the status of your overall condition (comparing your condition now to your condition before treatment)."

ITT Analysis Set. Only participants with available data were analyzed. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Posted

Mean

Standard Deviation

units on a scale

Baseline; up to Week 16

ID	Title	Description
OG000	GWP42003-P 25 mg/kg/Day	Participants were randomized to receive GWP42003-P 25 milligrams per kilogram per day (mg/kg/day) (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.

Secondary

Percent Change From Baseline in Total Seizures During the Treatment Period (Maintenance and Titration)

Total seizures included all seizure types combined. Percent change from Baseline was calculated as the (post-Baseline value minus the Baseline value) divided by the Baseline value x 100.

ITT Analysis Set

Posted

Mean

Standard Deviation

percent change

Baseline; up to Week 16

ID	Title	Description
OG000	GWP42003-P 25 mg/kg/Day	Participants were randomized to receive GWP42003-P 25 milligrams per kilogram per day (mg/kg/day) (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.
OG001	GWP42003-P 50 mg/kg/Day	Participants were randomized to receive GWP42003-P 50 mg/kg/day (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.
OG002	Placebo	Participants were randomized to receive placebo matched to GWP42003-P (via oral twice daily [morning and evening] administration) for 16 weeks.

Secondary

Number of Participants With Any Severe Treatment-emergent Adverse Event (TEAE)

A TEAE was defined as an AE with a start date on or after the first dose of IMP during the Blinded Phase up to and including the date of first dose of the Open-label Extension (OLE) Phase (OLE Day 1).

Safety Analysis Set: all participants randomized to treatment who received at least 1 dose of IMP

Posted

Count of Participants

Participants

up to approximately Week 22

ID	Title	Description
OG000	GWP42003-P 25 mg/kg/Day	Participants were randomized to receive GWP42003-P 25 milligrams per kilogram per day (mg/kg/day) (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.
OG001	GWP42003-P 50 mg/kg/Day	Participants were randomized to receive GWP42003-P 50 mg/kg/day (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.
OG002	Placebo	Participants were randomized to receive placebo matched to GWP42003-P (via oral twice daily [morning and evening] administration) for 16 weeks.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vomiting	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Abdominal pain	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Diarrhoea	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Nausea	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Fatigue	General disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Malaise	General disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Liver injury	Hepatobiliary disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Type IV hypersensitivity reaction	Immune system disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Gastroenteritis viral	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Pneumonia	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0021 affected76 at risk
Gastroenteritis	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Otitis media acute	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Laceration	Injury, poisoning and procedural complications	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Alanine aminotransferase increased	Investigations	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Aspartate aminotransferase increased	Investigations	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Transaminases increased	Investigations	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Blood bilirubin increased	Investigations	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Dehydration	Metabolism and nutrition disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Hypophagia	Metabolism and nutrition disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Status epilepticus	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0021 affected76 at risk
Seizure	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Generalised tonic-clonic seizure	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Rash	Skin and subcutaneous tissue disorders	MedDra 19.1	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDra 19.1	Systematic Assessment	EG0005 affected75 at risk EG0013 affected73 at risk EG0021 affected76 at risk
Ear pain	Ear and labyrinth disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0013 affected73 at risk EG0021 affected76 at risk
Constipation	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG0008 affected75 at risk EG0015 affected73 at risk EG0026 affected76 at risk
Diarrhoea	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG00023 affected75 at risk EG00140 affected73 at risk EG00219 affected76 at risk
Frequent bowel movements	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Nausea	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG0006 affected75 at risk EG0012 affected73 at risk EG0022 affected76 at risk
Retching	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Vomiting	Gastrointestinal disorders	MedDra 19.1	Systematic Assessment	EG00012 affected75 at risk EG00113 affected73 at risk EG0027 affected76 at risk
Fatigue	General disorders	MedDra 19.1	Systematic Assessment	EG0003 affected75 at risk EG0014 affected73 at risk EG0021 affected76 at risk
Gait disturbance	General disorders	MedDra 19.1	Systematic Assessment	EG0004 affected75 at risk EG0013 affected73 at risk EG0022 affected76 at risk
Pyrexia	General disorders	MedDra 19.1	Systematic Assessment	EG00014 affected75 at risk EG00112 affected73 at risk EG0026 affected76 at risk
Bronchitis	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0011 affected73 at risk EG0021 affected76 at risk
Ear infection	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0014 affected73 at risk EG0020 affected76 at risk
Gastroenteritis	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0003 affected75 at risk EG0012 affected73 at risk EG0022 affected76 at risk
Gastroenteritis viral	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0013 affected73 at risk EG0023 affected76 at risk
Nasopharyngitis	Infections and infestations	MedDra 19.1	Systematic Assessment	EG00011 affected75 at risk EG00111 affected73 at risk EG00212 affected76 at risk
Otitis media	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Pharyngitis	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0012 affected73 at risk EG0022 affected76 at risk
Pharyngitis streptococcal	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected73 at risk EG0021 affected76 at risk
Pneumonia	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Respiratory tract infection	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0022 affected76 at risk
Tonsillitis	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0021 affected76 at risk
Upper respiratory tract infection	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0007 affected75 at risk EG0017 affected73 at risk EG00210 affected76 at risk
Urinary tract infection	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0004 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Viral infection	Infections and infestations	MedDra 19.1	Systematic Assessment	EG0003 affected75 at risk EG0010 affected73 at risk EG0022 affected76 at risk
Fall	Injury, poisoning and procedural complications	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0014 affected73 at risk EG0025 affected76 at risk
Laceration	Injury, poisoning and procedural complications	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0012 affected73 at risk EG0021 affected76 at risk
Alanine aminotransferase increased	Investigations	MedDra 19.1	Systematic Assessment	EG0007 affected75 at risk EG00114 affected73 at risk EG0020 affected76 at risk
Anticonvulsant drug level increased	Investigations	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0012 affected73 at risk EG0021 affected76 at risk
Aspartate aminotransferase increased	Investigations	MedDra 19.1	Systematic Assessment	EG0006 affected75 at risk EG00112 affected73 at risk EG0020 affected76 at risk
Eosinophil count increased	Investigations	MedDra 19.1	Systematic Assessment	EG0004 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk
Gamma-glutamyltransferase increased	Investigations	MedDra 19.1	Systematic Assessment	EG00012 affected75 at risk EG00110 affected73 at risk EG0020 affected76 at risk
Hepatic enzyme increased	Investigations	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0013 affected73 at risk EG0020 affected76 at risk
International normalised ratio increased	Investigations	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Platelet count decreased	Investigations	MedDra 19.1	Systematic Assessment	EG0003 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Prothrombin time prolonged	Investigations	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Weight decreased	Investigations	MedDra 19.1	Systematic Assessment	EG0005 affected75 at risk EG0016 affected73 at risk EG0020 affected76 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDra 19.1	Systematic Assessment	EG00015 affected75 at risk EG00117 affected73 at risk EG0029 affected76 at risk
Diet refusal	Metabolism and nutrition disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Increased appetite	Metabolism and nutrition disorders	MedDra 19.1	Systematic Assessment	EG0003 affected75 at risk EG0013 affected73 at risk EG0025 affected76 at risk
Ataxia	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0003 affected75 at risk EG0012 affected73 at risk EG0022 affected76 at risk
Dizziness	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0023 affected76 at risk
Drooling	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0012 affected73 at risk EG0022 affected76 at risk
Headache	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0004 affected75 at risk EG0012 affected73 at risk EG0024 affected76 at risk
Hypersomnia	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Lethargy	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0004 affected75 at risk EG0013 affected73 at risk EG0025 affected76 at risk
Seizure	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG0004 affected75 at risk EG0017 affected73 at risk EG0025 affected76 at risk
Somnolence	Nervous system disorders	MedDra 19.1	Systematic Assessment	EG00010 affected75 at risk EG00119 affected73 at risk EG0027 affected76 at risk
Abnormal behaviour	Psychiatric disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0012 affected73 at risk EG0021 affected76 at risk
Aggression	Psychiatric disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0012 affected73 at risk EG0023 affected76 at risk
Agitation	Psychiatric disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0012 affected73 at risk EG0023 affected76 at risk
Anxiety	Psychiatric disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0021 affected76 at risk
Insomnia	Psychiatric disorders	MedDra 19.1	Systematic Assessment	EG0003 affected75 at risk EG0012 affected73 at risk EG0025 affected76 at risk
Irritability	Psychiatric disorders	MedDra 19.1	Systematic Assessment	EG0004 affected75 at risk EG0015 affected73 at risk EG0024 affected76 at risk
Panic attack	Psychiatric disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDra 19.1	Systematic Assessment	EG0001 affected75 at risk EG0012 affected73 at risk EG0020 affected76 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDra 19.1	Systematic Assessment	EG0008 affected75 at risk EG0013 affected73 at risk EG0025 affected76 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDra 19.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected73 at risk EG0021 affected76 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDra 19.1	Systematic Assessment	EG0003 affected75 at risk EG0013 affected73 at risk EG0020 affected76 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0011 affected73 at risk EG0021 affected76 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0010 affected73 at risk EG0020 affected76 at risk
Rash	Skin and subcutaneous tissue disorders	MedDra 19.1	Systematic Assessment	EG0003 affected75 at risk EG0017 affected73 at risk EG0022 affected76 at risk
Hypertension	Vascular disorders	MedDra 19.1	Systematic Assessment	EG0002 affected75 at risk EG0011 affected73 at risk EG0020 affected76 at risk

ID	Term
D006222	Hamartoma
D009369	Neoplasms
D009378	Neoplasms, Multiple Primary
D009386	Neoplastic Syndromes, Hereditary
D065703	Malformations of Cortical Development, Group I
D054220	Malformations of Cortical Development
D009421	Nervous System Malformations
D009422	Nervous System Diseases
D020752	Neurocutaneous Syndromes
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342	Genetic Diseases, Inborn
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D002186	Cannabinoids
D013729	Terpenes
D006838	Hydrocarbons
D009930	Organic Chemicals

ID	Title	Description
BG000	GWP42003-P 25 mg/kg/Day	Participants were randomized to receive GWP42003-P 25 milligrams per kilogram per day (mg/kg/day) (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.
BG001	GWP42003-P 50 mg/kg/Day	Participants were randomized to receive GWP42003-P 50 mg/kg/day (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.
BG002	Placebo	Participants were randomized to receive placebo matched to GWP42003-P (via oral twice daily [morning and evening] administration) for 16 weeks.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	GWP42003-P 25 mg/kg/Day	Participants were randomized to receive GWP42003-P 25 milligrams per kilogram per day (mg/kg/day) (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.	75	16	75	66	75
EG001	GWP42003-P 50 mg/kg/Day	Participants were randomized to receive GWP42003-P 50 mg/kg/day (via oral twice daily [morning and evening] administration). Participants completed a 4-week dose escalation period, titrating up to their assigned dose, before continuing on a stable dose of blinded GWP42003-P for 12 weeks.	73	10	73	71	73
EG002	Placebo	Participants were randomized to receive placebo matched to GWP42003-P (via oral twice daily [morning and evening] administration) for 16 weeks.	76	2	76	68	76