Efficacy and Safety of Cannabidiol Oral Solution (GWP4200... | NCT03848832

NCT03848832

ID	Type	Description	Link
2018-003370-27	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
5 milligrams per kilogram per day (mg/kg/day) GWP42003-P	Experimental	100 milligrams per milliliter (mg/mL) GWP42003-P oral solution. Taken twice daily (morning and evening).	Drug: GWP42003-P
15 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 (0 mg/mL GWP42003-P) volume matched to 5 mg/kg/day or 15 mg/kg/day GWP42003-P. Taken twice daily (morning and evening).	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GWP42003-P	Drug	GWP42003-P presented as an oral solution containing cannabidiol	15 mg/kg/day GWP42003-P 5 milligrams per kilogram per day (mg/kg/day) GWP42003-P

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Mean Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score at Week 24 for the 15 mg/kg/Day GWP42003-P Dose Level Compared With Placebo	RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics (45 items) in individuals with Rett Syndrome. Each item is rated on a 3-point scale (0-2); 0 indicating an item that is "not true as far as you know," 1 indicating an item is "somewhat or sometimes true," and 2 indicating an item that is "very true or often true." Item 31 ("Uses eye gaze to convey feelings, needs and wishes") is reverse scored (0 indicating "very true or often true", 1 indicating "somewhat or sometimes true," and 2 indicating "not true as far as you know"). The total summed score ranges from 0 to 90, with higher scores representing greater severity.	Baseline; Week 24

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Mean RSBQ Total Score at Week 24 for the 5 mg/kg/Day GWP42003-P Dose Level Compared With Placebo	RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics (45 items) in individuals with Rett Syndrome. Each item is rated on a 3-point scale (0-2); 0 indicating an item that is "not true as far as you know," 1 indicating an item is "somewhat or sometimes true," and 2 indicating an item that is "very true or often true." Item 31 ("Uses eye gaze to convey feelings, needs and wishes") is reverse scored (0 indicating "very true or often true", 1 indicating "somewhat or sometimes true," and 2 indicating "not true as far as you know"). The total summed score ranges from 0 to 90, with higher scores represent greater severity.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Participant (if possessing adequate understanding, in the investigator's opinion) and/or their parent(s)/legal representative is willing and able to give informed consent/assent for participation in the trial.
Participant and their caregiver are willing and able (in the investigator's opinion) to comply with all trial requirements (including the completion of all caregiver assessments by the same caregiver throughout the trial).
Participant must weigh at least 10 kilograms.
Clinical diagnosis of Rett syndrome (typical or atypical), defined according to RettSearch Consortium criteria
Confirmed pathogenic genetic mutation of the MECP2 gene
Participant must be post-regression (≥ 6 months since last loss of hand use or verbal language or gross motor regression).
Participant must have a disease severity of between 10 and 36, defined according to the Clinical Severity Scale (CSS).
All medications or interventions (including antiepileptic drugs [AEDs] and non-pharmacological interventions - dietary supplements, probiotics, physical therapy, speech therapy, etc.) for Rett syndrome-related symptoms must have been stable for 4 weeks prior to screening and the participant/caregiver must be willing to maintain a stable regimen throughout the trial.
Ability to swallow the investigational medicinal product (IMP) provided as a liquid solution, or the ability for IMP to be delivered via gastrostomy (G) or nasogastric (NG) feeding tube (only G-or NG-tubes made from polyurethane or silicon are allowed)
Participant and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law.
Participant and/or parent(s)/legal representative is willing to allow the participant's primary care practitioner (if they have one) and consultant (if they have one) to be notified of participation in the trial, if the primary care practitioner/consultant is different than the investigator.

Key Exclusion Criteria:

Participant meets exclusion criteria for Rett syndrome diagnosis (traumatic brain injury, neurometabolic disease, or severe infection that causes neurological problems; grossly abnormal psychomotor development in the first 6 months of life).
Participant has clinically significant abnormal laboratory values, in the investigator's opinion.
Participant is taking more than 2 concurrent AEDs.
Any history of suicidal behavior or any suicidal ideation in the last month or at screening
Clinically relevant abnormalities in the electrocardiogram (ECG) measured at screening or randomization
Concurrent cardiovascular conditions which will, in the investigator's opinion, interfere with the ability to assess their ECGs or put the participant at risk because of participation in the trial
First or second degree relative with a history of significant ECG abnormalities, in the opinion of the investigator (e.g. premature cardiac arrest, sudden death)
Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP (active or placebo), such as sesame oil
Participant has moderately impaired hepatic function at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) or total bilirubin > 2 × ULN.
Participant is of childbearing potential, unless willing to ensure that they or their partner use a highly effective method of birth control (e.g., combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, or transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, or implantable], intrauterine devices/hormone-releasing systems, bilateral tubal occlusion, vasectomized partner, sexual abstinence) during the trial and for 3 months thereafter.
Pregnant (positive pregnancy test) or lactating
Received an IMP within the 3 months prior to screening
Participant has been taking felbamate for less than 1 year prior to screening.
Currently using or has used recreational or medicinal cannabis, cannabinoid-based medications (including Sativex®), or cannabidiol oral solutions (including CBD-OS [GWP42003-P]) within the 3 months prior to screening and is unwilling to abstain for the duration of the trial
Participant has a positive delta-9-tetrahydrocannabinol (THC) test at screening.
Any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory) or significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the trial, may influence the result of the trial, or the participant's ability to participate in the trial
Any abnormalities identified following a physical examination of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if she took part in the trial
Participant has been previously randomized into this trial.
Participant has traveled outside the country of residence planned during the trial.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Trial Site		Birmingham	Alabama	35294-0021	United States
Clinical Trial Site

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	5 mg/kg/Day GWP42003-P	Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID).
FG001	15 mg/kg/Day GWP42003-P

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 7, 2020	Sep 28, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID.

One participant assigned to the 5 mg/kg/Day placebo group was misdosed with 5 mg/kg/Day GWP42003-P. The participant was included in the 5 mg/kg/Day placebo group in the Intent-to-Treat Set but was included in the 5 mg/kg/day GWP42003-P group in the Safety Analysis Set (for which Baseline data are reported).

Arm/Group Information

ID	Title	Description
BG000	5 mg/kg/Day GWP42003-P	Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID).
BG001	15 mg/kg/Day GWP42003-P	Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID.
BG002	Placebo	Participants received placebo oral solution matched to 5 or 15 mg/kg/day GWP42003-P, BID.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG00011 BG0019 BG0029 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0009.7± 6.02 BG00110.7± 3.64 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00011 BG0019 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0010 BG002

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

Change From Baseline in the Mean Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score at Week 24 for the 15 mg/kg/Day GWP42003-P Dose Level Compared With Placebo

RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics (45 items) in individuals with Rett Syndrome. Each item is rated on a 3-point scale (0-2); 0 indicating an item that is "not true as far as you know," 1 indicating an item is "somewhat or sometimes true," and 2 indicating an item that is "very true or often true." Item 31 ("Uses eye gaze to convey feelings, needs and wishes") is reverse scored (0 indicating "very true or often true", 1 indicating "somewhat or sometimes true," and 2 indicating "not true as far as you know"). The total summed score ranges from 0 to 90, with higher scores representing greater severity.

Intent-to-Treat (ITT) Set: All randomized participants who received at least 1 dose of drug in the trial, and had Baseline efficacy data. Participants with non-missing data were included for analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline; Week 24

ID	Title	Description
OG000	15 mg/kg/Day GWP42003-P	Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID.
OG001	Placebo	Participants received placebo oral solution matched to 5 or 15 mg/kg/day GWP42003-P, BID.

Units	Counts
Participants	OG0009 OG00110

Title

Denominators

Categories

Baseline

- ParticipantsOG0009
- ParticipantsOG00110

Title	Measurements
	OG00045.9± 16.77

Secondary

Change From Baseline in the Mean RSBQ Total Score at Week 24 for the 5 mg/kg/Day GWP42003-P Dose Level Compared With Placebo

ITT Set. Participants with non-missing data were included for analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline; Week 24

ID	Title	Description
OG000	5 mg/kg/Day GWP42003-P	Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID).
OG001	Placebo	Participants received placebo oral solution matched to 5 or 15 mg/kg/day GWP42003-P, BID.

Secondary

Mean Clinical Global Impressions - Improvement (CGI-I) Score at Week 24

CGI-I is a 7-point scale that requires the clinician to assess how much a participant's illness has improved or worsened relative to a Baseline state at the beginning of the intervention. This is rated as: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse.

ITT Set. Participants with non-missing data were included for analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline; Week 24

ID	Title	Description
OG000	5 mg/kg/Day GWP42003-P	Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID).
OG001	15 mg/kg/Day GWP42003-P	Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID.
OG002	Placebo	Participants received placebo oral solution matched to 5 or 15 mg/kg/day GWP42003-P, BID.

Secondary

Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24

CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment relative to the clinician's experience with participants who had the same diagnosis. This is rated as: 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill.

ITT Set. Participants with non-missing data were included for analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline; Week 24

ID	Title	Description
OG000	5 mg/kg/Day GWP42003-P	Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID).
OG001	15 mg/kg/Day GWP42003-P	Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID.
OG002	Placebo	Participants received placebo oral solution matched to 5 or 15 mg/kg/day GWP42003-P, BID.

Secondary

Change From Baseline in Mean RSBQ Subscale Scores at Week 24

RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics in individuals with Rett Syndrome. The 45-item RSBQ is comprised of 8 subscales: 1) general mood (score range 0-16), 2) breathing problems (range 0-10), 3) hand behaviors (range 0-12), 4) face movements (range 0-8), 5) body rocking (BR)/expressionless face (range 0-12), 6) night-time behaviors (range 0-6), 7) anxiety/fear (range 0-8), 8) walking/standing (range 0-4). Each item is rated on a 3-point scale (0-2); 0 indicating an item that is "not true as far as you know," 1 indicating an item is "somewhat or sometimes true," and 2 indicating an item that is "very true or often true." Item 31 ("Uses eye gaze to convey feelings, needs and wishes") is reverse scored (0 indicating "very true or often true", 1 indicating "somewhat or sometimes true," and 2 indicating "not true as far as you know"). Higher scores representing greater severity. CFB = Change from Baseline.

ITT Set. Participants with non-missing data were included for analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline; Week 24

ID	Title	Description
OG000	5 mg/kg/Day GWP42003-P	Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID).
OG001	15 mg/kg/Day GWP42003-P	Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID.

Secondary

Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24

MBA-9 is derived from the full MBA scale (37 Rett syndrome symptoms) by selecting the items deemed amenable to change and which reflected areas of meaningful clinical change. the MBA-9 includes 9 items (1-Regression of motor skills; 2-Poor eye/social contact; 3-Lack of sustained interest; 4-Does not reach for objects or people; 5-Chewing difficulties; 6-Speech disturbance; 7-Hand clumsiness; 8-Dystonia and 9-Hypertonia/rigidity); for each item, the severity of current symptoms is rated by the investigator on a 5-point numerical scale ranging from 0 to 4 with higher scores representing greater severity (0 = normal or never; 1 = mild or rare; 2 = moderate or occasional; 3 = marked or frequent; 4 = very severe or constant). Total MBA-9 score was calculated by summing the scores of 9 different subscale items. The total summed score ranges from 0 to 36, with higher scores representing greater severity. CFB = Change from Baseline.

ITT Set. Participants with non-missing data were included for analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline; Week 24

ID	Title	Description
OG000	5 mg/kg/Day GWP42003-P	Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID).
OG001	15 mg/kg/Day GWP42003-P	Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID.

Secondary

Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24

CSHQ is a caregiver-completed sleep screening instrument designed for school-aged children; which includes 33 items within 8 subscales: 1) bedtime resistance (score range 6-18), 2) sleep onset delay (range 1-3), 3) sleep duration (range 3-9), 4) sleep anxiety (range 4-12), 5) night wakings (range 3-9), 6) parasomnias (range 7-21), 7) sleep-disordered breathing (range 3-9), 8) daytime sleepiness (range 8-24). Item scores range from 1 to 3, where 3="usually" (≥5 times/week), 2="sometimes" (2-4 times/week), and 1="rarely" (≤1 time/week); for items 31 and 32; 3=fall asleep, 2=very sleepy, 1=not sleepy. In general, a score of 3 indicates greater severity, however, 6 items (1-Goes to bed at same time; 2-Falls asleep in 20 minutes; 3-Falls asleep in own bed; 10-Sleeps the right amount; 11-Sleeps same amount each day; 26-Wakes by himself) are reverse scored. Total summed score ranges from 33 to 99, with higher scores representing more disturbed sleep behavior. CFB = Change from Baseline.

ITT Set. Participants with non-missing data were included for analysis.

Posted

Mean

Standard Deviation

units on a scale

Baseline; Week 24

ID	Title	Description
OG000	5 mg/kg/Day GWP42003-P	Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID).
OG001	15 mg/kg/Day GWP42003-P

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	5 mg/kg/Day GWP42003-P	Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID).	11	2	11	9	11
EG001	15 mg/kg/Day GWP42003-P	Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID.	9	2	9	7	9
EG002	Placebo	Participants received placebo oral solution matched to 5 or 15 mg/kg/day GWP42003-P, BID.	9	1	9	7	9

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
COVID-19	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0011 events1 affected9 at risk EG0021 events1 affected9 at risk
Lower respiratory tract infection	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Alanine aminotransferase increased	Investigations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Aspartate aminotransferase increased	Investigations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Dyskinesia	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coagulopathy	Blood and lymphatic system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Macrocytosis	Blood and lymphatic system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Neutropenia	Blood and lymphatic system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Ocular hyperaemia	Eye disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Abdominal pain	Gastrointestinal disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Constipation	Gastrointestinal disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Diarrhoea	Gastrointestinal disorders	MedDra 21.1	Systematic Assessment	EG0002 events2 affected11 at risk EG0012 events2 affected9 at risk EG0020 events0 affected9 at risk
Faeces soft	Gastrointestinal disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Tooth discolouration	Gastrointestinal disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Vomiting	Gastrointestinal disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0013 events2 affected9 at risk EG0020 events0 affected9 at risk
Fatigue	General disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Pyrexia	General disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0013 events2 affected9 at risk EG0021 events1 affected9 at risk
Gastroenteritis	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Nasopharyngitis	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0002 events2 affected11 at risk EG0010 events0 affected9 at risk EG0022 events1 affected9 at risk
Otitis media	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Pharyngitis streptococcal	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Upper respiratory tract infection	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0025 events3 affected9 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDra 21.1	Systematic Assessment	EG0004 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Sunburn	Injury, poisoning and procedural complications	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Alanine aminotransferase increased	Investigations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Aspartate aminotransferase increased	Investigations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Blood thyroid stimulating hormone increased	Investigations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Breath sounds abnormal	Investigations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Gamma-glutamyltransferase increased	Investigations	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Mean cell volume increased	Investigations	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0012 events2 affected9 at risk EG0020 events0 affected9 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Selenium deficiency	Metabolism and nutrition disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Scoliosis	Musculoskeletal and connective tissue disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Balance disorder	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Disturbance in attention	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Dizziness	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0002 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Dizziness postural	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Drooling	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Hyperreflexia	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Lethargy	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0013 events3 affected9 at risk EG0020 events0 affected9 at risk
Seizure	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0002 events1 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Somnolence	Nervous system disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Agitation	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Anxiety	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Bruxism	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Dermatillomania	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Insomnia	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0022 events2 affected9 at risk
Irritability	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Middle insomnia	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Nervousness	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Sleep disorder	Psychiatric disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Choking	Respiratory, thoracic and mediastinal disorders	MedDra 21.1	Systematic Assessment	EG0002 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Hyperventilation	Respiratory, thoracic and mediastinal disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected9 at risk EG0021 events1 affected9 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDra 21.1	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected9 at risk EG0020 events0 affected9 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk
Rash	Skin and subcutaneous tissue disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0011 events1 affected9 at risk EG0021 events1 affected9 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDra 21.1	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected9 at risk EG0020 events0 affected9 at risk

This study was terminated early due to enrollment challenges and the Coronavirus disease-2019 (COVID-19) pandemic. Numbers of participants in each treatment groups were small, which precluded the planned formal statistical inferences and limited data interpretation.

Certain Agreements

First MCP Posted Date

ID	Term
D015518	Rett Syndrome

Ancestor Terms

ID	Term
D038901	X-Linked Intellectual Disability
D008607	Intellectual Disability
D019954	Neurobehavioral Manifestations
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D040181	Genetic Diseases, X-Linked
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D020271	Heredodegenerative Disorders, Nervous System

ID	Term
D002185	Cannabidiol

Units	Counts
Participants	OG00010 OG0019 OG00210

Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID.

ID	Term
D002186	Cannabinoids
D013729	Terpenes
D006838	Hydrocarbons
D009930	Organic Chemicals