Trial Outcomes & Findings for Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1) (NCT NCT02091375)

NCT ID: NCT02091375

Last Updated: 2022-09-28

Results Overview

Convulsive seizures (atonic, clonic, tonic, or tonic-clonic) were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Percentage change from baseline was calculated as: (\[frequency during the treatment period - frequency during baseline\]/frequency during baseline) \* 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) \* 28. Baseline included all available data prior to Day 1 (28-day average). Negative percentages show an improvement from baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

120 participants

Primary outcome timeframe

Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)

Results posted on

2022-09-28

Participant Flow

Participant milestones

Participant milestones
Measure	GWP42003-P 20 mg/kg/Day Dose Participants received 20 milligrams (mg) per kilogram (kg) per day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the open-label extension (OLE) study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo Participants received placebo (0 mg/mL cannabidiol \[CBD\]), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Study STARTED	61	59
Overall Study Safety Analysis Set	61	59
Overall Study Intention to Treat (ITT) Analysis Set	61	59
Overall Study COMPLETED	52	56
Overall Study NOT COMPLETED	9	3

Reasons for withdrawal

Reasons for withdrawal
Measure	GWP42003-P 20 mg/kg/Day Dose Participants received 20 milligrams (mg) per kilogram (kg) per day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the open-label extension (OLE) study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo Participants received placebo (0 mg/mL cannabidiol \[CBD\]), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Study Adverse Event	8	1
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	0	1
Overall Study Withdrawn by the investigator	1	0

Baseline Characteristics

Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GWP42003-P 20 mg/kg/Day Dose n=61 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period. Participants received at least 1 dose of IMP; analyzed according to the actual treatment received (GWP42003-P).	Placebo n=59 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period. Participants received at least 1 dose of IMP; analyzed according to the actual treatment received (placebo).	Total n=120 Participants Total of all reporting groups
Age, Continuous	9.736 Years STANDARD_DEVIATION 4.7309 • n=5 Participants	9.779 Years STANDARD_DEVIATION 4.8505 • n=7 Participants	9.757 Years STANDARD_DEVIATION 4.7699 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	32 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	27 Participants n=7 Participants	62 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)

Population: ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=61 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Percentage Change From Baseline In Convulsive Seizure Frequency During The Treatment Period	-13.29 percent change Interval -52.53 to 20.2	-38.94 percent change Interval -69.53 to -4.83

SECONDARY outcome

Timeframe: Baseline to EOT (Day 99) or ET

Convulsive seizures (atonic, clonic, tonic, or tonic-clonic) were recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=61 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Number Of Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period	16 Participants	26 Participants

SECONDARY outcome

Timeframe: Baseline to EOT (Day 99) or ET

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=61 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Number of Participants With A ≥25%, ≥75% Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period ≥25% Reduction	26 Participants	38 Participants
Number of Participants With A ≥25%, ≥75% Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period ≥75% Reduction	7 Participants	14 Participants
Number of Participants With A ≥25%, ≥75% Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period 100% Reduction	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline to EOT (Day 99) or ET

Non-convulsive seizures (myoclonic, partial, or absence) were recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure. Only participants with non-convulsive seizures during the baseline period were included. Negative percentages show an improvement from baseline.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=37 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Percentage Change From Baseline In Non-Convulsive Seizure Frequency During The Treatment Period	-34.69 percent change Interval -97.5 to -0.7	-40.16 percent change Interval -92.1 to -3.6

SECONDARY outcome

Timeframe: Baseline to EOT (Day 99) or ET

Seizure duration was assessed qualitatively using the CGICSD. Caregivers were asked "Since the patient started treatment, please assess the average duration of the patient's seizures (comparing their condition now to their condition before treatment)"; responses included decrease, no change, or increase in average duration. For each seizure type, only participants with at least 1 seizure for the corresponding seizure type, reported at any time during the study, were included.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=61 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Tonic-Clonic Seizures · Decrease in average duration	8 Participants	17 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Tonic-Clonic Seizures · No change in average duration	31 Participants	32 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Tonic-Clonic Seizures · Increase in average duration	2 Participants	0 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Tonic Seizures · Decrease in average duration	2 Participants	4 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Tonic Seizures · No change in average duration	12 Participants	8 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Tonic Seizures · Increase in average duration	1 Participants	0 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Clonic Seizures · Decrease in average duration	3 Participants	5 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Clonic Seizures · No change in average duration	3 Participants	6 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Clonic Seizures · Increase in average duration	1 Participants	0 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Atonic Seizures · Decrease in average duration	2 Participants	2 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Atonic Seizures · No change in average duration	3 Participants	1 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Atonic Seizures · Increase in average duration	2 Participants	0 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Myoclonic Seizures · Decrease in average duration	3 Participants	4 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Myoclonic Seizures · No change in average duration	12 Participants	10 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Myoclonic Seizures · Increase in average duration	3 Participants	0 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Countable Partial Seizures · Decrease in average duration	2 Participants	5 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Countable Partial Seizures · No change in average duration	9 Participants	7 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Countable Partial Seizures · Increase in average duration	2 Participants	0 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Other Partial Seizures · Decrease in average duration	3 Participants	0 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Other Partial Seizures · No change in average duration	2 Participants	3 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Other Partial Seizures · Increase in average duration	0 Participants	0 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Absence Seizures · Decrease in average duration	6 Participants	4 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Absence Seizures · No change in average duration	12 Participants	11 Participants
Caregiver Global Impression Of Change In Seizure Duration (CGICSD) Absence Seizures · Increase in average duration	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline to EOT (Day 99) or ET

Population: Safety Analysis Set: included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.

The use of rescue medication was recorded by the participant or caregiver using a paper diary.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=61 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Number Of Participants Using Rescue Medication	41 Participants	36 Participants

SECONDARY outcome

Timeframe: Baseline to Safety Follow-up (Day 137)

Inpatient hospitalizations due to epilepsy were recorded by the participant or caregiver and through the serious adverse events (SAE) reporting process.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=61 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Number Of Participants With Inpatient Hospitalizations Due To Epilepsy Caregiver/participant-reported	1 participants	5 participants
Number Of Participants With Inpatient Hospitalizations Due To Epilepsy Investigator-reported (serious TEAE)	1 participants	2 participants

SECONDARY outcome

Timeframe: Baseline to Last Visit (Day 99) or ET

The sleep disruption 0 to 10 NRS questionnaire was completed by the participant's caregiver. The caregiver was asked 'On a scale of '0 to 10', please indicate the number that best describes your child's sleep disruption in the last week.' The markers ranged from 0 = 'slept extremely well' to 10 = 'unable to sleep at all'. The change from baseline in the sleep disruption 0 to 10 numerical rating scale score was analyzed using an analysis of covariance (ANCOVA) model with baseline and age group (2 to 5 years, 6 to 12 years and 13 to 18 years) as covariates and treatment group as a fixed factor. A negative change from baseline represents an improvement in sleep. Last visit for endpoints assessed at clinic visits was defined as the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=59 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Change From Baseline In Sleep Disruption 0 To 10 Numerical Rating Scale (0 to 10 NRS) Score	-0.3 units on a scale Interval -1.1 to 0.5	-0.7 units on a scale Interval -1.5 to 0.1

SECONDARY outcome

Timeframe: Baseline to Last Visit (Day 99) or ET

The ESS questionnaire was completed by the participant's caregiver. The change from baseline in the ESS score was analyzed using an ANCOVA model with baseline and age group (2 to 5 years, 6- to 2 years and 13 to 18 years) as covariates and treatment group as a fixed factor. The total score was the sum of the 8 item-scores and ranged from 0 to 24. A higher total score represents greater levels of daytime sleepiness.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=61 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Change From Baseline In Epworth Sleepiness Scale (ESS) Score	-0.69 units on a scale Interval -1.9 to 0.52	0.82 units on a scale Interval -0.36 to 1.99

SECONDARY outcome

Timeframe: Baseline to EOT (Day 99) or ET

The QOLCE questionnaire was completed by the parent or caregiver of participants aged 4 years and above. The change from baseline in the overall quality of life score was analyzed using an ANCOVA model with baseline and age group (2 to 5 years, 6 to 12 years and 13 to 18 years) as covariates and treatment group as a fixed factor. Zero represents the lowest or poorest category and 100 represents the highest level of functioning. The overall quality of life score was calculated by taking the mean of the subscale scores.

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=47 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Change From Baseline In Quality Of Life In Childhood Epilepsy (QOLCE) Score	4.1 units on a scale Interval 0.2 to 8.0	5.6 units on a scale Interval 1.9 to 9.3

SECONDARY outcome

Timeframe: Baseline to Last Visit (Day 99) or ET

The Vineland-II scores (standard scores and adaptive levels for each adaptive behavior domain, the adaptive behavior composite, and the maladaptive behavior index score and level) were assessed by the participant's caregiver. Scores were analyzed using an ANCOVA model with baseline and age group (2 to 5 years, 6 to 12 years, and 13 to 18 years) as covariates and treatment group as a fixed factor. Higher scores represent greater levels of functioning except for the maladaptive behavior index, for which a negative change from baseline represents an improvement in condition.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=61 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score Communication Domain Standard Score	3.0 units on a scale Interval 0.8 to 5.3	-0.8 units on a scale Interval -3.2 to 1.5
Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score Daily Living Skills Domain Standard Score	-0.8 units on a scale Interval -4.1 to 2.6	-0.8 units on a scale Interval -4.0 to 2.4
Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score Socialization Domain Standard Score	-0.6 units on a scale Interval -4.0 to 2.7	-0.6 units on a scale Interval -4.6 to 3.5
Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score Motor Skills Domain Standard Score	1.7 units on a scale Interval -1.1 to 4.5	-2.5 units on a scale Interval -5.5 to 0.5
Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score Adaptive Behavior Composite Standard Score	0.6 units on a scale Interval -2.1 to 3.3	-2.0 units on a scale Interval -5.2 to 1.1
Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score Maladaptive Behavior Index v-Scale Score	-0.4 units on a scale Interval -0.8 to 0.0	-0.3 units on a scale Interval -0.7 to 0.1

SECONDARY outcome

Timeframe: Baseline to Last Visit (Day 99) or ET

The CGIC was used to assess the participant's overall condition on a 7-point scale using the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse" (1 = very much improved; 7 = very much worse). On Day 1 (prior to starting IMP), 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.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.	GWP42003-P 20 mg/kg/Day Dose n=60 Participants Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Caregiver Global Impression Of Change (CGIC) Slightly Worse	6 Participants	3 Participants
Caregiver Global Impression Of Change (CGIC) Very Much Improved	4 Participants	9 Participants
Caregiver Global Impression Of Change (CGIC) Much Improved	4 Participants	10 Participants
Caregiver Global Impression Of Change (CGIC) Slightly Improved	12 Participants	18 Participants
Caregiver Global Impression Of Change (CGIC) No Change	31 Participants	15 Participants
Caregiver Global Impression Of Change (CGIC) Much Worse	1 Participants	4 Participants
Caregiver Global Impression Of Change (CGIC) Very Much Worse	0 Participants	1 Participants

Adverse Events

GWP42003-P 20 mg/kg/Day Dose

Serious events: 10 serious events

Other events: 46 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Enquires

GW Research Ltd.

Email: [email protected], [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	GWP42003-P 20 mg/kg/Day Dose n=61 participants at risk Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo n=59 participants at risk Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Gastrointestinal disorders Abdominal distension	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Gastrointestinal disorders Abdominal pain	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
General disorders Asthenia	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
General disorders Fatigue	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Infections and infestations Lower respiratory tract infection	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Infections and infestations Oral herpes	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Infections and infestations Pneumonia	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Investigations Aspartate aminotransferase increased	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Investigations Gamma-glutamyltransferase	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Investigations Liver function test abnormal	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Investigations Platelet count	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Investigations Weight decreased	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Metabolism and nutrition disorders Decreased appetite	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Metabolism and nutrition disorders Hypophagia	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Status epilepticus	4.9% 3/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	5.1% 3/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Convulsion	3.3% 2/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	1.7% 1/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Somnolence	4.9% 3/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Hypotonia	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Lethargy	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Myoclonus	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	1.7% 1/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Vascular disorders Hypovolaemic shock	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.

Measure	GWP42003-P 20 mg/kg/Day Dose n=61 participants at risk Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo n=59 participants at risk Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Gastrointestinal disorders Diarrhoea	31.1% 19/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	10.2% 6/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Gastrointestinal disorders Vomiting	14.8% 9/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	5.1% 3/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
General disorders Pyrexia	14.8% 9/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	8.5% 5/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
General disorders Fatigue	18.0% 11/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	3.4% 2/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Infections and infestations Upper respiratory tract infection	11.5% 7/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	8.5% 5/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Infections and infestations Nasopharyngitis	4.9% 3/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	5.1% 3/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Investigations Gamma-glutamyltransferase increased	6.6% 4/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Investigations Transaminases increased	6.6% 4/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Investigations Weight decreased	6.6% 4/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Metabolism and nutrition disorders Decreased appetite	26.2% 16/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	5.1% 3/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Somnolence	31.1% 19/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	10.2% 6/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Lethargy	11.5% 7/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	5.1% 3/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Headache	1.6% 1/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	5.1% 3/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Convulsion	8.2% 5/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	3.4% 2/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Psychiatric disorders Irritability	6.6% 4/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	0.00% 0/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Respiratory, thoracic and mediastinal disorders Cough	6.6% 4/61 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.	3.4% 2/59 • Day 1 (after dosing) to Day 137 Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.