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Clinical Trial Results:
A double-blind, placebo-controlled two-part study to investigate the dose-ranging safety and pharmacokinetics, followed by the efficacy and safety of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.

Summary
EudraCT number	2014-000995-24
Trial protocol	GB PL
Global end of trial date	26 Nov 2015

Results information
Results version number	v1(current)
This version publication date	27 Sep 2018
First version publication date	27 Sep 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GWEP1332

ISRCTN number

US NCT number

NCT02091206

WHO universal trial number (UTN)

Other trial identifiers

NCT02091206: NCT number for GWEP1332A, NCT02091375: NCT Number for GWEP1332B

Sponsor organisation name

GW Research Ltd.

Sponsor organisation address

Sovereign House, Vision Park, Chivers Way, Histon, Cambridge, United Kingdom, CB24 9BZ

Public contact

Alternate contact: medinfo@greenwichbiosciences.com, GW Research Ltd., medinfo@gwpharm.com

Scientific contact

Alternate contact: medinfo@greenwichbiosciences.com, GW Research Ltd., medinfo@gwpharm.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001964-PIP01-16

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

26 Nov 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

26 Nov 2015

Global end of trial reached?

Yes

Global end of trial date

26 Nov 2015

Was the trial ended prematurely?

Main objective of the trial

Part A: To evaluate the safety of multiple doses of GWP42003-P compared with placebo with respect to: • Incidence, type and severity of adverse events (AEs). • Effect on vital signs, physical examination parameters including weight. • Effect on 12-lead electrocardiogram (ECG) findings. • Effect on laboratory parameters. • Changes in seizure frequency. Part B: • To assess the efficacy of GWP42003-P as an adjunctive antiepileptic treatment compared with placebo, with respect to the percentage change from baseline during the treatment period of the study in convulsive seizure frequency.

Protection of trial subjects

This study was conducted in accordance with International Council on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 Oct 2014

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

4 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 102

Country: Number of subjects enrolled

Poland: 14

Country: Number of subjects enrolled

United Kingdom: 20

Country: Number of subjects enrolled

France: 18

Worldwide total number of subjects

154

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

110

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

This multi-center study consisted of 2 parts: Part A was a randomized, double-blind 21-day treatment study period. Part B was a randomized, double-blind, placebo-controlled, 14-week treatment study period that enrolled an entirely new group of participants, and those who failed the entry criteria for Part A were eligible to take part in Part B.

Period 1 title

Parts A and B Combined (BL + treatment) (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Part A GWP42003-P 5 mg/kg/day Dose

Arm description

Participants received GWP42003-P 5 milligrams per kilogram per day (mg/kg/day) administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 5 mg/kg/day over 3 days and remained at this dose for the rest of the 21-day treatment period (19 days). The 21-day treatment period was followed by a 10-day taper (10% per day) period.

Arm type

Experimental

Investigational medicinal product name

GWP42003-P

Investigational medicinal product code

Other name

Cannibidiol, CBD, Epidiolex

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

GWP42003-P was presented an oral solution containing 25 or 100 mg/milliliter (mL) cannabidiol (CBD) dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Part A GWP42003-P 10 mg/kg/day Dose

Arm description

Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the rest of the 21-day treatment period (15 days). The 21-day treatment period was followed by a 10-day taper (10% per day) period.

Arm type

Experimental

Investigational medicinal product name

GWP42003-P

Investigational medicinal product code

Other name

Cannibidiol, CBD, Epidiolex

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

GWP42003-P was presented an oral solution containing 25 or 100 mg/mL CBD dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Part A GWP42003-P 20 mg/kg/day Dose

Arm description

Part A Participants received GWP42003-P 20 mg/kg/day 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 rest of the 21-day treatment period (11 days). The 21-day treatment period was followed by a 10-day taper (10% per day) period.

Arm type

Experimental

Investigational medicinal product name

GWP42003-P

Investigational medicinal product code

Other name

Cannibidiol, CBD, Epidiolex

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Part A Placebo

Arm description

Participants received placebo (0 mg/mL CBD), volume-matched to one of the 3 dose levels (5, 10, or 20 mg/kg/day), administered orally, half in the morning and half in the evening for 21 days. To maintain the blinded aspect of the study, participants titrated the placebo dose over 3 to 11 days according to the matched investigational medicinal product (IMP) group (3, 7, and 11 days for the 5, 10, or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the rest of the 21-day treatment period. The 21-day treatment period was followed by a 10-day taper (10% per day of the matched dose) period.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Participants received placebo (0 mg/mL CBD) dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Part B GWP42003-P 20 mg/kg/day Dose

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

GWP42003-P

Investigational medicinal product code

Other name

Cannibidiol, CBD, Epidiolex

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

GWP42003-P was presented an oral solution containing 100 mg/mL CBD dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Part B Placebo

Arm description

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.

Arm type

Placebo

Investigational medicinal product name

Part B Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Participants received placebo (0 mg/mL CBD) dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Number of subjects in period 1	Part A GWP42003-P 5 mg/kg/day Dose	Part A GWP42003-P 10 mg/kg/day Dose	Part A GWP42003-P 20 mg/kg/day Dose	Part A Placebo	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Started	10	8	9	7	61	59
Safety Analysis Set	10	8	9	7	61	59
Completed	10	7	8	7	52	56
Not completed	0	1	1	0	9	3
Withdrawn by investigator	-	-	-	-	1	-
Consent withdrawn by subject	-	-	-	-	-	1
Adverse event, non-fatal	-	1	-	-	8	1
Met withdrawal criteria	-	-	1	-	-	-
Lost to follow-up	-	-	-	-	-	1

Baseline characteristics

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Reporting group title

Part A GWP42003-P 5 mg/kg/day Dose

Reporting group description

Reporting group title

Part A GWP42003-P 10 mg/kg/day Dose

Reporting group description

Reporting group title

Part A GWP42003-P 20 mg/kg/day Dose

Reporting group description

Reporting group title

Part A Placebo

Reporting group description

Reporting group title

Part B GWP42003-P 20 mg/kg/day Dose

Reporting group description

Reporting group title

Part B Placebo

Reporting group description

Reporting group values	Part A GWP42003-P 5 mg/kg/day Dose	Part A GWP42003-P 10 mg/kg/day Dose	Part A GWP42003-P 20 mg/kg/day Dose	Part A Placebo	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo	Total
Number of subjects	10	8	9	7	61	59	154
Age categorical
Units: Subjects
Children (2-11 years)	10	8	9	7	38	38	110
Adolescents (12-17 years)	0	0	0	0	22	19	41
Adults (18-64 years)	0	0	0	0	1	2	3
Age continuous
Units: years
arithmetic mean (standard deviation)	7.150 ( 1.8955 )	7.368 ( 2.1229 )	8.671 ( 1.7957 )	6.978 ( 0.9476 )	9.736 ( 4.7309 )	9.779 ( 4.8505 )	-
Gender categorical
Units: Subjects
Female	5	5	6	2	26	32	76
Male	5	3	3	5	35	27	78

End points

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Reporting group title

Part A GWP42003-P 5 mg/kg/day Dose

Reporting group description

Reporting group title

Part A GWP42003-P 10 mg/kg/day Dose

Reporting group description

Reporting group title

Part A GWP42003-P 20 mg/kg/day Dose

Reporting group description

Reporting group title

Part A Placebo

Reporting group description

Reporting group title

Part B GWP42003-P 20 mg/kg/day Dose

Reporting group description

Reporting group title

Part B Placebo

Reporting group description

Primary: Part A: Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)

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End point title

Part A: Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs) ^[1] ^[2]

End point description

A TEAE was defined as an AE with an onset date on or after the first dose of investigational medicinal product (IMP). If an AE had a partial onset date and it was unclear from the partial date (or the stop date) whether the AE started prior to or following the first dose of IMP then the AE was considered a TEAE. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through the Safety Follow-up Visit (Day 60) is shown. A summary of serious and all other non-serious AEs regardless of causality is located in the Adverse Events module.

End point type

Primary

End point timeframe

Baseline (Day 1) through Safety follow-up visit (Day 60)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Quantitative statistical analyses were not performed on safety endpoints for Part A of the study.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part A of the study only. Severe TEAE data are not presented for Part B.

End point values	Part A GWP42003-P 5 mg/kg/day Dose	Part A GWP42003-P 10 mg/kg/day Dose	Part A GWP42003-P 20 mg/kg/day Dose	Part A Placebo
Number of subjects analysed	10	8	9	7
Units: Participants	2	1	0	1

No statistical analyses for this end point

Primary: Part B: Percentage Change From Baseline In Convulsive Seizure Frequency During The Treatment Period

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End point title

Part B: Percentage Change From Baseline In Convulsive Seizure Frequency During The Treatment Period ^[3]

End point description

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.

End point type

Primary

End point timeframe

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

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. Change in convulsive seizure frequency data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	61	59
Units: Percent change
median (inter-quartile range (Q1-Q3))	-38.94 (-69.53 to -4.83)	-13.29 (-52.53 to 20.20)

GWP42003-P 20 mg/kg/Day Dose, Placebo

Comparison groups

Part B GWP42003-P 20 mg/kg/day Dose v Part B Placebo

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0123 ^[4]

Method

Wilcoxon rank-sum test

Parameter type

Median difference (final values)

Point estimate

-22.79

Confidence interval

level

95%

sides

2-sided

lower limit

-41.06

upper limit

-5.43

Notes
[4] - The Wilcoxon test was used to calculate the p value, while the point estimate and confidence intervals were calculated using the Hodges–Lehmann approach.

Secondary: Part A: Area Under The Concentration-Time Curve Calculated To The Last Observable Concentration At Time T (AUC0-t) For CBD And Its Metabolites At Days 1 And 22

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End point title

Part A: Area Under The Concentration-Time Curve Calculated To The Last Observable Concentration At Time T (AUC0-t) For CBD And Its Metabolites At Days 1 And 22 ^[5]

End point description

AUC0-t for CBD and its major metabolites, 6-hydroxy-CBD (6-OH-CBD), 7-hydroxy-CBD (7-OH-CBD), and 7-carboxy-cannabidiol (7-COOH-CBD) were calculated using blood samples collected before and after IMP dosing on Days 1 and 22. One sample was collected predose, 2 to 3 hours postdose, and 4 to 6 hours postdose for CBD and its metabolites. Results are presented for participants who received GWP42003-P at 5, 10, or 20 mg/kg/day during the study and for participants with a numeric result for the given evaluation. Data presented are geometric means (geometric coefficient of variation [%]).

End point type

Secondary

End point timeframe

Predose and 2-6 hours postdose on Days 1 and 22

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part A of the study only. PK data are not presented for Part B.

End point values	Part A GWP42003-P 5 mg/kg/day Dose	Part A GWP42003-P 10 mg/kg/day Dose	Part A GWP42003-P 20 mg/kg/day Dose
Number of subjects analysed	10 ^[6]	8 ^[7]	9 ^[8]
Units: hours*nanograms/mL
geometric mean (geometric coefficient of variation)
Day 1 CBD	70.61 ( 20.38 )	66.35 ( 120.8 )	73.69 ( 96.64 )
Day 22 CBD	240.8 ( 100.8 )	721.8 ( 79.92 )	962.6 ( 93.43 )
Day 1 6-OH-CBD	3.27 ( 132 )	2.79 ( 87.7 )	5.16 ( 57.2 )
Day 22 6-OH-CBD	9.33 ( 119 )	26.3 ( 82.9 )	58.6 ( 90.1 )
Day 1 7-OH-CBD	21.9 ( 57.0 )	18.4 ( 299 )	30.2 ( 105 )
Day 22 7-OH-CBD	131 ( 107 )	244 ( 120 )	508 ( 96.0 )
Day 1 7-COOH-CBD	297 ( 97.3 )	125 ( 1750 )	195 ( 573 )
Day 22 7-COOH-CBD	4190 ( 81.20 )	9220 ( 178 )	15500 ( 148 )

Notes
[6] - CBD (Day 1) 5 (Day 22) 9 6-OH-CBD (1) 3 (22) 8 7-OH-CBD (1) 5 (22) 8 7-COOH-CBD (1) 6 (22) 9
[7] - CBD (Day 1) 7 (Day 22) 7 6-OH-CBD (1) 5 (22) 7 7-OH-CBD (1) 7 (22) 7 7-COOH-CBD (1) 6 (22) 5
[8] - CBD (Day 1) 7 (Day 22) 7 6-OH-CBD (1) 5 (22) 6 7-OH-CBD (1) 8 (22) 6 7-COOH-CBD (1) 6 (22) 5

No statistical analyses for this end point

Secondary: Part A: Mean Percentage Change From Baseline To End Of Treatment In Plasma Clobazam (CLB) And N-Desmethylclobazam (N-CLB) Concentrations

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End point title

Part A: Mean Percentage Change From Baseline To End Of Treatment In Plasma Clobazam (CLB) And N-Desmethylclobazam (N-CLB) Concentrations ^[9]

End point description

Plasma concentrations of CLB and N-CLB were measured on Days 1 and 22. Participants were instructed to take their daily dose of CLB 2 hours prior to the anticipated pre-IMP blood specimen collection on both days. Blood samples were collected prior to administration of IMP. Results are presented for a subgroup of participants who took CLB during the study and had PK samples analyzed at both pharmacokinetics (PK) sampling visits (Days 1 and 22).

End point type

Secondary

End point timeframe

Predose on Days 1 and 22

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part A of the study only. CLB and N-CLB data are not presented for Part B.

End point values	Part A GWP42003-P 5 mg/kg/day Dose	Part A GWP42003-P 10 mg/kg/day Dose	Part A GWP42003-P 20 mg/kg/day Dose	Part A Placebo
Number of subjects analysed	6	6	5	5
Units: percent change
number (not applicable)
% change in CLB	-1.2	18.0	29.6	15.1
% change in N-CLB	258.7	170.7	228.9	-5.6

No statistical analyses for this end point

Secondary: Part B: Number Of Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period

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End point title

Part B: Number Of Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period ^[10]

End point description

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.

End point type

Secondary

End point timeframe

Baseline to EOT (Day 99) or ET

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. Reduction in seizure frequency data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	61	59
Units: Participants
≥50% Reduction	26	16

GWP42003-P 20 mg/kg/Day Dose, Placebo

Comparison groups

Part B GWP42003-P 20 mg/kg/day Dose v Part B Placebo

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0784

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

4.3

Secondary: Part B: Number Of Participants with A ≥25%, ≥75%, Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period

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End point title

Part B: Number Of Participants with A ≥25%, ≥75%, Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period ^[11]

End point description

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

End point type

Secondary

End point timeframe

Baseline to EOT (Day 99) or ET

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. Convulsive seizure data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	61	59
Units: Participants
≥25% Reduction	38	26
≥75% Reduction	14	7
100% Reduction	3	0

No statistical analyses for this end point

Secondary: Part B: Percentage Change From Baseline In Non-Convulsive Seizure Frequency During The Treatment Period

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End point title

Part B: Percentage Change From Baseline In Non-Convulsive Seizure Frequency During The Treatment Period ^[12]

End point description

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.

End point type

Secondary

End point timeframe

Baseline to EOT (Day 99) or ET

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. Non-convulsive seizure frequency data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	37	41
Units: Percent change
median (inter-quartile range (Q1-Q3))	-40.16 (-92.1 to -3.6)	-34.69 (-97.5 to -0.7)

No statistical analyses for this end point

Secondary: Part B: Caregiver Global Impression Of Change In Seizure Duration (CGICSD)

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End point title

Part B: Caregiver Global Impression Of Change In Seizure Duration (CGICSD) ^[13]

End point description

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.

End point type

Secondary

End point timeframe

Baseline to EOT (Day 99) or ET

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. Duration of seizure subtype data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	61	59
Units: Participants
Tonic-Clonic Seizures Number Analyzed	49	41
Tonic-Clonic Seizures Decrease in average duration	17	8
Tonic-Clonic Seizures No change in aver. duration	32	31
Tonic-Clonic Seizures Increase in average duration	0	2
Tonic Seizures Number Analyzed	12	15
Tonic Seizures Decrease in average duration	4	2
Tonic Seizures No change in average duration	8	12
Tonic Seizures Increase in average duration	0	1
Clonic Seizures Number Analyzed	11	7
Clonic Seizures Decrease in average duration	5	3
Clonic Seizures No change in average duration	6	3
Clonic Seizures Increase in average duration	0	1
Atonic Seizures Number Analyzed	3	7
Atonic Seizures Decrease in average duration	2	2
Atonic Seizures No change in average duration	1	3
Atonic Seizures Increase in average duration	0	2
Myoclonic Seizures Number Analyzed	14	18
Myoclonic Seizures Decrease in average duration	4	3
Myoclonic Seizures No change in average duration	10	12
Myoclonic Seizures Increase in average duration	0	3
Countable Partial Seizures Number Analyzed	12	13
Countable Partial Seizures Decrease in aver. dur.	5	2
Countable Partial Seizures No change in aver. dur.	7	9
Countable Partial Seizures Increase in aver. dur.	0	2
Other Partial Seizures Number Analyzed	3	5
Other Partial Seizures Decrease in aver. dur.	0	3
Other Partial Seizures No change in aver. dur.	3	2
Other Partial Seizures Increase in aver. dur.	0	0
Absence Seizures Number Analyzed	16	19
Absence Seizures Decrease in average duration	4	6
Absence Seizures No change in average duration	11	12
Absence Seizures Increase in average duration	1	1

No statistical analyses for this end point

Secondary: Part B: Number Of Participants Using Rescue Medication

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End point title

Part B: Number Of Participants Using Rescue Medication ^[14]

End point description

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

End point type

Secondary

End point timeframe

Baseline to EOT (Day 99) or ET

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. Rescue medication data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	61	59
Units: Participants	36	41

No statistical analyses for this end point

Secondary: Part B: Number Of Participants With Inpatient Hospitalizations Due To Epilepsy

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End point title

Part B: Number Of Participants With Inpatient Hospitalizations Due To Epilepsy ^[15]

End point description

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

End point type

Secondary

End point timeframe

Baseline to Safety Follow-up (Day 137)

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part A of the study only. Hospitalization data are not presented for Part B.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	61	59
Units: Participants
Caregiver/participant-reported	5	1
Investigator-reported (serious TEAE)	2	1

No statistical analyses for this end point

Secondary: Part B: Change From Baseline In Sleep Disruption 0 To 10 Numerical Rating Scale (0 to 10 NRS) Score

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End point title

Part B: Change From Baseline In Sleep Disruption 0 To 10 Numerical Rating Scale (0 to 10 NRS) Score ^[16]

End point description

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.

End point type

Secondary

End point timeframe

Baseline to Last Visit (Day 99) or ET

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. Change In Sleep Disruption NRS data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	59	59
Units: units on a scale
least squares mean (confidence interval 95%)	-0.7 (-1.5 to 0.1)	-0.3 (-1.1 to 0.5)

No statistical analyses for this end point

Secondary: Part B: Change From Baseline In Epworth Sleepiness Scale (ESS) Score

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End point title

Part B: Change From Baseline In Epworth Sleepiness Scale (ESS) Score ^[17]

End point description

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.

End point type

Secondary

End point timeframe

Baseline to Last Visit (Day 99) or ET

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. ESS data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	61	58
Units: units on a scale
least squares mean (confidence interval 95%)	0.82 (-0.36 to 1.99)	-0.69 (-1.90 to 0.52)

No statistical analyses for this end point

Secondary: Part B: Change From Baseline In Quality Of Life In Childhood Epilepsy (QOLCE) Score

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End point title

Part B: Change From Baseline In Quality Of Life In Childhood Epilepsy (QOLCE) Score ^[18]

End point description

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.

End point type

Secondary

End point timeframe

Baseline to EOT (Day 99)

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Quantitative statistical analyses were not performed for this endpoint. Descriptive statistics are presented.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	47	44
Units: units on a scale
least squares mean (confidence interval 95%)	5.6 (1.9 to 9.3)	4.1 (0.2 to 8.0)

No statistical analyses for this end point

Secondary: Part B: Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score

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End point title

Part B: Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score ^[19]

End point description

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.

End point type

Secondary

End point timeframe

Baseline to Last Visit (Day 99) or ET

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. Vineland Adaptive Behavior Scale data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	61 ^[20]	59 ^[21]
Units: units on a scale
least squares mean (confidence interval 95%)
Communication Domain Standard Score	-0.8 (-3.2 to 1.5)	3.0 (0.8 to 5.3)
Daily Living Skills Domain Standard Score	-0.8 (-4.0 to 2.4)	-0.8 (-4.1 to 2.6)
Socialization Domain Standard Score	-0.6 (-4.6 to 3.5)	-0.6 (-4.0 to 2.7)
Motor Skills Domain Standard Score	-2.5 (-5.5 to 0.5)	1.7 (-1.1 to 4.5)
Adaptive Behavior Composite Standard Score	-2.0 (-5.2 to 1.1)	0.6 (-2.1 to 3.3)
Maladaptive Behavior Index v-Scale Score	-0.3 (-0.7 to 0.1)	-0.4 (-0.8 to 0.0)

Notes
[20] - Numbers Analysed CDSS 17 DLSDSS 20 SDSS 12 MSDSS 20 ABCSS 12 MBIvSS 47
[21] - Numbers Analysed CDSS 19 DLSDSS 19 SDSS 16 MSDSS 22 ABCSS 15 MBIvSS 48

No statistical analyses for this end point

Secondary: Part B: Caregiver Global Impression Of Change (CGIC)

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End point title

Part B: Caregiver Global Impression Of Change (CGIC) ^[22]

End point description

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.

End point type

Secondary

End point timeframe

Baseline to Last Visit (Day 99) or ET

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint provides data for Part B of the study only. CGIC data are not presented for Part A.

End point values	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Number of subjects analysed	60	58
Units: Participants
Very Much Improved	9	4
Much Improved	10	4
Slightly Improved	18	12
No Change	15	31
Slightly Worse	3	6
Much Worse	4	1
Very Much Worse	1	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline (Day 1) up to Day 60 (Part A) or Day 137 (Part B)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Part A GWP42003-P 5 mg/kg/day Dose

Reporting group description

Participants received GWP42003-P 5 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 5 mg/kg/day over 3 days and remained at this dose for the rest of the 21-day treatment period (19 days). The 21-day treatment period was followed by a 10-day taper (10% per day) period.

Reporting group title

Part A GWP42003-P 10 mg/kg/day Dose

Reporting group description

Reporting group title

Part A GWP42003-P 20 mg/kg/day Dose

Reporting group description

Reporting group title

Part A Placebo

Reporting group description

Participants received placebo (0 mg/mL CBD), volume matched to one of the 3 dose levels (5, 10, or 20 mg/kg/day), administered orally, half in the morning and half in the evening for 21 days. To maintain the blinded aspect of the study, participants titrated the placebo dose over 3 to 11 days according to the matched IMP group (3, 7, and 11 days for the 5, 10, or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the rest of the 21-day treatment period. The 21-day treatment period was followed by a 10-day taper (10% per day of the matched dose) period.

Reporting group title

Part B GWP42003-P 20 mg/kg/day Dose

Reporting group description

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 OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.

Reporting group title

Part B Placebo

Reporting group description

Serious adverse events	Part A GWP42003-P 5 mg/kg/day Dose	Part A GWP42003-P 10 mg/kg/day Dose	Part A GWP42003-P 20 mg/kg/day Dose	Part A Placebo	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 10 (10.00%)	2 / 8 (25.00%)	1 / 9 (11.11%)	1 / 7 (14.29%)	10 / 61 (16.39%)	3 / 59 (5.08%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gamma-glutamyltransferase
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver function test abnormal
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Platelet count
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Weight decreased
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypovolaemic shock
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	1 / 7 (14.29%)	2 / 61 (3.28%)	1 / 59 (1.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Status Epilepticus
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	3 / 61 (4.92%)	3 / 59 (5.08%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypotonia
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lethargy
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myoclonus
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Somnolence
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	3 / 61 (4.92%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 10 (0.00%)	2 / 8 (25.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthenia
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	1 / 59 (1.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash Maculo-papular
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Parvovirus Infection
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral Infection
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral herpes
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypophagia
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part A GWP42003-P 5 mg/kg/day Dose	Part A GWP42003-P 10 mg/kg/day Dose	Part A GWP42003-P 20 mg/kg/day Dose	Part A Placebo	Part B GWP42003-P 20 mg/kg/day Dose	Part B Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	8 / 10 (80.00%)	5 / 8 (62.50%)	7 / 9 (77.78%)	6 / 7 (85.71%)	46 / 61 (75.41%)	28 / 59 (47.46%)
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences all number	0	0	1	0	1	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences all number	0	0	0	1	1	0
Hepatic enzyme increased
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0
Liver function test abnormal
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	1 / 61 (1.64%)	1 / 59 (1.69%)
occurrences all number	0	0	1	0	1	1
Urine ketone body absent
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0
Urine ketone body present
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	4 / 61 (6.56%)	0 / 59 (0.00%)
occurrences all number	0	0	0	0	4	0
Transaminases increased
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	4 / 61 (6.56%)	0 / 59 (0.00%)
occurrences all number	0	0	0	0	4	0
Weight decreased
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	4 / 61 (6.56%)	0 / 59 (0.00%)
occurrences all number	0	0	0	0	4	0
Injury, poisoning and procedural complications
Accident
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0
Nervous system disorders
Ataxia
subjects affected / exposed	2 / 10 (20.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	2 / 61 (3.28%)	0 / 59 (0.00%)
occurrences all number	2	0	1	0	2	0
Convulsion
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	5 / 61 (8.20%)	2 / 59 (3.39%)
occurrences all number	0	0	0	1	5	3
Coordination abnormal
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 7 (0.00%)	2 / 61 (3.28%)	0 / 59 (0.00%)
occurrences all number	0	1	0	0	2	0
Dysarthria
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	1	0
Headache
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	1 / 61 (1.64%)	3 / 59 (5.08%)
occurrences all number	0	0	2	0	1	5
Poor quality sleep
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0
Psychomotor hyperactivity
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	2 / 61 (3.28%)	2 / 59 (3.39%)
occurrences all number	1	0	0	1	2	2
Sedation
subjects affected / exposed	2 / 10 (20.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)	0 / 7 (0.00%)	2 / 61 (3.28%)	0 / 59 (0.00%)
occurrences all number	2	0	2	0	2	0
Somnolence
subjects affected / exposed	2 / 10 (20.00%)	3 / 8 (37.50%)	0 / 9 (0.00%)	1 / 7 (14.29%)	19 / 61 (31.15%)	6 / 59 (10.17%)
occurrences all number	2	3	0	1	23	13
Tremor
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	2 / 61 (3.28%)	0 / 59 (0.00%)
occurrences all number	0	0	1	0	2	0
Lethargy
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	7 / 61 (11.48%)	3 / 59 (5.08%)
occurrences all number	0	0	0	0	9	4
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	2 / 7 (28.57%)	11 / 61 (18.03%)	2 / 59 (3.39%)
occurrences all number	0	0	1	2	12	2
Gait disturbance
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 7 (0.00%)	3 / 61 (4.92%)	0 / 59 (0.00%)
occurrences all number	0	1	0	0	3	0
Influenza like illness
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	0	1	0	0
Pyrexia
subjects affected / exposed	3 / 10 (30.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 7 (0.00%)	9 / 61 (14.75%)	5 / 59 (8.47%)
occurrences all number	3	1	0	0	13	7
Eye disorders
Diplopia
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	1	0	0	0
Gastrointestinal disorders
Abdominal Pain Upper
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	2	0	0	0
Constipation
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	1 / 61 (1.64%)	2 / 59 (3.39%)
occurrences all number	1	0	0	0	1	2
Diarrhoea
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	19 / 61 (31.15%)	6 / 59 (10.17%)
occurrences all number	0	0	0	1	33	8
Dry Mouth
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	2	0	0	0
Eructation
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	1	0	0	0
Haematochezia
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	2	0	0	0
Vomiting
subjects affected / exposed	1 / 10 (10.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)	0 / 7 (0.00%)	9 / 61 (14.75%)	3 / 59 (5.08%)
occurrences all number	1	1	2	0	13	5
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	4 / 61 (6.56%)	2 / 59 (3.39%)
occurrences all number	0	0	0	1	4	3
Skin and subcutaneous tissue disorders
Dermatitis diaper
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	0	1	0	0
Erythema
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0
Rash
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)	0 / 7 (0.00%)	2 / 61 (3.28%)	1 / 59 (1.69%)
occurrences all number	0	1	1	0	3	1
Rash papular
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	0 / 61 (0.00%)	1 / 59 (1.69%)
occurrences all number	0	0	1	0	0	1
Urticaria
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	1	0	0	0	0
Psychiatric disorders
Abnormal behaviour
subjects affected / exposed	3 / 10 (30.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	2 / 61 (3.28%)	1 / 59 (1.69%)
occurrences all number	3	0	0	0	2	1
Irritability
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 7 (0.00%)	4 / 61 (6.56%)	0 / 59 (0.00%)
occurrences all number	0	1	0	0	6	0
Mood swings
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	1 / 61 (1.64%)	0 / 59 (0.00%)
occurrences all number	0	0	0	1	1	0
Renal and urinary disorders
Proteinuria
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0
Infections and infestations
Erythema infectiosum
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	1	0	0	0
Gastroenteritis
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	2 / 7 (28.57%)	2 / 61 (3.28%)	0 / 59 (0.00%)
occurrences all number	1	0	0	2	2	0
Gastroenteritis viral
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	1 / 7 (14.29%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	1	1	0	0
Lower respiratory tract infection
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)	1 / 7 (14.29%)	3 / 61 (4.92%)	3 / 59 (5.08%)
occurrences all number	0	1	1	1	3	3
Otitis media acute
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	1	0	0	0
Pharyngitis streptococcal
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 7 (14.29%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	1	0	0
Pneumonia
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)	0 / 7 (0.00%)	1 / 61 (1.64%)	1 / 59 (1.69%)
occurrences all number	0	1	2	0	1	1
Upper respiratory tract infection
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	7 / 61 (11.48%)	5 / 59 (8.47%)
occurrences all number	1	0	0	0	7	6
Viral infection
subjects affected / exposed	0 / 10 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 7 (0.00%)	0 / 61 (0.00%)	2 / 59 (3.39%)
occurrences all number	0	0	1	0	0	2
Viral rash
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	4 / 9 (44.44%)	0 / 7 (0.00%)	16 / 61 (26.23%)	3 / 59 (5.08%)
occurrences all number	0	1	4	0	21	3
Increased appetite
subjects affected / exposed	0 / 10 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 7 (0.00%)	3 / 61 (4.92%)	0 / 59 (0.00%)
occurrences all number	0	1	0	0	3	0
Ketosis
subjects affected / exposed	1 / 10 (10.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 7 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)
occurrences all number	1	0	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

04 Nov 2014

Clarification of trial procedures, including the following -Added CGICSD as a secondary assessment and analysis of major metabolites of CBD. -Added a pre-randomization pregnancy test. -Clarified exclusion criteria related to previous use of cannabinoids. -Clarified study procedures, including collection of seizure information for Part A, IMP usage, rescue medication, concomitant anti-epilepsy drugs, and AEs for parts A and B; collection of epilepsy-specific genetic testing and prior anti-epileptic drugs; capturing seizure information and IMP supply; timing of CLB administration -Clarified baseline and safety follow-up periods and visit windows as well as time periods for safety calls and completing case report forms and collection of epilepsy-related hospitalization information -Clarified seizure types and subtypes -Clarified that any AE or drug-induced liver injury could be reason for withdrawal -Clarified when diary information would be collected -Clarified when the taper period would start for participants who terminated early -Added use of diagnostic review and clarified the qualifications for administering the C-SSRS -Clarified when seizures were considered AEs and when AEs should be reviewed by the DSMC

29 May 2015

Clarification of trial procedures, including the following: -Revision of endpoint analyses, including Part B primary and secondary endpoints to use the full treatment period (which included titration and maintenance periods); definition of "baseline" for statistical analyses; seizure frequency used in the sensitivity analysis for Part B, new sensitivity analyses for Part B; and details on multiple imputation methods for sensitivity analyses for the primary endpoint in Part B. -Revision/clarification of procedures, including Tanner staging age; monitoring of potential cases of DILI, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase levels until normalized; monitoring of the plasma concentration of concomitant anti-epilepsy drugs and dosage modification if concentrations are altered following administration of IMP; instructions for follow-up for elevated liver enzymes that were not considered DILI; clarification regarding who may participate in the C-SSRS; and collection of seizure count information for Part B. -Clarified assessments including effects of IMP on menstruation cycles and measuring plasma concentrations of anti-epilepsy drugs. -Clarification that only convulsive seizures in the first 28 days of the baseline period would count toward eligibility.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

In Part A, there were analytical issues for 7-OH-CBD related to reference material batch used during analysis. Data are qualitative.

http://www.ncbi.nlm.nih.gov/pubmed/29540584
http://www.ncbi.nlm.nih.gov/pubmed/28538134

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Clinical trials

Clinical Trial Results: A double-blind, placebo-controlled two-part study to investigate the dose-ranging safety and pharmacokinetics, followed by the efficacy and safety of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part A: Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)

Primary: Part A: Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)

Primary: Part B: Percentage Change From Baseline In Convulsive Seizure Frequency During The Treatment Period

Primary: Part B: Percentage Change From Baseline In Convulsive Seizure Frequency During The Treatment Period

Secondary: Part A: Area Under The Concentration-Time Curve Calculated To The Last Observable Concentration At Time T (AUC0-t) For CBD And Its Metabolites At Days 1 And 22

Secondary: Part A: Area Under The Concentration-Time Curve Calculated To The Last Observable Concentration At Time T (AUC0-t) For CBD And Its Metabolites At Days 1 And 22

Secondary: Part A: Mean Percentage Change From Baseline To End Of Treatment In Plasma Clobazam (CLB) And N-Desmethylclobazam (N-CLB) Concentrations

Secondary: Part A: Mean Percentage Change From Baseline To End Of Treatment In Plasma Clobazam (CLB) And N-Desmethylclobazam (N-CLB) Concentrations

Secondary: Part B: Number Of Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period

Secondary: Part B: Number Of Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period

Secondary: Part B: Number Of Participants with A ≥25%, ≥75%, Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period

Secondary: Part B: Number Of Participants with A ≥25%, ≥75%, Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period

Secondary: Part B: Percentage Change From Baseline In Non-Convulsive Seizure Frequency During The Treatment Period

Secondary: Part B: Percentage Change From Baseline In Non-Convulsive Seizure Frequency During The Treatment Period

Secondary: Part B: Caregiver Global Impression Of Change In Seizure Duration (CGICSD)

Secondary: Part B: Caregiver Global Impression Of Change In Seizure Duration (CGICSD)

Secondary: Part B: Number Of Participants Using Rescue Medication

Secondary: Part B: Number Of Participants Using Rescue Medication

Secondary: Part B: Number Of Participants With Inpatient Hospitalizations Due To Epilepsy

Secondary: Part B: Number Of Participants With Inpatient Hospitalizations Due To Epilepsy

Secondary: Part B: Change From Baseline In Sleep Disruption 0 To 10 Numerical Rating Scale (0 to 10 NRS) Score

Secondary: Part B: Change From Baseline In Sleep Disruption 0 To 10 Numerical Rating Scale (0 to 10 NRS) Score

Secondary: Part B: Change From Baseline In Epworth Sleepiness Scale (ESS) Score

Secondary: Part B: Change From Baseline In Epworth Sleepiness Scale (ESS) Score

Secondary: Part B: Change From Baseline In Quality Of Life In Childhood Epilepsy (QOLCE) Score

Secondary: Part B: Change From Baseline In Quality Of Life In Childhood Epilepsy (QOLCE) Score

Secondary: Part B: Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score

Secondary: Part B: Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score

Secondary: Part B: Caregiver Global Impression Of Change (CGIC)

Secondary: Part B: Caregiver Global Impression Of Change (CGIC)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
A double-blind, placebo-controlled two-part study to investigate the dose-ranging safety and pharmacokinetics, followed by the efficacy and safety of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.