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

Jazz Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Epilepsy; Dravet Syndrome

Treatments: Drug: Placebo Control; Drug: GWP42003-P

Study type: Interventional

Funder types: Industry

Identifiers

NCT02224703

GWEP1424

2014-002939-34 (EudraCT Number)

Details and patient eligibility

About

To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.

Full description

This study was a 2:2:1:1 randomized, double-blind, 14-week comparison of two dose levels of GWP42003-P (10 milligram/kilogram [mg/kg]/day and 20 mg/kg/day) versus placebo (10 mg/kg/day dose-volume equivalent and 20 mg/kg/day dose-volume equivalent; presented as pooled placebo in the study). A 28-day screening period prior to randomization (to establish baseline parameters) preceded the treatment period, which consisted of a 2-week titration period followed by a 12-week maintenance period. The study aimed to determine the efficacy, safety, and tolerability of GWP42003-P compared with placebo. 20 mg/kg/day was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206). The first participant did not enroll into this study until the DSMC reviewed the safety data from Part A of study GWEP1332 (NCT02091206).

Following study completion, all participants were invited to continue to receive GWP42003-P in a separate open-label extension study (GWEP1415; NCT02224573).

Enrollment: 199 patients

Sex: All

Ages: 2 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Participant must have been male or female, aged between 2 and 18 years (inclusive).
• Participant must have had a documented history of Dravet syndrome that was not completely controlled by current antiepileptic drugs.
• Participant must have been taking 1 or more antiepileptic drugs at a dose that had been stable for at least 4 weeks.
• All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation) must have been stable for 4 weeks prior to screening and participant was willing to maintain a stable regimen throughout the study.

Key Exclusion Criteria:

• Participant had clinically significant unstable medical conditions other than epilepsy.
• Participant had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or randomization, other than epilepsy.
• Participant was currently using or had in the past used recreational cannabis, medicinal cannabis, or synthetic cannabinoid-based medications (including Sativex®) within the 3 months prior to study entry and was unwilling to abstain for the duration for the study.
• Participant had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
• There were plans for the participant to travel outside their country of residence during the study.
• Any history of suicidal behavior or any suicidal ideation of type four or five on the Columbia-Suicide Severity Rating Scale (Children's) at screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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199 participants in 3 patient groups, including a placebo group

10 mg/kg/day GWP42003-P

Experimental group

Description:

GWP42003-P oral solution (100 mg/milliliter \[mL\] cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.

Treatment:

Drug: GWP42003-P

20 mg/kg/day GWP42003-P

Experimental group

Description:

GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).

Treatment:

Drug: GWP42003-P

Placebo Control

Placebo Comparator group

Description:

Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.

Treatment:

Drug: Placebo Control