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

NCT ID: NCT02224703

Last Updated: 2022-09-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

199 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-13

Study Completion Date

2018-04-09

Brief Summary

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

Detailed Description

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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).

Conditions

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Epilepsy Dravet Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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10 mg/kg/day GWP42003-P

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.

Group Type EXPERIMENTAL

GWP42003-P

Intervention Type DRUG

20 mg/kg/day GWP42003-P

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).

Group Type EXPERIMENTAL

GWP42003-P

Intervention Type DRUG

Placebo Control

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.

Group Type PLACEBO_COMPARATOR

Placebo Control

Intervention Type DRUG

Interventions

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GWP42003-P

Intervention Type DRUG

Placebo Control

Intervention Type DRUG

Other Intervention Names

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Cannabidiol CBD Epidiolex Placebo

Eligibility Criteria

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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.

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.
Minimum Eligible Age

2 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jazz Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham, Alabama, United States

Site Status

Little Rock, Arkansas, United States

Site Status

Los Angeles, California, United States

Site Status

Sacramento, California, United States

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Hartford, Connecticut, United States

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Miami, Florida, United States

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Savannah, Georgia, United States

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Chicago, Illinois, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Saint Paul, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Lebanon, New Hampshire, United States

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Buffalo, New York, United States

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Chapel Hill, North Carolina, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Austin, Texas, United States

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Fort Worth, Texas, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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Heidelberg, , Australia

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Randwick, , Australia

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Ramat Gan, , Israel

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Heeze, , Netherlands

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Zwolle, , Netherlands

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Krakow, , Poland

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Lodz, , Poland

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Warsaw, , Poland

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

Site Status

Pamplona, , Spain

Site Status

Seville, , Spain

Site Status

Valencia, , Spain

Site Status

Countries

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United States Australia Israel Netherlands Poland Spain

References

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Madan Cohen J, Checketts D, Dunayevich E, Gunning B, Hyslop A, Madhavan D, Villanueva V, Zolnowska M, Zuberi SM. Time to onset of cannabidiol treatment effects in Dravet syndrome: Analysis from two randomized controlled trials. Epilepsia. 2021 Sep;62(9):2218-2227. doi: 10.1111/epi.16974. Epub 2021 Jul 15.

Reference Type DERIVED
PMID: 34265088 (View on PubMed)

Miller I, Scheffer IE, Gunning B, Sanchez-Carpintero R, Gil-Nagel A, Perry MS, Saneto RP, Checketts D, Dunayevich E, Knappertz V; GWPCARE2 Study Group. Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome: A Randomized Clinical Trial. JAMA Neurol. 2020 May 1;77(5):613-621. doi: 10.1001/jamaneurol.2020.0073.

Reference Type DERIVED
PMID: 32119035 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2014-002939-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GWEP1424

Identifier Type: -

Identifier Source: org_study_id

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