Clinical trial NCT02224703: GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
Official title: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Dravet Syndrome
Keywords: Cannabidiol
CBD
GWP42003-P
Epidiolex
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-08-25
Enrollment: 199
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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).

Eligibility 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.

Primary outcomes:
measure: Change In Convulsive Seizures During The Treatment Period Compared To Baseline
timeFrame: Baseline to Day 99 or Early Termination (ET)
Secondary outcomes:
measure: Change In Total Seizures During The Treatment Period Compared To Baseline
timeFrame: Baseline to Day 99 or ET
measure: Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
timeFrame: Baseline to Day 99 or ET
measure: Caregiver Global Impression Of Change (CGIC) At The Last Visit
timeFrame: Baseline to Last Visit
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Hartford
country: United States
state: Connecticut
city: Miami
country: United States
state: Florida
city: Savannah
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Saint Paul
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Lebanon
country: United States
state: New Hampshire
city: Buffalo
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Heidelberg
country: Australia
city: Randwick
country: Australia
city: Ramat Gan
country: Israel
city: Heeze
country: Netherlands
city: Zwolle
country: Netherlands
city: Kraków
country: Poland
city: Warszawa
country: Poland
city: Łódź
country: Poland
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Pamplona
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
Study officials:
References:
citation: 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.
citation: 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.