Clinical trial NCT02091375: Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Dravet Syndrome
Keywords: Cannabidiol
CBD
Epidiolex
GWP42003-P
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-03-19
Enrollment: 120
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: GWEP1332 Part B recruited an entirely new group of participants than GWEP1332 Part A. Participants who failed the entry criteria for Part A were eligible to take part in Part B.

Part B was a 1:1 randomized, double-blind, placebo-controlled, 14-week comparison of GWP42003-P versus placebo. The aim of Part B was to assess the antiepileptic 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 in children and young adults.

Following the establishment of initial eligibility and baseline measurements, participants entered Part B and began a 28-day baseline observation period.

Eligible participants were then randomized to receive either GWP42003-P or placebo on a 1:1 basis and titrated up to the target dose that was identified in Part A (up to 20 milligrams \[mg\] per kilogram \[kg\] per day), which was confirmed following completion of Part A by an independent Data Safety Monitoring Committee who reviewed unblinded safety and pharmacokinetic data from Part A.

Participants received investigational medicinal product for 14 weeks, consisting of a titration period followed by a 12-week maintenance period.

Efficacy and safety were monitored at various clinic visits and via telephone. After 14 weeks of treatment, all participants were offered the option of entering an open label extension (OLE) study. Entry was within seven days of the final treatment visit. Participants who did not immediately enter the OLE study commenced a down-titration taper period lasting up to 10 days. The taper period was interrupted if the participant wished to enter the open label extension study within the seven-day timeframe.

For participants who opted not to enter the OLE study, a follow-up telephone call was made 28 days after the end of dosing and weekly safety telephone calls were made during the 28-day follow-up period.

Eligibility criteria: Key Inclusion Criteria:

* Participants were male or female aged between 2 and 18 years (inclusive).
* Participants had a documented history of Dravet Syndrome that was not completely controlled by current antiepileptic drugs.
* Participants took one or more antiepileptic drugs at a dose that had been stable for at least four weeks.
* All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation) were stable for four weeks prior to screening and participants were willing to maintain a stable regimen throughout the study.

Key Exclusion Criteria:

* Participants had clinically significant unstable medical conditions other than epilepsy.
* Participants had clinically relevant symptoms or a clinically significant illness in the four weeks prior to screening or randomization, other than epilepsy.
* Participants were currently using or had in the past used recreational or medicinal cannabis or synthetic cannabinoid based medications (including Sativex®) within the three months prior to study entry and were unwilling to abstain for the duration for the study.
* Participants had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
* Participants had been part of a previous clinical trial involving another investigational product in the previous six months.
* There were plans for the participants to travel outside their country of residence during the study.
* Participants previously randomized into this study. In particular, participants who participated in Part A of the study could not enter Part B.

Primary outcomes:
measure: Percentage Change From Baseline In Convulsive Seizure Frequency During The Treatment Period
timeFrame: Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)
Secondary outcomes:
measure: Number Of Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
timeFrame: Baseline to EOT (Day 99) or ET
measure: Number of Participants With A ≥25%, ≥75% Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
timeFrame: Baseline to EOT (Day 99) or ET
measure: Percentage Change From Baseline In Non-Convulsive Seizure Frequency During The Treatment Period
timeFrame: Baseline to EOT (Day 99) or ET
measure: Caregiver Global Impression Of Change In Seizure Duration (CGICSD)
timeFrame: Baseline to EOT (Day 99) or ET
measure: Number Of Participants Using Rescue Medication
timeFrame: Baseline to EOT (Day 99) or ET
measure: Number Of Participants With Inpatient Hospitalizations Due To Epilepsy
timeFrame: Baseline to Safety Follow-up (Day 137)
measure: Change From Baseline In Sleep Disruption 0 To 10 Numerical Rating Scale (0 to 10 NRS) Score
timeFrame: Baseline to Last Visit (Day 99) or ET
measure: Change From Baseline In Epworth Sleepiness Scale (ESS) Score
timeFrame: Baseline to Last Visit (Day 99) or ET
measure: Change From Baseline In Quality Of Life In Childhood Epilepsy (QOLCE) Score
timeFrame: Baseline to EOT (Day 99) or ET
measure: Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score
timeFrame: Baseline to Last Visit (Day 99) or ET
measure: Caregiver Global Impression Of Change (CGIC)
timeFrame: Baseline to Last Visit (Day 99) or ET
Other outcomes:
Locations:
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Boston
country: United States
state: Massachusetts
city: Rochester
country: United States
state: Minnesota
city: New York
country: United States
state: New York
city: Winston-Salem
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Marseille
country: France
city: Paris
country: France
city: Strasbourg
country: France
city: Toulouse
country: France
city: Gdańsk
country: Poland
city: Kraków
country: Poland
city: Glasgow
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
Study officials:
References:
citation: Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S; Cannabidiol in Dravet Syndrome Study Group. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-2020. doi: 10.1056/NEJMoa1611618.
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.