A Randomized Controlled Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6)

Seizures Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P, CBD) as Add-on Therapy in Patients With Tuberous Sclerosis Complex Who Experience Inadequately-controlled Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02544763
• Other study ID #: GWEP1521 Blinded Phase
• Secondary ID: 2015-002154-12
• Status: Completed
• Phase: Phase 3
• Start date: April 6, 2016
• Est. completion date: February 26, 2019

Study information

• Verified date: September 2022
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial consists of 2 parts: a double-blinded phase and an open-label extension phase. The blinded phase only will be described in this record. Participants will receive 1 of 2 doses of GWP42003-P or matching placebo. The primary clinical hypothesis is that there will be a difference between GWP42003-P and placebo in their effect on seizure frequency.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: February 26, 2019
• Est. primary completion date: January 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 65 Years

Eligibility

Key Inclusion Criteria:

• Participant has a well-documented clinical history of epilepsy.
• Participant has a clinical diagnosis of Tuberous Sclerosis Complex (TSC) according to the criteria agreed by the 2012 International TSC Consensus Conference.
• All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must have been stable for 1 month prior to screening and the participant is willing to maintain a stable regimen throughout the trial.

Key Exclusion Criteria:

• Participant has a history of pseudo-seizures.
• Participant has clinically significant unstable medical conditions other than epilepsy.
• Participant has an illness in the 4 weeks prior to screening or randomization, other than epilepsy, which in the opinion of the investigator could affect seizure frequency.
• Participant has undergone general anesthetic in the 4 weeks prior to screening or randomization.
• Participant has undergone surgery for epilepsy in the 6 months prior to screening.
• Participant is being considered for epilepsy surgery or any procedure involving general anesthesia.
• Participant has been taking felbamate for less than 1 year prior to screening.
• Participant is taking an oral mTOR inhibitor.
• Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), such as sesame oil.
• Participant has any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the C-SSRS in the last month or at screening.
• Participant is currently using or has in the past used recreational or medicinal cannabis, or cannabinoid-based medications, within the 3 months prior to screening and is unwilling to abstain for the duration for the study.
• Participant has tumor growth which, in the opinion of the Investigator, could affect the primary endpoint.
• Participant has significantly impaired hepatic function at the screening or randomization visit
• Participant has received an IMP within the 12 weeks prior to the screening visit.

Related Conditions & MeSH terms

• Sclerosis
• Seizures
• Tuberous Sclerosis
• Tuberous Sclerosis Complex

Intervention

Drug:
• GWP42003-P
Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
• Placebo
Yellow oily solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Locations

Country	Name	City	State
Australia	Austin Health	Heidelberg
Australia	Royal Brisbane and Women's Hospital	Herston
Australia	The Royal Melbourne Hospital	Parkville
Australia	Sydney Children's Hospital	Randwick
Netherlands	Erasmus MC/Sophia Children's Hospital	Rotterdam
Netherlands	UMC Utrecht/ Wilhelmina, Kinderziekenhuis	Utrecht
Poland	Vitamed Galaj I Cichomski Spólka Jawna	Bydgoszcz
Poland	Centrum Medyczne Plejady	Kraków
Poland	Wojewódzki Szpital Specjalistyczny im S. K. Wyszynskiego SPZOZ	Lublin
Poland	Instytut "Pomnik - Centrum Zdrowia Dziecka"	Warsaw
Poland	Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego w Warszawie	Warsaw
Poland	Centrum Neuropsychiatrii "Neuromed"	Wroclaw
Spain	Centro Médico Teknon	Barcelona
Spain	Clinical Research Unit	Barcelona
Spain	Unitat d'Epilèpsia	Barcelona
Spain	Hospital Infantil Universitario Niño Jesús	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
United Kingdom	Cardiff and Vale University Local Health Board	Cardiff
United Kingdom	Children and Young Adults' Research Unit	Cardiff
United Kingdom	NIHR Clinical Research Facility	London
United Kingdom	St George's University Hospitals NHS Foundation Trust	London
United States	University of Colorado Denver	Aurora	Colorado
United States	Mid Atlantic Epilepsy & Sleep Centre	Bethesda	Maryland
United States	UAB Epilepsy Center	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Texas Scottish Rite Hospital for Children	Dallas	Texas
United States	Cook Children's Health Care System	Fort Worth	Texas
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	UCLA-Pediatric Neurology	Los Angeles	California
United States	WellSpan Paediatric Neurology	Manchester	Pennsylvania
United States	Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Pediatric Neurology	Miami	Florida
United States	NYU Comprehensive Epilepsy Center	New York	New York
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Minnesota Epilepsy Group, P.A	Saint Paul	Minnesota
United States	Paediatric Neurology	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in the Number of Tuberous Sclerosis Complex (TSC)-Associated Seizures During the Treatment Period (Maintenance and Titration)	TSC-associated seizures included: focal motor seizures without impairment of consciousness or awareness (Type 1 focal motor); focal seizures with impairment of consciousness or awareness (Type 2 focal); focal seizures evolving to bilateral generalized convulsive seizures (Type 3 focal); and tonic-clonic, tonic, clonic, or atonic seizures that are countable. Percent change from Baseline was calculated as the (post-Baseline value minus the Baseline value) divided by the Baseline value x 100.	Baseline; up to Week 16
Secondary	Number of Participants Considered Treatment Responders During the Treatment Period (Maintenance and Titration)	Treatment responders are defined as those participants with a = 50% reduction in TSC-associated seizure frequency. TSC-associated seizures included: focal motor seizures without impairment of consciousness or awareness (Type 1 focal motor); focal seizures with impairment of consciousness or awareness (Type 2 focal); focal seizures evolving to bilateral generalized convulsive seizures (Type 3 focal); and tonic-clonic, tonic, clonic, or atonic seizures that are countable. Participants who withdrew from the trial during the treatment period are considered non-responders.	Baseline; up to Week 16
Secondary	Change From Baseline in the Caregiver Global Impression of Change (CGIC) or Participant Global Impression of Change (PGIC) Score at the Participant's Last Visit	The combined caregiver and participant summary uses either the caregiver or participant version if only one version was completed, or the caregiver version if both caregiver and participant versions were completed. The CGIC comprised the following question, to be rated on a 7-point scale (1, Very Much Improved; 2, Much Improved; 3, Slightly Improved; 4, No Change; 5, Slightly Worse; 6, Much Worse; 7, Very Much Worse): "Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment)." The SGIC comprised the following question, to be rated on a 7-point scale (1, Very Much Improved; 2, Much Improved; 3, Slightly Improved; 4, No Change; 5, Slightly Worse; 6, Much Worse; 7, Very Much Worse): "Since you started treatment, please assess the status of your overall condition (comparing your condition now to your condition before treatment)."	Baseline; up to Week 16
Secondary	Percent Change From Baseline in Total Seizures During the Treatment Period (Maintenance and Titration)	Total seizures included all seizure types combined. Percent change from Baseline was calculated as the (post-Baseline value minus the Baseline value) divided by the Baseline value x 100.	Baseline; up to Week 16
Secondary	Number of Participants With Any Severe Treatment-emergent Adverse Event (TEAE)	A TEAE was defined as an AE with a start date on or after the first dose of IMP during the Blinded Phase up to and including the date of first dose of the Open-label Extension (OLE) Phase (OLE Day 1).	up to approximately Week 22