An Open-label Extension Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6)

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

This trial consists of 2 parts: a double-blinded phase and an open-label extension phase. The open-label extension phase only will be described in this record. All participants will receive the same dose of GWP42003-P. However, investigators may subsequently decrease or increase the participant's dose until the optimal dose is found.

Study Overview

• Status: Completed
• Conditions: Seizures; Tuberous Sclerosis Complex
• Intervention / Treatment: Drug: GWP42003-P

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Completion of the GWEP1521 Blinded Phase

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GWP42003-P; 100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening). Participants will be dosed up to a maximum of 50 mg/kg/day. Dose may be lower if Investigator judges benefit and/or tolerability issues.	Drug: GWP42003-P; Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.; Other Names: Cannabidiol; CBD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Treatment-emergent Adverse Events, Discontinuations Due to AEs, Serious AEs, and Treatment-related AEs (TEAE)	An adverse event (AE) was defined as any new unfavorable/unintended signs/symptoms (including abnormal laboratory findings), or diagnosis or worsening of a pre-existing condition, which occurred following screening and at any point up to the post-treatment safety follow-up visit, which may or may not be related to the IMP. An AE that started, or worsened in severity or seriousness, following the first dose of IMP was considered a TEAE. A serious AE was defined as any AE that results in any of the following outcomes: death, life-threatening adverse experience, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or cancer, any other experience that suggests a significant hazard, contraindication, side effect or precaution that may require medical or surgical intervention to prevent one of the outcomes listed above, or an event that changes the risk/benefit ratio of the study.	OLE Day 1 up to 4 years
Number of Participants With Any TEAE, by Severity	An adverse event (AE) was defined as any new unfavorable/unintended signs/symptoms (including abnormal laboratory findings), or diagnosis or worsening of a pre-existing condition, which occurred following screening and at any point up to the post-treatment safety follow-up visit, which may or may not be related to the IMP. An AE that started, or worsened in severity or seriousness, following the first dose of IMP was considered a TEAE. Grade 1 (Mild) is defined as asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate) is defined as minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living (ADL). Grade 3 (Severe) is defined as medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.	OLE Day 1 up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in the Number of TSC-associated Seizures During the OLE Treatment Period	TSC-associated seizures include: focal motor seizures without impairment of consciousness or awareness; focal seizures with impairment of consciousness or awareness; focal seizures evolving to bilateral generalized convulsive seizures and tonic-clonic, tonic, clonic or atonic seizures. A negative percent change from baseline indicates improvement.	OLE Day 1 up to 4 years
Number of Participants Considered Treatment Responders During the OLE Treatment Period	Treatment responders were defined as those participants with a ≥50% reduction from baseline in TSC-associated seizure frequency, during the treatment period, for participants who had not withdrawn from the trial during the treatment period. 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 were countable. Participants who withdrew from the trial during the treatment period were considered non-responders.	OLE Day 1 up to 4 years
Caregiver Global Impression of Change (CGIC) and Subject Global Impression of Change (SGIC) Score During the OLE Treatment Period	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)." The average CGIC and SGIC scores are being reported, with higher values indicating worse condition.	OLE Day 1 and up to 4 years
Percent Change From Baseline in Total Seizure Frequency During the OLE Treatment Period	Total seizures included all seizure types, eg. combination of TSC-associated and other seizures. 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 were countable. A negative percent change from baseline indicates improvement in total seizure frequency.	OLE Day 1 up to 4 years

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: GW Pharmaceuticals

Publications and helpful links

General Publications

• Thiele EA, Bebin EM, Bhathal H, Jansen FE, Kotulska K, Lawson JA, O'Callaghan FJ, Wong M, Sahebkar F, Checketts D, Knappertz V; GWPCARE6 Study Group. Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial. JAMA Neurol. 2021 Mar 1;78(3):285-292. doi: 10.1001/jamaneurol.2020.4607.
• Thiele EA, Bebin EM, Filloux F, Kwan P, Loftus R, Sahebkar F, Sparagana S, Wheless J. Long-term cannabidiol treatment for seizures in patients with tuberous sclerosis complex: An open-label extension trial. Epilepsia. 2022 Feb;63(2):426-439. doi: 10.1111/epi.17150. Epub 2021 Dec 27.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2016
• Primary Completion (Actual): June 11, 2021
• Study Completion (Actual): June 11, 2021

Study Registration Dates

• First Submitted: September 7, 2015
• First Submitted That Met QC Criteria: September 7, 2015
• First Posted (Estimate): September 9, 2015

Study Record Updates

• Last Update Posted (Actual): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms; Neurologic Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Hamartoma; Neoplasms, Multiple Primary; Sclerosis; Seizures; Tuberous Sclerosis; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: GWEP1521 Open-Label Extension; 2015-002154-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No