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A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults (GWPCARE4)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd
ClinicalTrials.gov Identifier:
NCT02224690
First received: August 21, 2014
Last updated: October 4, 2016
Last verified: October 2016
  Purpose
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in subjects with Lennox-Gastaut syndrome.

Condition Intervention Phase
Epilepsy
Lennox-Gastaut Syndrome
Drug: GWP42003-P
Drug: Placebo Control
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults.

Resource links provided by NLM:


Further study details as provided by GW Research Ltd:

Primary Outcome Measures:
  • Percentage change from baseline in number of drop seizures (average per 28 days) during the treatment period. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: Yes ]
    The primary endpoint is the percentage change from baseline in number of drop seizures (average per 28 days) during the treatment period (Day 1 to the end of the evaluable period) in subjects taking GWP42003-P compared with placebo. Non-parametric analyses will be used for the primary endpoint should the assumption for parametric analyses (e.g. Normality) not be valid.


Secondary Outcome Measures:
  • Percentage change from baseline in number of drop seizures (average per 28 days). [ Time Frame: 0-14 weeks ] [ Designated as safety issue: Yes ]
  • Number of subjects considered treatment responders, defined as those with a ≥25%, ≥50%, ≥75%, or 100% reduction in drop seizures from baseline. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: No ]
  • Number of subjects experiencing a >25% worsening, −25 to +25% no change, 25-50% improvement, 50-75% improvement or >75% improvement in drop seizures from baseline. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: Yes ]
  • Percentage change from baseline in number of non-drop seizures (average per week). [ Time Frame: 0-14 weeks ] [ Designated as safety issue: Yes ]
  • Percentage change from baseline in the frequencies of sub-types of seizures (average per week). [ Time Frame: 0-14 weeks ] [ Designated as safety issue: Yes ]
  • Percent change from baseline in quality of life. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: No ]
  • Changes from baseline in the Caregiver Global Impression of Change (CGIC) score. [ Time Frame: End of week 14 of treatment ] [ Designated as safety issue: No ]
  • The incidence of adverse events as measure of subject safety. [ Time Frame: Day -28 to Day 137 ] [ Designated as safety issue: Yes ]
  • The number of age-appropriate subjects with a treatment-emergent flag using the Columbia-Suicide Severity Rating Scale (C-SSRS or C-SSRS Children's depending on age) during the course of the study. [ Time Frame: Day -28 to Day 137 ] [ Designated as safety issue: Yes ]

Enrollment: 171
Study Start Date: March 2015
Study Completion Date: June 2016
Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GWP42003-P
GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring).
Drug: GWP42003-P
GWP42003-P oral solution
Other Names:
  • Cannabidiol
  • CBD
Placebo Comparator: Placebo Control
Placebo oral solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Drug: Placebo Control
Placebo oral solution
Other Name: Placebo

Detailed Description:

This study is a 1:1 randomized, double-blind, 14-week comparison of GWP42003-P versus placebo. The treatment period will consist of a two-week titration period followed by a 12-week maintenance period. The study will aim to determine the efficacy, safety and tolerability of GWP42003-P compared with placebo. The dose will be as recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332. The first subject will not enroll into this study until the DSMC has reviewed the safety data from Part A of study GWEP1332.

Following study completion, all subjects will be invited to continue to receive GWP42003-P in an open label extension (OLE) study (under a separate protocol).

  Eligibility

Ages Eligible for Study:   2 Years to 55 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Subject must be male or female aged between two and 55 years (inclusive).
  • Subject must have a documented history of Lennox-Gastaut syndrome. This includes written documentation of having met electroencephalogram (EEG) diagnostic criteria during the patient's history and evidence of at least one type of generalized seizure, including drop seizures (atonic, tonic, tonic-clonic or myoclonic) for at least six months.
  • Subjects who have a history of slow (<2.5 Hz) spike-and-wave pattern in an EEG prior to the enrollment into the baseline period.
  • Subjects should be refractory; that is having documented failures on more than one antiepileptic drug (AED).
  • Subject must be taking one or more AEDs at a dose which has been stable for at least four weeks prior to screening.
  • All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation [VNS]) must have been stable for four weeks prior to screening and patient is willing to maintain a stable regimen throughout the study. The ketogenic diet and VNS treatments are not accounted as an AED.

Key Exclusion Criteria:

  • Etiology of subject's seizures is a progressive neurologic disease. Subjects with tuberous sclerosis will not be excluded from study participation, unless there is a progressive tumor.
  • Subject has had an anoxic episode requiring resuscitation within six months of screening.
  • Subject has clinically significant unstable medical conditions other than epilepsy.
  • Subject has had clinically relevant symptoms or a clinically significant illness in the four weeks prior to screening or randomization, other than epilepsy.
  • Subject is currently using or has in the past used recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex®) within the three months prior to study entry and is unwilling to abstain for the duration of the study.
  • Subject has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), such as sesame oil.
  • Subject has been part of a clinical trial involving another IMP in the previous six months.
  • Subject has significantly impaired hepatic function at screening (Visit 1) or randomization (Visit 2) (Alanine aminotransferase [ALT] >5 x upper limit of normal [ULN] or total bilirubin [TBL] >2 x ULN) OR the ALT or Aspartate aminotransferase (AST) >3 x ULN and (TBL >2 x ULN or international normalized ratio >1.5). This criterion can only be confirmed once the laboratory results are available; subjects randomized into the study who are later found not to meet this criterion should be withdrawn from the study.
  • Any history of suicidal behavior or any suicidal ideation of type four or five on the Columbia Suicide Severity Rating Scale in the last month or at screening.
  • Subject is taking more than four concurrent AEDs.
  • Subject has taken corticotropins in the six months prior to screening.
  • Subject is currently taking long-term systemic steroids (excluding inhaled medication for asthma treatment) or any other daily medication known to exacerbate epilepsy. An exception will be made of prophylactic medication, for example, idiopathic nephrotic syndrome or asthma.
  • Subject is taking felbamate, and they have been taking it for less than one year prior to screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02224690

Locations
United States, Illinois
GW Investigational Site
Chicago, Illinois, United States
Sponsors and Collaborators
GW Research Ltd
  More Information

Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT02224690     History of Changes
Other Study ID Numbers: GWEP1423  2014-002941-23 
Study First Received: August 21, 2014
Last Updated: October 4, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by GW Research Ltd:
Cannabidiol
CBD
Epidiolex
GWP42003-P

Additional relevant MeSH terms:
Syndrome
Seizures
Lennox Gastaut Syndrome
Disease
Pathologic Processes
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Genetic Diseases, Inborn
Pharmaceutical Solutions

ClinicalTrials.gov processed this record on December 07, 2016