Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution

A Long-term Safety Study to Assess the Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution

This study will monitor for potential chronic liver injury and liver fibrosis, in participants treated with cannabidiol oral solution.

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberous Sclerosis Complex; Dravet Syndrome; Lennox Gastaut Syndrome
• Intervention / Treatment: Drug: Cannabidiol

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72758
      • Clinical Trial Site
  • California
    • Downey, California, United States, 90242
      • Clinical Trial Site
    • Long Beach, California, United States, 90806
      • Clinical Trial Site
    • Sacramento, California, United States, 95817
      • Clinical Trial Site
  • Florida
    • Miami, Florida, United States, 33136
      • Clinical Trial Site
    • Miami, Florida, United States, 33176
      • Clinical Trial Site
    • Orlando, Florida, United States, 32806
      • Clinical Trial Site
    • Tampa, Florida, United States, 33606
      • Clinical Trial Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Clinical Trial Site
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Clinical Trial Site
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Clinical Trial Site
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Clinical Trial Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Clinical Trial Site
  • New York
    • New York, New York, United States, 10016
      • Clinical Trial Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Clinical Trial Site
    • Durham, North Carolina, United States, 27708
      • Clinical Trial Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Clinical Trial Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Clinical Trial Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Clinical Trial Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Clinical Trial Site
  • Texas
    • Austin, Texas, United States, 78758
      • Clinical Trial Site
    • Dallas, Texas, United States, 75251
      • Clinical Trial Site
    • Houston, Texas, United States, 77030
      • Clinical Trial Site
    • Round Rock, Texas, United States, 78681
      • Clinical Trial Site
  • Virginia
    • Winchester, Virginia, United States, 22601
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant is within the approved age range as per labeling recommendations. Participants aged 1 to 3 years who are in the FibroScan subset will not undergo FibroScan assessments until they reach 4 years of age.
• Participant is either on existing Epidiolex therapy for treatment of a seizure disorder or is to be started on Epidiolex for treatment of an Food and Drug Administration (FDA)-approved indication.
• Participant is willing to refrain from strenuous exercise 48 to 72 hours prior to all study visits with the exception of unscheduled visits.
• Any non-pharmacological therapies (e.g., ketogenic diet) must also be stable up to 4 weeks prior to Screening Visit and expected to be stable throughout the duration of the study.

Exclusion Criteria:

• Participant is currently using or within 3 months of screening has used recreational or medicinal cannabis, or synthetic cannabinoid-based medications, not including Epidiolex if currently prescribed.
• Participant is not planning to abstain from using recreational cannabinoids or medicinal cannabis, or synthetic cannabinoid-based medications during the study.
• Female participant is pregnant (positive pregnancy test), lactating or planning pregnancy during the course of the study and for 3 months thereafter.
• Participant has any other significant disease or disorder which, in the opinion of the investigator, may either put the participant, other participants, or site staff at risk because of participation in the study, may influence the result of the study, or may affect the participant's ability to take part in the study
• Participant has diseases or disorders which are associated with liver fibrosis with a FibroScan score of ≥ 6.5 Kilopascals (where FibroScan results are available).
• Positive serology panel (including hepatitis B surface antigen and hepatitis C virus antibody) and/or positive human immunodeficiency virus antibody/p24 antigen screens at screening.
• Following a physical examination, if the participant has any abnormalities that, in the opinion of the investigator, would prevent the participant from safe participation in the study.
• Participant has significantly impaired hepatic function at Screening Visit alanine aminotransferase or aminotransferase > 3 x upper limit of normal (ULN), and total bilirubin > 2 x ULN or international normalized ratio > 1.5.
• Participant is planning to have epilepsy surgery or other major surgery within five years.
• Participant has or plans to have any medical device implanted that is contraindicated for use with FibroScan (only applicable for FibroScan subset), with the investigator consulting with the Sponsor as needed.
• Participation in any clinical trial involving an investigational medicinal product within 3 months prior to the Screening Visit or at any point during this study.

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: Cannabidiol; Cannabidiol solution 100 milligrams per milliliter (mg/mL) will be administered orally at a dose level of 5 mg/kg/day for 1 week, then increase to 10 mg/kg/day by the participant or their caregiver twice each day (morning and evening).	Drug: Cannabidiol; Oral Cannabidiol solution 100 mg/mL; Other Names: Epidiolex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Liver Fibrosis and Evaluable Fibrotic Changes as Determined and Assessed by an Independent Adjudication Committee	Screening, Day 365, Day 730, Day 1095, Day 1460, and Day 1825

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Aspartate Aminotransferase (AST) to Platelet Ratio Index	Baseline, Day 365, Day 730, Day 1095, Day 1460, and Day 1825
Change from Baseline in the Enhanced Liver Fibrosis Score	Baseline, Day 365, Day 730, Day 1095, Day 1460, and Day 1825
Change From Baseline in Fibrosis-4	Baseline, Day 365, Day 730, Day 1095, Day 1460, and Day 1825
Number of Participants With Potential Drug-Induced Liver Injury (DILI)	Day 1, Day 365, Day 730, Day 1095, Day 1460, and Day 1825
Number of Participants With Clinically Significant Clinical Laboratory Findings	Day 1, Day 365, Day 730, Day 1095, Day 1460, and Day 1825
Number of Participants With Clinically Significant Physical Examinations	Day 1, Day 365, Day 730, Day 1095, Day 1460, and Day 1825
Change From Baseline in FibroScan Scoring (FibroScan subset only)	Baseline, Day 365, Day 730, Day 1095, Day 1460, and Day 1825
Number of Participants with Severe Treatment-emergent Adverse Events (TEAEs)	Day 1, Day 365, Day 730, Day 1095, Day 1460, and Day 1825

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: Jazz Pharmaceuticals Research UK Limited

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2021
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: September 14, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Liver fibrosis; Cannabidiol; Epidiolex; Liver injury
• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms; Genetic Diseases, Inborn; Digestive System Diseases; Neurodegenerative Diseases; Liver Diseases; Congenital Abnormalities; Epilepsy, Generalized; Epilepsy; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Hamartoma; Neoplasms, Multiple Primary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Fibrosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Tuberous Sclerosis; Liver Cirrhosis; Epilepsies, Myoclonic; Lennox Gastaut Syndrome; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Cannabidiol
• Other Study ID Numbers: GWEP19022

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No