Assessment of Adjunctive Cannabidiol Oral Solution (GWP42003-P) in Children With Tuberous Sclerosis Complex (TSC), Dravet Syndrome (DS), or Lennox-Gastaut Syndrome (LGS) Who Experience Inadequately-controlled Seizures

NCT04485104 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: GWEP170052020-002132-67
• Study Type: interventional
• Target: 3
• Locations: 3 countries
• Sites: 11

Brief Summary

This study will be conducted to evaluate the safety, pharmacokinetics (PK), and efficacy of adjunctive GWP42003-P in participants \< 2 years of age with tuberous sclerosis complex (TSC), Lennox-Gastaut syndrome (LGS), or Dravet syndrome (DS).

Conditions

Seizure in Participants With Tuberous Sclerosis Complex; Seizure in Participants With Dravet Syndrome; Seizure in Participants With Lennox-Gastaut Syndrome

Keywords

Epilepsy; Seizures; Infantile Spasms; Pediatric; Children; Infants; Cannabidiol oral solution; GWP42003-P; Tuberous Sclerosis Complex; TSC; Tuberous Sclerosis; Cannabidiol; Epidiolex; CBD; Seizure; Child; TSC1; TSC2; Tuberous Sclerosis 1; Tuberous Sclerosis 2; Lennox-Gastaut Syndrome; Dravet Syndrome

Outcome Measures

Primary Outcomes (19)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From start of treatment to the post-treatment safety follow-up visit, up to 62 weeks

• Mean Change From Baseline in Blood Pressure

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in Pulse Rate

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in Respiratory Rate

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in Body Temperature

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in Height

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in Body Weight

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in Heart Rate

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in RR Interval

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in PR Interval

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in QRS Duration

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in QT Interval

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Mean Change From Baseline in QTcB and QTcF

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Number of Participants With a Clinically Significant Change in Laboratory Parameters

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Number of Participants With Emergence of New Types of Seizures

  From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks

• Plasma Concentrations of GWP42003-P and Its Major Metabolites

  Predose, 3 hours and 6 hours post dose at End of Treatment (Week 52)

• Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers

  Day 1 up to Taper Period, up to Week 52

• Clinician Global Impression of Severity (CGI/S) Score

  The CGIC/S is a comprehensive neurodevelopmental assessment that covers the following domains: sensory, motor, cognition, emotional/behavioral health, communication, social, and adaptive functioning. This assessment is a 2-question survey per domain to be completed by the clinician. Individual domain scores are reported. The severity of impairment in each domain is rated by the clinician in a scale of 1 through 7 where 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill. Higher scores indicate poor clinical outcome.

  At Day 365 (EOT)

• Clinician Global Impression of Change (CGI/C) Score

  The CGI/C is a comprehensive neurodevelopmental assessment that covers the following domains: sensory, motor, cognition, emotional/behavioral health, communication, social, and adaptive functioning. This assessment is a 2-question survey per domain to be completed by the clinician. Individual domain scores are reported. The severity of impairment in each domain is rated by the clinician in a scale of 1 through 7 where 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill. Higher scores indicate poor clinical outcome.

  At Day 365 (EOT)

Secondary Outcomes (3)

• Number of Treatment Responders

  Day 1 up to the taper period, up to Week 52

• Number of Participants Who Achieved Seizure-Free Status

  Week 12, and every 4 weeks thereafter, up to date of withdrawal or Week 24, whichever occurs first

• Percentage of Participants Still Receiving GWP42003-P

  Week 12, and every 4 weeks thereafter, up to date of withdrawal or Week 24, whichever occurs first

Other Outcomes (2)

• Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score

  At Day 365 (EOT)

• Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers

  Day 1 up to Taper Period, up to Week 52

Study Arms (1)

GWP42003-P

EXPERIMENTAL

The 52-week treatment period includes a fixed 2-week titration schedule followed by flexible dose optimization. Day 1: 5 mg/kg/day (2.5 mg/kg twice daily (b.i.d.)) Day 8: 10 mg/kg/day (5 mg/kg b.i.d.) Day 15 to Week 52: Flexible dosing based on the participant's observed efficacy, safety, and tolerability per the investigator's clinical judgement. Up to a maximum of 20 mg/kg/day (10 mg/kg b.i.d.) for LGS and DS or 25 mg/kg/day (12.5 mg/kg b.i.d.) for TSC, in maximum weekly increments of 5 mg/kg/day (≤ 2.5 mg/kg b.i.d.).

Drug: GWP42003-P

Interventions

GWP42003-P DRUG

Oral Solution

Also known as: Cannabidiol, Epidiolex, Epidyolex

GWP42003-P

Eligibility Criteria

• Age: 1 Month - 23 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants with TSC (1 month to \< 2 years of age), or DS (1 year to \< 2 years of age), or LGS (1 year to \< 2 years of age) within the specified age range at the time of initial informed consent.
• Parent(s)/legal representative is/are willing and able to give informed consent for participation in the study.
• Parent(s)/legal representative is/are willing and able (in the investigator's opinion) to comply with all study requirements (including accurate electronic participant-reported outcome \[ePRO\] diary completion).
• Participants with TSC must have a diagnosis per the 2012 International Tuberous Sclerosis Complex Consensus Conference. Participants with LGS or DS must have a diagnosis that is consistent with International League Against Epilepsy (ILAE) guidelines and confirmed by the Epilepsy Study Consortium (ESCI).
• Participants who have uncontrolled seizures, and who are currently receiving 1 or more antiseizure medication (ASMs).
• A suitable VEEG, as available in the medical record, within 1 year of Visit 1. When a historical VEEG is not available, and if clinically indicated and appropriate (due to uncertainties or new seizures), a VEEG will be completed and read to confirm diagnosis prior to Visit 3. All VEEGs are to be read at baseline by the investigator and by an independent reviewer.
• Has seizures which are not adequately controlled through their current ASMs, defined as ≥ 1 seizure reported on the seizure diary during the screening/baseline period

You may not qualify if:

• Has tumor growth which, in the opinion of the investigator, could affect participant safety.
• Has clinically significant abnormal laboratory values, in the investigator's opinion, at screening/baseline.
• Has clinically significant abnormalities in the electrocardiogram (ECG) measured at screening/baseline.
• Has any concurrent cardiovascular conditions, that will, in the investigator's opinion, interfere with the ability to assess their ECGs.
• Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the study intervention such as sesame seed oil.
• Has significantly impaired hepatic function prior to Visit 3, defined as:
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × upper limit of normal (ULN) and (total bilirubin \[TBL\] \> 2 × ULN or international normalized ratio \[INR\] \> 1.5).
• Serum ALT or AST \> 5 × ULN.
• Serum ALT or AST \> 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (\> 5%).
• Elevated ALT or AST should be discussed with the medical monitor prior to Visit 3; the medical monitor may allow for a confirmatory re-draw prior to Visit 3.
• Has received another study intervention within 4 weeks prior to Visit 1 or plans to take another study intervention during the study.
• Has any other clinically 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.
• Any clinically significant abnormalities identified following a physical examination of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if they took part in the study.
• Has previously been enrolled into this study.
• Has plans to travel outside their country of residence during the study, unless the participant has confirmation that the study intervention is permitted in the destination country.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• Jazz Pharmaceuticals Research UK Limited: collaborator

Study Sites (11)

Clinical Trial Site

Little Rock, Arkansas, 72202, United States

Location

Clinical Trial Site

Los Angeles, California, 90095, United States

Location

Clinical Trial Site

Chicago, Illinois, 60611, United States

Location

Clinical Trial Site

Boston, Massachusetts, 02114, United States

Location

Clinical Trial Site

Cincinnati, Ohio, 45229, United States

Location

Clinical Trial Site

Houston, Texas, 77030, United States

Location

Clinical Trial Site

Florence, 50139, Italy

Location

Clinical Trial Site

Genova, 16147, Italy

Location

Clinical Trial Site

Rome, 00165, Italy

Location

Clinical Trial Site

Barcelona, 08950, Spain

Location

Clinical Trial Site

Madrid, 28034, Spain

Location

MeSH Terms

Conditions

Epilepsy; Seizures; Spasms, Infantile; Tuberous Sclerosis; Tuberous Sclerosis 1; Tuberous Sclerosis 2; Lennox Gastaut Syndrome; Epilepsies, Myoclonic

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Epilepsy, Generalized; Epileptic Syndromes; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Three participants were enrolled. There was not enough information to answer the research questions. The limited data collected were not enough to provide meaningful conclusions regarding the efficacy, safety, and PK of CBD-OS in this clinical trial.

Results Point of Contact

• Title: Director Clinical Trial Disclosure & Transparency
• Organization: Jazz Pharmaceuticals, Inc.

ClinicalTrialDisclosure@JazzPharma.com

+1 215-832-3750

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: July 24, 2020
• Study Start: May 19, 2021
• Primary Completion: January 28, 2025
• Study Completion: January 28, 2025
• Last Updated: October 31, 2025
• Results First Posted: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

IT (3); ES (2); US (6)