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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

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ClinicalTrials.gov Identifier: NCT04485104
Recruitment Status : Recruiting
First Posted : July 24, 2020
Last Update Posted : December 14, 2022
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

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).

Condition or disease Intervention/treatment Phase
Seizure in Participants With Tuberous Sclerosis Complex Seizure in Participants With Dravet Syndrome Seizure in Participants With Lennox-Gastaut Syndrome Drug: GWP42003-P Phase 3

Detailed Description:
The study duration will be up to approximately 62 weeks, including a 4-week screening/baseline period, a 52-week dose optimization treatment period (which includes a fixed 2-week titration period followed by flexible dose optimization), a 10-day taper period, and a safety follow-up period (4 weeks after the end-of-taper visit).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Single-arm Study to Assess the Safety, Pharmacokinetics, and Efficacy of Adjunctive Cannabidiol Oral Solution (GWP42003-P) in Participants With Tuberous Sclerosis Complex (Age 1 Month to < 2 Years of Age), Dravet Syndrome (1 Year to < 2 Years of Age), or Lennox-Gastaut Syndrome (1 Year to < 2 Years of Age) Who Experience Inadequately-controlled Seizures
Actual Study Start Date : May 19, 2021
Estimated Primary Completion Date : December 29, 2023
Estimated Study Completion Date : December 27, 2024


Arm Intervention/treatment
Experimental: GWP42003-P

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
Oral Solution
Other Names:
  • Cannabidiol
  • Epidiolex
  • Epidyolex




Primary Outcome Measures :
  1. Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  2. Mean Change From Baseline in Blood Pressure [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  3. Mean Change From Baseline in Pulse Rate [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  4. Mean Change From Baseline in Respiration Rate [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  5. Mean Change from Baseline in Body Temperature [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  6. Mean Change From Baseline in Height [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  7. Mean Change From Baseline in Body Weight [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  8. Mean Change From Baseline in Heart Rate [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  9. Mean Change From Baseline in RR Interval [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  10. Mean Change From Baseline in PR Interval [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  11. Mean Change From Baseline in QRS Duration [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  12. Mean Change From Baseline in QT Interval [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  13. Mean Change From Baseline in QTcB and QTcF [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  14. Number of Participants with a Clinically Significant Change in Laboratory Parameters [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  15. Number of Participants with Emergence of New Types of Seizures [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
  16. Plasma Concentrations of GWP42003-P and its Major Metabolites [ Time Frame: Predose, 3 hours and 6 hours post dose on Days 1, 15, 29, 57, and End of Treatment (Week 52) ]
  17. Percentage Change from Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers and Investigators [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]

Secondary Outcome Measures :
  1. Number of Treatment Responders [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]
    Treatment Responders are defined as participants with ≥ 50% reduction from baseline in caregiver- and Investigator-Reported total countable seizures

  2. Percentage Change from Baseline in Total Countable Seizures [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]

    This endpoint includes the following changes in percentage of seizures:

    • > 25% (increase);
    • ≥ 0% to ≤ 25% (increase);
    • > -25% to < 0% (reduction);
    • > -50% to ≤ -25% (reduction);
    • > -75% to ≤ -50% (reduction);
    • ≤ -75% (reduction).

  3. Number of Participants Who Achieved Seizure-Free Status [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]
  4. Percentage of Participants Still Receiving GWP42003-P [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Month to 23 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04485104


Contacts
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Contact: Clinical Trial Disclosure & Transparency 215-832-3750 ClinicalTrialDisclosure@JazzPharma.com

Locations
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United States, Arkansas
Clinical Trial Site Recruiting
Little Rock, Arkansas, United States, 72202
United States, California
Clinical Trial Site Recruiting
Los Angeles, California, United States, 90095
United States, Illinois
Clinical Trial Site Recruiting
Chicago, Illinois, United States, 60611
United States, Massachusetts
Clinical Trial Site Recruiting
Boston, Massachusetts, United States, 02114
United States, Ohio
Clinical Trial Site Recruiting
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Jazz Pharmaceuticals
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Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04485104    
Other Study ID Numbers: GWEP17005
2020-002132-67 ( EudraCT Number )
First Posted: July 24, 2020    Key Record Dates
Last Update Posted: December 14, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jazz Pharmaceuticals:
Epilepsy
Seizures
Infantile Spasms
Tumors
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
Additional relevant MeSH terms:
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Tuberous Sclerosis
Seizures
Epilepsies, Myoclonic
Lennox Gastaut Syndrome
Syndrome
Sclerosis
Disease
Pathologic Processes
Neurologic Manifestations
Nervous System Diseases
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
Genetic Diseases, Inborn
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases
Epileptic Syndromes
Cannabidiol
Anticonvulsants