A Study to Investigate the Effect of Gradual Titration to Optimize Cannabidiol Treatment in Adults With LGS

Phase 4Not Yet RecruitingNCT07728097

Jazz Pharmaceuticals40 enrolled

Overview

This is a Phase 3b/Phase 4 study. The purpose of this study is to learn more about the efficacy of using CBD-OS as an add-on therapy for the treatment of LGS in adults.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lennox-Gastaut Syndrome

Interventions

Cannabidiol Oral SolutionDRUG

100 mg/ml Cannabidiol Oral solution (CBD-OS)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Has a confirmed clinical diagnosis of LGS with a history of seizures and actively experiencing seizures within 6 months of screening. 2. Is naïve to CBD-OS treatment or has been off CBD-OS treatment for at least 3 months prior to screening. 3. Is willing to maintain any factors expected to affect seizures (eg, alcohol consumption, smoking, concomitant medication usage) stable for the duration of the study. 4. Is currently treated with at least 1 ASM, but no more than 3 ASMs, and is on a stable regimen for at least 4 weeks prior to screening. 5. Adequate contraceptive precautions 6. Participant has a primary caregiver/legally authorized representative (LAR) who is willing and able, in the investigator's opinion, to participate throughout the duration of the study and to comply with all study requirements 7. Experienced at least 4 or more countable major motor seizures (isolated seizures or seizures occurring in a cluster) during the 5-week Baseline Period preceding treatment. 8. Caregiver completed at least 80% of seizure diary entries during the Baseline Period with no more than 3 consecutive days of missing entries. Exclusion Criteria: 1. Has a significant psychiatric illness 2. Has an illness during the 4 weeks prior to screening other than epilepsy which, in the investigator's opinion, could affect study outcomes or seizure frequency. 3. Has history of SE in the 3 months prior to screening. 4. Has any other significant disease other than epilepsy, which, in the investigator's opinion, 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. 5. Has previously undergone significant surgery for epilepsy in the 6 months prior to screening or planned to undergo surgery for epilepsy during the study. 6. Is currently using or has in the past used recreational or medicinal cannabis or synthetic cannabinoid-based medications, products, or supplements within the 3 months prior to screening and is not willing to undergo a 1-month washout period before being rescreened. 7. Has initiated felbamate within the 12 months prior to screening. 8. Is not willing to adjust dosage of CBD-OS if needed when using strong inducers of CYP3A4 and/or strong inducers of CYP2C19 concomitantly with CBD-OS 9. Previously discontinued cannabidiol due to severe adverse events (SAE), hypersensitivity or lack of efficacy 10. Has clinically significant abnormal lab values 11. Has clinically impaired hepatic or renal function 12. History of, current risk or presence of actual suicidal ideations 13. Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of CBD-OS, such as sesame oil. 14. Has a known or suspected history of alcohol or substance abuse disorder 15. Is currently consuming, and unwilling to stop consumption, or planning to consume tonic water on a regular basis throughout the study.

Locations (1)

Louisiana State University Health Sciences Center New Orleans

New Orleans, Louisiana, United States

Outcomes

Primary Outcomes

Percentage of participants reporting 50% or more reduction in their 28-day average countable major motor seizure frequency

Time frame: End of Treatment Period, Week 24

Secondary Outcomes

Retention Rate

Retention Rate is defined as percentage of participants completing or continuing CBD-OS treatment at different timepoints in the study

Time frame: At Weeks 8, 12, 16 and 24

Percentage of participants experiencing worsening, change, no change or improvement in in their 28-day average countable major motor and total seizure frequency

As reported in participants' electronic diaries

Time frame: Baseline to Week 4, Baseline to Week 8, Baseline to Week 12, Baseline to Week 16, Baseline to Week 24

Percentage of participants considered treatment responders

Treatment responders will be categorized as those experiencing a 50% or more reduction, a 75% or more reduction or 100% reduction in their 28-day average seizure frequency as reported in participants' electronic diaries

Time frame: Baseline to Week 4, Baseline to Week 8, Baseline to Week 12, Baseline to Week 16, Baseline to Week 24

Change in 28-day average frequency of countable major motor and total seizures

Assessed per 28 days from electronic diary entries

Time frame: Baseline to Week 4, Baseline to Week 8, Baseline to Week 12, Baseline to Week 16, Baseline to Week 24

Change in number of seizure-free days

Assessed per 28 days from electronic diary entries

Time frame: Baseline to Week 4, Baseline to Week 8, Baseline to Week 12, Baseline to Week 16, Baseline to Week 24

Central Contacts

Clinical Trial Disclosure & Transparency

CONTACT

215-832-3750 ClinicalTrialDisclosure@JazzPharma.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Change in CaGI-S severity of seizure scores

Caregiver Global Impression of Severity (CaGI-S) is a single-item, 5-point Likert-type rating scale (ranging from 0 "not severe at all" to 5 "very severe"). Using this scale, caregivers will be asked to rate their impression of the participant's severity of seizures, and the severity of the impact caused by the seizure.

Time frame: Baseline to Week 16, Baseline to Week 24

Change in CaGI-S severity of impact of seizures scores

Time frame: Baseline to Week 16, Baseline to Week 24

Change in VAS scores

Visual Analog Scale (VAS) is a caregiver-reported tool used to quantify the severity of impact of subjective non-seizure symptoms and assesses sleep, communication, and disruptive behavior. The VAS enables sensitive detection of changes in non-seizure domains (disruptive behavior, Sleep, and Communication) important to patients with LGS and their caregivers. The VAS has a total score ranging from 0 to 100 with the higher score indicating worse conditions.

Time frame: Baseline to Week 16, Baseline to Week 24

Change in CaGI-S severity of level of alertness scores

CaGI-S Alertness is a caregiver single item assessment on a 5-point Likert-type rating scale (ranging from 0 "not severe at all" to 5 "very severe") assessing their impression of participant's severity of level of awareness

Time frame: Baseline to Week 16, Baseline to Week 24

Change in CaGI-S severity of overall condition scores

CaGI-S Overall Condition is a caregiver single item assessment on a 5-point Likert-type rating scale (ranging from 0 "not severe at all" to 5 "very severe") assessing their impression of participant's severity of overall condition

Time frame: Baseline to Week 16, Baseline to Week 24

CaGI-C level of alertness scores

Caregiver Global Impression of Change (CaGI-C) Alertness is a caregiver single item assessment on a 7-point Likert-type rating scale (ranging from 1 "very much improved" to 7 "very severe") assessing their impression of participant's severity of level of awareness

Time frame: At Week 16, at week 24

CaGI-C overall condition scores

Caregiver Global Impression of Change (CaGI-C) overall condition is a caregiver single item assessment on a 7-point Likert-type rating scale (ranging from 1 "very much improved" to 7 "very severe") assessing their impression of participant's severity of overall condition

Time frame: At Week 16, at week 24

Change in CGI-S overall condition scores

Clinician Global Impression of severity (CGI-S) Overall Condition is a clinician single item assessment on a 5-point Likert-type rating scale (ranging from 1 "not severe at all" to 5 "very severe") assessing their impression of participant's severity of level of overall condition

Time frame: Baseline to Week 16, Baseline to Week 24

CGI-C overall condition scores

Clinician Global Impression of Change (CGI-C) Overall Condition is a clinician single item assessment on a 7-point Likert-type rating scale (ranging from 1 "very much improved" to 5 "very much worse") assessing their impression of participant's change of overall condition

Time frame: At Week 16, At Week 24

Change in ELDQOL Behavior subscale scores

Epilepsy and Learning Disabilities Quality of Life (ELDQOL) is designed for the caregiver to rate the quality of life (QOL) in children with severe epilepsy and learning disabilities over the last month. The questionnaire has a total of 28 main questions, grouped into 4 subscales: behavior, seizure severity, mood, and side effects. The ELDQOL behavior subscale includes 9 of the 28 total main questions with a total score ranging from 9 to 36 with the higher score indicating greater behavioral problems

Time frame: Baseline to Week 16, Baseline to Week 24

Change in ELDQOL seizure severity subscale scores

Epilepsy and Learning Disabilities Quality of Life (ELDQOL) is designed for the caregiver to rate the quality of life (QOL) in children with severe epilepsy and learning disabilities over the last month. The questionnaire has a total of 28 main questions, grouped into 4 subscales: behavior, seizure severity, mood, and side effects. The ELDQOL seizure severity subscale includes 14 of the 28 total main questions with a total score ranging from 10 to 56 with the higher score indicating greater seizure severity

Time frame: Baseline to Week 16, Baseline to Week 24

Change in ELDQOL mood scale subscale scores

Epilepsy and Learning Disabilities Quality of Life (ELDQOL) is designed for the caregiver to rate the quality of life (QOL) in children with severe epilepsy and learning disabilities over the last month. The questionnaire has a total of 28 main questions, grouped into 4 subscales: behavior, seizure severity, mood, and side effects. The ELDQOL mood scale subscale includes 1 of the 28 total questions with a total score ranging from 16 to 64 with the higher score indicating greater mood problems

Time frame: Baseline to Week 16, Baseline to Week 24

Change in ELDQOL side-effects profile subscale scores

Epilepsy and Learning Disabilities Quality of Life (ELDQOL) is designed for the caregiver to rate the quality of life (QOL) in children with severe epilepsy and learning disabilities over the last month. The questionnaire has a total of 28 main questions, grouped into 4 subscales: behavior, seizure severity, mood, and side effects. The ELDQOL side-effects profile subscale includes 2 of the 28 total main questions with a score ranging from 19 to 76 with the higher score indicating greater side effects

Time frame: Baseline to Week 16, Baseline to Week 24

Number of participants reporting adverse events leading to discontinuation

Time frame: Up to week 24

Time the adverse events started from baseline

Time frame: Up to week 24

Number of Participants with Abnormal Laboratory Values

Time frame: Up to week 24

Change in suicidal ideation scores

As evaluated by the Columbia-Suicide Severity Rating Scale (C-SSRS). The questionnaire has a total score ranging from 0 to 5 with a score of 0 indicating no suicidal ideation is present.

Time frame: Baseline, up to week 24

Change in number of suicide attempts

As per the response in the C-SSRS

Time frame: Baseline, up to week 24

Percentage of participants requiring inpatient hospitalization due to epilepsy

Time frame: Up to week 24

Change in number of usage of rescue medication

Time frame: Baseline, Up to week 24