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| Name | Class |
|---|---|
| Jazz Pharmaceuticals | INDUSTRY |
| Alberta Children's Hospital | OTHER |
| BC Children's Hospital Research Institute | OTHER |
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The goal of this clinical trial is to learn the best way to switch children with Lennox-Gastaut Syndrome (LGS) or Dravet Syndrome (DS) taking 'artisanal' (non pharmaceutical-grade) cannabidiol (CBD) to Epidiolex for treatment of seizures. The main questions it aims to answer are:
Researchers will examine how successful switching from 'artisanal' CBD to Epidiolex is.
Participants will:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Epidiolex Treatment | Experimental | The participant's dose of Epidiolex will be matched to their dose of 'artisanal' cannabidiol (CBD). Epidiolex will be titrated over two weeks with a concomitant taper of the participant's 'artisanal' CBD. CBD doses during transition week 1 will consist of 75% 'artisanal' and 25% Epidiolex, followed by 50% 'artisanal' and 50% Epidiolex for transition week 2. Participants will commence a CBD dose comprised of 100% Epidiolex once reaching the maintenance period of the study. Participants will remain on their matched dose of Epidiolex throughout the maintenance period, unless a dose modification is clinically indicated for efficacy, safety or tolerability. The daily dose of Epidiolex should not exceed the maximum approved dose of 20 mg/kg/day. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Epidiolex 100 mg/mL Oral Solution | Drug | The participant's 'artisanal' CBD and Epidiolex dose should be taken consistently with food or consistently without food throughout the entire study. The participant's dosing with or without food should be consistent with their method of dosing of 'artisanal' CBD prior to screening. Oral administration is recommended. When necessary, Epidiolex can be enterally administered via silicone feeding tubes, such as nasogastric or gastrostomy tubes. |
| Measure | Description | Time Frame |
|---|---|---|
| The success rate of transition of children from 'artisanal' CBD to Epidiolex. | Participants successfully transitioned from 'artisanal' CBD to Epidiolex if they complete the transition protocol and continue treatment with Epidiolex at visit 2 following the two-week transition phase of the study. The success rate will be determined as the percentage of participants that complete the two-week transition phase. | Baseline (visit 2, Day 1) through visit 4 (Day 15), the two-week transition phase. |
| Measure | Description | Time Frame |
|---|---|---|
| The acceptability rate of Epidiolex in children previously treated with 'artisanal' CBD. | Participants accepted transition to Epidiolex if they continued treatment with Epidiolex after the last scheduled visit of the maintenance period (visit 7). The acceptability rate will be determined as the percentage of participants that continue treatment with Epidiolex after the last scheduled visit of the maintenance period (visit 7, Day 85). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Short Form 12 (SF-12) score. | The Short Form 12 (SF-12) is a survey designed to assess health and well-being from a self-perspective. The questionnaire is a 12-item measure evaluating 8 areas of health: physical functioning, physical and emotional limitations, social functioning, bodily pain, general and mental health. The questionnaire will be administered to the caregiver. Higher scores represent better health-related quality-of-life. |
Inclusion Criteria:
Clinical diagnosis of Dravet Syndrome supported by:
Clinical diagnosis of Lennox Gastaut Syndrome supported by:
a. History of an EEG with slow/disorganized background and slow (<2.5 Hz or less) spike and wave activity or generalized paroxysmal fast activity (GPFA).
b. History of more than 1 type of generalized seizures, including drop seizures (tonic, atonic or tonic-clonic).
Participant must be willing and able to give written informed consent for participation. If the participant is not qualified or unable to provide written consent based on age, development, intellectual capacity or other factors, the parent or legally authorized representative must provide written informed consent on their behalf.
Must be on a stable dose of a licensed artisanal cannabidiol (CBD) product as maintenance therapy for seizure control for a minimum of 3 months prior to screening (visit 1).
'Artisanal' CBD dose must be between 5 mg/kg/day and 20mg/kg/day.
'Artisanal' CBD preparation must be a high CBD to THC formulation defined as a minimum CBD:THC ratio of 20:1.
Must be taking a minimum of 1 other anti-seizure medication (ASM) in addition to an 'artisanal' form of CBD.
Must be on a stable dose of ASMs for a minimum of 28 days prior to screening (visit 1) and remain on a stable dose throughout the entire study unless medically necessary change(s) are required for safety events.
Participants with a vagal nerve stimulator (VNS) must have the following conditions met:
Participants on the ketogenic diet must be on a stable regime for a minimum of 28 days prior to screening (visit 1) and expected to remain stable throughout the entire study.
Participant and/or caregiver must be willing to maintain a seizure diary throughout the duration of the study.
Exclusion Criteria:
Previous or current exposure to Epidiolex.
Supplemental use of cannabinoid-containing products, including but not limited to:
Pregnant or breastfeeding.
Any clinically significant, unstable medical condition other than epilepsy that, in the opinion of the investigator, could place the participant at increased risk or interfere with the results of the study.
Hepatic impairment at screening (visit 1) defined as either of the following conditions:
Known sensitivity to any ingredient in Epidiolex, including sesame and sesame oil.
Unwillingness to refrain from alcohol consumption throughout the duration of the study.
Unwillingness of females of childbearing potential to use a highly effective form of birth control. Acceptable methods include: hormonal contraceptives, intra-uterine devices, bilateral tube occlusion, vasectomized partner and sexual abstinence.
Currently enrolled in another clinical trial.
Have suicidal plan/intent, active suicidal thoughts, or a suicide attempt in the past 6 month prior to screening.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Laura MacDougall, PhD | Contact | 416-813-7996 | laura.macdougall@sickkids.ca |
| Name | Affiliation | Role |
|---|---|---|
| Elizabeth Donner, MD | The Hospital for Sick Children | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
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| ID | Term |
|---|---|
| D004831 | Epilepsies, Myoclonic |
| D065768 | Lennox Gastaut Syndrome |
| D012640 | Seizures |
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D004829 | Epilepsy, Generalized |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D002185 | Cannabidiol |
| D012996 | Solutions |
| ID | Term |
|---|---|
| D002186 | Cannabinoids |
| D013729 | Terpenes |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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|
| Baseline (visit 2, Day 15) to end of treatment (visit 7, Day 85). |
| The change in seizure frequency following transition of children from 'artisanal' CBD to Epidiolex. | The percent change (increase or decrease) from baseline in 28-day seizure frequency during the maintenance period. Seizure frequency will be calculated as the total number of seizures divided by the number of days with seizure data, multiplied by 28. | Baseline (visit 2, Day 1) through the end of treatment (visit 7, Day 85). |
| Change in reported Pediatric Epilepsy Side-Effects Questionnaire (PESQ) score. | The Pediatric Epilepsy Side Effects Questionnaire (PESQ) is a rating scale to assess pediatric participant-reported side effects associated with anti-seizure medication treatment. Each side-effect is rated on a 6-point Likert scale as follows: (1) - "Not present", (2) - "Low severity", (3) - "Low-moderate severity", (4) - "Moderate severity", (5) - "Moderate-high severity", (6) - "High severity". Higher scores indicated worse side-effects. | Baseline (visit 2, Day 1) through visit 4 (Day 15), visit 5 (Day 29) and end of treatment (visit 7, Day 85). |
| Change Clinical Global Impression of Improvement (CGI-I) score. | The Clinical Global Impression of Improvement (CGI-I) is a 7-point Likert scale used to rate the overall change in seizure control, behaviour, safety and tolerability after transitioning to Epidiolex relative to baseline. The participant's overall improvement is rated by the clinician and caregiver as: 1- "very much improved", 2- "much improved', 3- "minimally improved", 4- "no change", 5- "minimally worse", 6- "much worse", and 7- "very much worse". Higher scores indicate worse condition. | Baseline (visit 2, Day 1) through visit 5 (Day 29) and end of treatment (visit 7, Day 85). |
| Change in Clinical Global Impression of Seizure Intensity/Duration (CGI-CSID) score. | The Clinical Global Impression of Change in Seizure Intensity/Duration (CGI-CSID) is a 7-point Likert scale used to rate the overall change in seizure intensity and/or duration after transitioning to Epidiolex relative to baseline. The participant's overall improvement is rated by the clinician and caregiver as: 1- "very much improved", 2- "much improved', 3- "minimally improved", 4- "no change", 5- "minimally worse", 6- "much worse", and 7- "very much worse". Higher scores indicate worse condition. | Baseline (visit 2, Day 1) through visit 5 (Day 29) and end of treatment (visit 7, Day 85). |
| Change in Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) score. | The Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) is a caregiver-reported questionnaire that evaluates quality of life in epileptic children. It contains 55 questions that measure quality of life in 4 areas: cognitive functioning, emotional functioning, social functioning, and physical functioning. Each question is rated on a 5-point Likert scale, with the option to answer "not applicable" as follows: (1) - "All of the time", (2) - "Most of the time", (3) - "Some of the time", (4) - "A little of the time", (5) - "None of the time", (6) - Not applicable. Higher scores indicate higher health-related quality of life. | Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85). |
| Change in Measure Yourself Medical Outcome Profile 2 (MYMOP2) score. | The Measure Yourself Medical Outcome Profile 2 (MYMOP2) questionnaire is a scale that allows participants or caregivers to identify the problem(s) that are most important to them/the participant, and rate the severity of the problem (s) on a 7-point Likert scale ranging from 0 (as good as it can be) to 6 (as bad as it could be). Higher scores indicate worse problems. | Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85) |
| Change in Children's Sleep Habit Questionnaire (CSHQ) score. | The Children's Sleep Habit Questionnaire (CSHQ) is a caregiver-reported questionnaire to measure sleep behaviours in children. The questionnaire has 45 questions about bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. Each question is rated on a 3-point Likert scale as follows: (1) - "Usually (5 or more times in a week)", (2) - "Sometimes (2-4 times in a week)", (3) - Rarely (never or 1 time during a week). A higher score indicates more sleep problems. | Baseline (visit 2, Day 1) through visit 5 (Day 29) and end of treatment (visit 7, Day 85). |
| Number of dose increases in anti-seizure medications (ASMs) after starting Epidiolex. | The number of dose increases in anti-seizure medications (ASMs), including Epidiolex, due to worsening seizure burden or other factors. | Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85). |
| Number of dose decreases in anti-seizure medications (ASMs) after starting Epidiolex. | The number of dose increases in anti-seizure medications (ASMs), including Epidiolex, due to adverse events or other factors. | Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85). |
| Frequency of adverse events of special interest (AESIs) after starting Epidiolex. | Adverse events of special interest (AESIs) include: somnolence, sedation, appetite changes, gastro-intestinal upset (including diarrhea and vomiting), and transaminase elevations. Frequency of AESIs will be measured by determining the total number of AESIs experienced throughout the treatment period of the study. | Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85). |
| Severity of adverse events of special interest (AESIs) after starting Epidiolex. | Adverse events of special interest (AESIs) include: somnolence, sedation, appetite changes, gastro-intestinal upset (including diarrhea and vomiting), and transaminase elevations. The severity of AESIs will be assessed as: "Mild - Events require minimal or no treatment and do not interfere with the participant's daily activities", "Moderate - Events result in a low level of inconvenience or concern", or "Severe - Events interrupt a participant's usual daily activity and may require therapy or other treatment". The total number of mild, moderate and severe AESIs experienced throughout the treatment period of the study will be determined. | Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85). |
| Duration of adverse events of special interest (AESIs) after starting Epidiolex. | Adverse events of special interest (AESIs) include: somnolence, sedation, appetite changes, gastro-intestinal upset (including diarrhea and vomiting), and transaminase elevations. The duration of AESIs will be measured by calculating the length of individual AESIs experienced throughout the treatment period of the study. | Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85). |
| Withdrawal rate due to adverse events after starting Epidiolex. | The withdrawal rate will be determined as the percentage of participants who withdraw from the study and discontinue Epidiolex due to adverse events. | Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85). |
| The change in frequency of seizure rescue medication use following transition from 'artisanal' CBD to Epidiolex. | The percent change (increase or decrease) from baseline in 28-day seizure rescue medication use during the maintenance period. Rescue medication frequency will be calculated as the total number of doses of rescue medication administered divided by the number of days with diary data, multiplied by 28. | Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85). |
| Change in Columbia-Suicide Severity Rating Scale (C-SSRS) score. | The Columbia-Suicide Severity Rating Scale (C-SSRS) assess the risk of suicidal ideation and behaviour. The questions are divided into categories related to ideation (thoughts) and behaviour (actions). Higher scores indicate more serious/worse suicidal ideation or behaviors. | Baseline (visit 1, Day -28) through end of treatment (visit 7, Day 85). |
| Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85). |
| Motivation for switching from 'artisanal' CBD to Epidiolex. | The switching questionnaire consists of two multiple choice questions, along with an open-ended question designed to understand the caregiver's primary and secondary reasons for transitioning their child from 'artisanal' CBD to Epidiolex. | Baseline (visit 1, Day -28), once at beginning of study. |
| D000073376 | Epileptic Syndromes |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004364 |
| Pharmaceutical Preparations |