Epidiolex for Epilepsy

(CANN-SWITCH Trial)

Overseen By Laura MacDougall, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Elizabeth Donner

Must be taking: Artisanal CBD, Anti-seizure medications

Must not be taking: Cannabis, Epidiolex

Disqualifiers: Pregnancy, Hepatic impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best method to switch children with specific epilepsy types, such as Dravet or Lennox-Gastaut Syndrome, from homemade CBD to Epidiolex, a prescription cannabidiol medication, for improved seizure control. Researchers aim to determine if a gradual switch is effective, whether the same dose is sufficient, and what side effects might occur. The trial suits children who have used a stable dose of homemade CBD for at least three months and are also on other epilepsy medications. Participants will transition from CBD to Epidiolex over two weeks, visit the clinic five times in 20 weeks, and maintain a diary of seizures and symptoms. As a Phase 4 trial, this study focuses on an FDA-approved treatment, aiming to understand how Epidiolex can benefit more patients.

Do I have to stop taking my current medications for the trial?

You will not have to stop taking your current anti-seizure medications, but you will need to gradually switch from 'artisanal' CBD to Epidiolex. Your other medications should remain stable unless a change is needed for safety reasons.

What is the safety track record for Epidiolex?

Previous studies have shown that Epidiolex is generally well-tolerated by people with epilepsy. Research indicates that while 9.7% of patients experienced some side effects, these were mostly mild. Most people taking Epidiolex did not encounter serious problems.

Additionally, a strong 18-month retention rate suggests that many patients continue using Epidiolex for an extended period without major issues. Caregivers report plans to keep using it because it helps reduce seizures and improves quality of life.

Overall, the evidence suggests that Epidiolex is a safe option for treating epilepsy, with most side effects being manageable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Epidiolex is unique because it is the first FDA-approved treatment derived from cannabidiol (CBD) for epilepsy. Unlike standard treatments for epilepsy, which often involve traditional anti-seizure medications, Epidiolex uses a purified form of CBD to help manage seizures. Researchers are excited about Epidiolex because it offers a potential new mechanism of action by targeting the endocannabinoid system, which is different from how most epilepsy medications work. This could provide a new option for patients who have not responded well to conventional treatments.

What is the effectiveness track record for Epidiolex in treating epilepsy?

Research has shown that Epidiolex helps reduce seizures in people with epilepsy. In this trial, participants will receive Epidiolex, which studies have found can lead to a 44% decrease in monthly drop seizures when taken at a dose of 20 mg per kilogram of body weight each day. Another study reported that seizure reductions ranged from 54% to 92%, depending on the type of seizure. Most people tolerate Epidiolex well and continue using it long-term. This medication is already approved for treating conditions like Lennox-Gastaut Syndrome and Dravet Syndrome. ^{5 6 7 8 9}

Who Is on the Research Team?

Elizabeth Donner, MD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

This trial is for children with Lennox-Gastaut Syndrome or Dravet Syndrome who are currently using 'artisanal' CBD to treat seizures. They will be transitioning to Epidiolex, a pharmaceutical-grade CBD. The study requires clinic visits and diary keeping over 20 weeks.

Inclusion Criteria

I am currently taking another seizure medication besides artisanal CBD.

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

Pregnant or breastfeeding

Have suicidal plan/intent, active suicidal thoughts, or a suicide attempt in the past 6 month prior to screening

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transition

Participants gradually increase their dose of Epidiolex and reduce their dose of 'artisanal' CBD until they are taking just Epidiolex

2 weeks

2 visits (in-person)

Maintenance

Participants remain on their matched dose of Epidiolex throughout the maintenance period, unless a dose modification is clinically indicated

11 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epidiolex

Trial Overview The study tests the effectiveness of switching from 'artisanal' CBD to Epidiolex in managing seizures. It evaluates how well a gradual transition works, if the same dose is effective, and monitors any side effects during the process.

How Is the Trial Designed?

Group I: Epidiolex Treatment Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Elizabeth Donner

Lead Sponsor

Alberta Children's Hospital

Collaborator

Trials

58

Recruited

44,700+

BC Children's Hospital Research Institute

Collaborator

Trials

14

Recruited

2,800+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

The long-term efficacy and safety of four third-generation antiepileptic drugs (AEDs) - lacosamide, perampanel, eslicarbazepine acetate, and brivaracetam - were confirmed in extension studies, showing patient retention rates of 75-80% at one year and 36-68% at two years.

These newer AEDs offer improved tolerability and safety profiles compared to older medications, with no major safety risks identified and specific adverse effects like hyponatremia noted, making them valuable options for treating refractory focal onset seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment. Kwok, CS., Johnson, EL., Krauss, GL.[2021]

Common treatment-emergent adverse events (TEAEs) in pediatric epilepsy patients include somnolence, sedation, and behavioral changes, which are frequently associated with various antiepileptic drugs (AEDs).

Among the AEDs studied, Lamotrigine, Gabapentin, Oxcarbazepine, and Levetiracetam are noted for their good tolerability, with withdrawal rates of 2% or less, while Tiagabine and Everolimus have higher discontinuation rates due to intolerable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability profile of new antiepileptic drug treatment in children with epilepsy. Moavero, R., Pisani, LR., Pisani, F., et al.[2019]

In a study of 309 epilepsy patients in Poland, 73.8% reported at least one adverse event (AE) while on antiepileptic drugs (AEDs), with cognitive disturbances, psychological issues, and sedation being the most common AEs.

Treatment modifications occurred in 22.3% of patients, primarily due to lack of efficacy (10.7%) and adverse events (5.2%), highlighting the need for careful monitoring of AED effectiveness and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern of adverse events of antiepileptic drugs: results of the aESCAPE study in Poland. Chmielewska, B., Lis, K., Rejdak, K., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36893722/

Real-world, long-term evaluation of the tolerability and ... Epidiolex® is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022510X23001739

Quality improvement study in epilepsy patients treated with ... Initial studies with Epidiolex® showed a significant reduction in median seizure frequency (from a 26.6% to a 44.2% average reduction) in ...

3. epidiolex.com epidiolex.com/epidiolex-results

Seizure Treatment & Study Results In another study, there was a 44% monthly reduction in drop seizures among patients taking EPIDIOLEX in the 20 mg/kg/day group, compared with a 22% reduction ...

4. neurology.org neurology.org/doi/10.1212/WNL.0000000000206411

Long-term Effectiveness of Cannabidiol (CBD) Against ... CBD treatment was associated with median reductions of 54%–88% (overall focal seizures), 56%–84% (FAS), 54%–92% (FIAS), and 52%–74% (FBTCS) ...

5. practicalneurology.com practicalneurology.com/news/adjunctive-therapy-with-epidiolex-was-effective-for-treatment-resistant-focal-epilepsy-in-a-real-world-setting/2470657/

Adjunctive Epidiolex Shows Real-World Effectiveness for ... Participants treated with Epidiolex showed significant reductions in focal and total seizures through 144 weeks, with 93% of participants ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12446575/

Assessing Real World Efficacy, Safety, and 18‐Month ... Conclusions. CBD reduced seizures and improved non seizures' morbidities in drug‐resistant epilepsy. Strong 18‐month retention rate, including ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2803957

Adverse Events of Cannabidiol Use in Patients With Epilepsy Results Nine studies were included. Overall incidences of 9.7% in the CBD group and 4.0% in the control group were found for any grade AEs.

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/epi.18496?af=R

Long‐term efficacy and safety of cannabidiol in patients ... CBD treatment resulted in a comparable reduction in focal seizure frequency of 51%–87% in the TSC group and 46–75% in the non-TSC group.

9. sciencedirect.com sciencedirect.com/science/article/pii/S092012112300205X

Caregiver-reported outcomes with real-world use of ... Overall, 93% of caregivers reported planning to continue CBD treatment, primarily because of reduced seizure burden but also because of improvements in ...