Cannabidiol for Seizures

Recruiting at11 trial locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: GW Research Ltd

Stay on Your Current Meds

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a medication called GWP42003-P in children under 2 years old who have severe seizure disorders like TSC, LGS, or DS. The study will last over a year and will check if the medication is safe, how it moves through the body, and if it helps reduce seizures. These conditions often don't respond well to usual treatments, so new options are needed. Cannabidiol (pharmaceutical) is approved by the FDA for the treatment of seizures associated with DS, Lennox-Gastaut syndrome, and tuberous sclerosis complex in patients ≥1 year of age.

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

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants must have uncontrolled seizures while on their current antiseizure medications, suggesting you may continue them.

What data supports the idea that Cannabidiol for Seizures is an effective drug?

The available research shows that Cannabidiol (CBD) is effective in reducing seizures for people with certain types of epilepsy, like Lennox-Gastaut syndrome and Dravet syndrome. In studies, patients who took CBD along with their usual treatment had fewer seizures compared to those who did not add CBD. For example, in some trials, patients who received CBD had better outcomes in terms of seizure frequency than those who only received their current treatment without CBD. This suggests that CBD can be a helpful addition to existing treatments for these conditions. ^{1 2 3 4 5}

What safety data is available for CBD in treating seizures?

Safety data for cannabidiol (CBD), marketed as Epidiolex, includes findings from various studies. Common side effects reported are somnolence and diarrhea. There are known drug interactions, such as with lithium, which can lead to toxicity. Long-term studies show that CBD is generally well-tolerated in children with treatment-resistant epilepsy, with a study retention rate of 77% at one year. Adverse events decreased over time in a prospective study, indicating improved tolerability. ^{4 6 7 8 9}

Is the drug Cannabidiol promising for treating seizures?

Yes, Cannabidiol (CBD) is a promising drug for treating seizures, especially in conditions like Dravet syndrome and Lennox-Gastaut syndrome. It has been shown to reduce seizures effectively in several studies and has been approved for use in Europe and the United States. ^{2 4 10 11 12}

Research Team

Eligibility Criteria

This trial is for children under 2 years old with TSC, LGS, or DS who have seizures not well-controlled by current medications. They must be diagnosed according to specific guidelines and their caregivers should consent and comply with study requirements. Children with certain health issues or hypersensitivity to cannabinoids are excluded.

Inclusion Criteria

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)

I have seizures that aren't controlled even though I'm on medication.

Exclusion Criteria

Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the study intervention such as sesame seed oil

Has previously been enrolled into this 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

Treatment Details

Interventions

• GWP42003-P (Cannabidiol)

Trial Overview The trial tests GWP42003-P, a cannabidiol oral solution as an additional treatment for young children with TSC, LGS, or DS experiencing poorly controlled seizures. It aims to assess the safety, how the body processes the drug (pharmacokinetics), and its effectiveness.

Participant Groups

Group I: GWP42003-P Experimental Treatment 1 Intervention

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.).

Who Is Running the Clinical Trial?

GW Research Ltd

Lead Sponsor

Trials

36

Recruited

3,200+

Jazz Pharmaceuticals

Lead 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

Findings from Research

In a study of 47 patients with refractory epilepsy, highly purified cannabidiol (CBD) was found to be effective in reducing seizure frequency, regardless of whether it was used with clobazam (CLB) or not.

Patients taking CBD alongside CLB had a significantly higher responder rate (more than 50% reduction in seizures) at the point of best seizure control within the first year, indicating that combining these treatments may enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. Savage, TE., Sourbron, J., Bruno, PL., et al.[2021]

A study of 54 patients with refractory epilepsy showed that cannabidiol (CBD) maintains its efficacy in reducing seizures over a treatment period of up to 60 months, with a consistent seizure response rate of around 41.7% to 42.6%.

CBD was particularly effective for patients with tuberous sclerosis complex and was generally well tolerated, with drowsiness and diarrhea being the most common side effects, indicating it is a safe option for long-term use as an antiepileptic drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term efficacy of cannabidiol in the treatment of refractory epilepsy. Patel, S., Grinspoon, R., Fleming, B., et al.[2021]

Cannabidiol (CBD) at a dosage of 10 mg/kg/day has been shown to significantly reduce seizure frequency in patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) when used alongside current clinical management, based on data from four randomized controlled trials involving these conditions.

The cost-effectiveness analysis indicated that the incremental cost-effectiveness ratios (ICERs) for CBD treatment were around £31,107 per QALY for LGS and £36,046 per QALY for DS, but these figures were subject to uncertainty due to methodological concerns raised by the Evidence Review Group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol for Adjuvant Treatment of Seizures Associated with Lennox-Gastaut Syndrome and Dravet Syndrome: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Wijnen, B., Armstrong, N., Ramaekers, B., et al.[2021]

Pure, plant-derived cannabidiol (CBD; Epidiolex) has been shown to significantly reduce seizure frequencies in patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) by 17% to 23% compared to placebo, making it an effective adjunctive therapy for treatment-resistant epilepsy.

CBD is generally well tolerated, with common side effects including somnolence, diarrhea, and elevated liver enzymes, and it is the first cannabis-derived medication approved by the FDA for these conditions, providing a new treatment option for patients aged 2 years and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. Chen, JW., Borgelt, LM., Blackmer, AB.[2020]

Epidiolex, a 99% pure oral CBD extract, has been shown to significantly reduce seizure frequency in patients with medically refractory epilepsy, leading to its FDA approval.

The review highlights the safety profile of Epidiolex, noting that while it is effective, understanding its adverse effects is crucial for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects. Sekar, K., Pack, A.[2020]

Epidiolex® (CBD) is effective for treating epilepsy in patients over 2 years old, but it can interact with other medications, as seen in a case where it contributed to lithium toxicity in a patient with Lennox-Gastaut syndrome.

After discontinuing lithium due to toxicity, the patient improved and remained seizure-free on CBD and two other antiseizure medications, highlighting the importance of monitoring drug interactions when adding CBD to treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-Drug Interactions Between Cannabidiol and Lithium. Singh, RK., Dillon, B., Tatum, DA., et al.[2020]

In a study involving 45 children with treatment-resistant epilepsy, cannabidiol (CBD) significantly reduced major seizure frequency by 54-72% and increased seizure-free days by an average of 7.52 days over 36 months, demonstrating its efficacy as an adjunctive treatment.

CBD was well tolerated at doses up to 50 mg/kg/day, although children who increased their dose beyond 25 mg/kg/day initially reported more adverse events; however, the overall rate of adverse events decreased after transitioning to higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. Park, YD., Linder, DF., Pope, J., et al.[2021]

In a study of 108 patients with refractory epilepsy taking Epidiolex®, 75% remained on the treatment at the final evaluation, indicating that it is generally well-tolerated and effective for long-term use.

However, 46.3% of patients experienced treatment-emergent adverse effects, with 14.5% discontinuing due to these effects, highlighting the need for further research on managing side effects and drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy. Georgieva, D., Langley, J., Hartkopf, K., et al.[2023]

In a study of 139 participants with treatment-resistant epilepsy, the use of highly purified cannabidiol (CBD; Epidiolex®) led to significant reductions in adverse events, seizure severity, and seizure frequency over 12 weeks, with improvements sustained for up to 48 weeks.

The study demonstrated that CBD was well-tolerated, with a decrease in adverse events from 40.8 to 33.2 and a reduction in seizure severity scores from 80.7 to 39.2, indicating its efficacy as a treatment option for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study. Szaflarski, JP., Bebin, EM., Cutter, G., et al.[2019]

Cannabidiol (CBD) has been approved for use as an adjunctive therapy for treating epileptic seizures in patients aged 2 years and older with Lennox-Gastaut syndrome and Dravet syndrome, showing its efficacy in reducing seizures when combined with clobazam.

Experts recommend a gradual dose escalation of CBD over 4 weeks to optimize treatment, and advise monitoring for adverse effects, suggesting that treatment should continue for at least 6 months if well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol for the treatment of Lennox-Gastaut syndrome and Dravet syndrome: experts' recommendations for its use in clinical practice in Spain. García-Peñas, JJ., Gil Nagel-Rein, A., Sánchez-Carpintero, R., et al.[2022]

Highly purified cannabidiol (CBD), approved as Epidiolex®, has shown significant efficacy in increasing seizure threshold in wildtype mice, suggesting its potential as an anticonvulsant, particularly through its interaction with the TRPV1 receptor.

The study indicates that while TRPV1 plays a crucial role in CBD's anticonvulsive effects, other mechanisms may also be involved, as evidenced by the partial attenuation of CBD's effects in TRPV1 knockout mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticonvulsive Properties of Cannabidiol in a Model of Generalized Seizure Are Transient Receptor Potential Vanilloid 1 Dependent. Gray, RA., Stott, CG., Jones, NA., et al.[2020]

In a long-term open-label extension trial involving 264 patients with Dravet syndrome, add-on cannabidiol (CBD) treatment resulted in significant reductions in seizure frequency, with a median reduction of 38% to 44% for convulsive seizures and 39% to 51% for total seizures over 48 weeks.

The safety profile of long-term CBD use was acceptable, with 93.2% of patients experiencing adverse events, mostly mild to moderate, and 85% of patients or caregivers reporting an improvement in the patient's overall condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial. Devinsky, O., Nabbout, R., Miller, I., et al.[2020]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

The long-term efficacy of cannabidiol in the treatment of refractory epilepsy. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Cannabidiol for Adjuvant Treatment of Seizures Associated with Lennox-Gastaut Syndrome and Dravet Syndrome: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Drug-Drug Interactions Between Cannabidiol and Lithium. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study. [2019]

10. Spain pubmed.ncbi.nlm.nih.gov

Cannabidiol for the treatment of Lennox-Gastaut syndrome and Dravet syndrome: experts' recommendations for its use in clinical practice in Spain. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Anticonvulsive Properties of Cannabidiol in a Model of Generalized Seizure Are Transient Receptor Potential Vanilloid 1 Dependent. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial. [2020]