Cannabidiol for Seizures

No longer recruiting at 12 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: GW Research Ltd

Must be taking: Antiseizure medications

Disqualifiers: Tumor growth, Cardiovascular conditions, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called GWP42003-P (also known as Cannabidiol or CBD) to determine its safety and effectiveness in reducing seizures in young children with conditions like tuberous sclerosis complex, Lennox-Gastaut syndrome, or Dravet syndrome. The trial aims to assess the treatment's efficacy and how the body processes it. Children under two years with uncontrolled seizures, despite taking one or more seizure medications, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for seizure management.

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have uncontrolled seizures despite being on one or more antiseizure medications, suggesting you may continue your current treatment.

Is there any evidence suggesting that GWP42003-P is likely to be safe for humans?

Studies have shown that GWP42003-P, also known as cannabidiol, is generally well-tolerated by people with seizures. Research indicates that long-term use can consistently reduce seizures, with many patients or their caregivers reporting overall improvement. A review of studies found that cannabidiol can cause side effects, but these are mostly mild to moderate. The FDA has approved this treatment for certain types of epilepsy, supporting its safety. However, like all medications, it can affect people differently, and some might experience varying effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for seizures?

Researchers are excited about GWP42003-P for seizures because it harnesses cannabidiol, a compound derived from cannabis, which offers a unique mechanism of action compared to traditional anti-seizure medications. Unlike standard treatments like valproic acid or lamotrigine that primarily target electrical activity in the brain, cannabidiol interacts with the endocannabinoid system, potentially offering a new pathway for managing seizures. This treatment also offers flexible dosing options, allowing personalized adjustments to maximize efficacy and minimize side effects. Such versatility and novel action have the potential to provide new hope, especially for patients with treatment-resistant epilepsy.

What evidence suggests that GWP42003-P might be an effective treatment for seizures?

Research has shown that GWP42003-P, also known as cannabidiol, may help reduce seizures in conditions like Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). In this trial, participants will receive GWP42003-P, which studies have shown to significantly reduce drop seizures in people with LGS. Long-term use of cannabidiol has been well-tolerated and continued to reduce seizures over 48 weeks. Most participants and their caregivers noticed overall improvements. This suggests that GWP42003-P could be an effective option for managing seizures in these conditions. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive adjunctive GWP42003-P with a 2-week titration period followed by flexible dose optimization for up to 52 weeks

52 weeks

Visits at Day 1, Day 169, and Day 365

Taper

Participants undergo a 10-day taper period to safely reduce medication dosage

10 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GWP42003-P

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.

How Is the Trial Designed?

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

Jazz Pharmaceuticals Research UK Limited

Industry Sponsor

Trials

1

Recruited

150+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

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) 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 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]

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This systematic review and meta-analysis investigates the frequency and risk of developing adverse events from cannabidiol use in patients ...