What side effects are associated with this type of intervention?

Common treatments for Tuberous Sclerosis Complex (TSC) that are similar to Cannabidiol (CBD) include those that modulate the endocannabinoid system. Known side effects of CBD include drowsiness, decreased appetite, diarrhea, fatigue, and elevated liver enzymes. These side effects are typically mild to moderate. Other treatments for TSC, such as antiepileptic drugs, may cause dizziness, weight gain, and behavioral changes. Patients should discuss these potential side effects with their healthcare provider to ensure proper management.

What prior FDA approvals exist?

The FDA has approved several treatments for Tuberous Sclerosis Complex (TSC), primarily focusing on managing seizures and other symptoms associated with the condition. One notable approval is for Everolimus, an mTOR inhibitor, which helps reduce the size of brain and kidney tumors in TSC patients. While specific FDA approvals for drugs that modulate the endocannabinoid system, like Cannabidiol (GWP42003-P), are limited, Cannabidiol itself has shown promise in clinical trials for its anti-inflammatory and neuroprotective effects, particularly in managing seizures in TSC, Dravet Syndrome, and Lennox-Gastaut Syndrome.

What other types of research exist?

Promising novel alternatives to GWP42003-P for Tuberous Sclerosis Complex patients include: 1) Everolimus, an mTOR inhibitor that has shown efficacy in reducing seizure frequency and improving other TSC-related symptoms. 2) Fenfluramine, which has been effective in reducing seizures in Dravet syndrome and may have potential benefits for TSC patients. 3) The ketogenic diet, which has been beneficial in managing refractory epilepsy and could be considered for TSC-related seizures. These alternatives should be discussed with a healthcare provider to determine the best individualized treatment plan.

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Cannabidiol for Seizures

Phase 3

Recruiting

Research Sponsored by GW Research Ltd

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants who have uncontrolled seizures, and who are currently receiving 1 or more antiseizure medication (ASMs)

Participants with TSC must have a diagnosis per the 2012 International Tuberous Sclerosis Complex Consensus Conference

Must not have

Has significantly impaired hepatic function prior to Visit 3

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at day 1 (visit 3), day 169 (visit 13), and day 365 (eot)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects of GWP42003-P may include sleepiness, decreased appetite, diarrhea, fever, vomiting and fatigue. Since it contains cannabidiol derived from cannabis plants there might also be risks related to mood changes or allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I have been diagnosed with Tuberous Sclerosis Complex according to the 2012 guidelines.

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My seizures are not fully controlled by my current medication.

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My child is between 1 month and 2 years old and has TSC, DS, or LGS.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My liver is not working well.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at day 1 (visit 3), day 169 (visit 13), and day 365 (eot)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at day 1 (visit 3), day 169 (visit 13), and day 365 (eot)

This trial's timeline: 3 weeks for screening, Varies for treatment, and at day 1 (visit 3), day 169 (visit 13), and day 365 (eot) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Clinician Global Impression of Change/Severity (CGIC/S) Score

Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score

Secondary study objectives

Number of Treatment Responders

Percentage Change from Baseline in Total Countable Seizures

Side effects data

From 2016 Phase 3 trial • 225 Patients • NCT02224560

30%

Somnolence

26%

Decreased appetite

15%

Diarrhoea

12%

Upper respiratory tract infection

12%

Vomiting

11%

Pyrexia

11%

Nasopharyngitis

10%

Fatigue

Headache

Convulsion

Lethargy

Status epilepticus

Insomnia

Irritability

Pneumonia

Lymphopenia

Constipation

Pneumatosis intestinalis

Adenovirus infection

Pneumonia mycoplasmal

Respiratory syncytial virus infection

Delayed recovery from anaesthesia

Aspartate aminotransferase increased

Alanine aminotransferase increased

Gamma-glutamyltransferase increased

Pleural effusion

Device malfunction

Hypotension

100%

80%

60%

40%

20%

Study treatment Arm

GWP42003-P 20 mg/kg/Day Dose-Safety Analysis Set

Placebo-Safety Analysis Set

GWP42003-P 10 mg/kg/Day Dose-Safety Analysis Set

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

1Treatment groups

Experimental Treatment

Group I: GWP42003-PExperimental Treatment1 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.).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

GWP42003-P

2016

Completed Phase 3

~1740

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Tuberous Sclerosis Complex (TSC) often involve modulation of the endocannabinoid system, anti-inflammatory properties, and potential neuroprotective effects, as seen with Cannabidiol (CBD). CBD modulates the endocannabinoid system, which helps regulate pain, mood, and memory, and has anti-inflammatory properties that reduce neuroinflammation. Additionally, its neuroprotective effects may protect against neuronal damage and improve brain function. These mechanisms are crucial for TSC patients who experience seizures and other neurological symptoms, offering a comprehensive approach to symptom management.

Impact of Endocannabinoid System Manipulation on Neurodevelopmental Processes Relevant to Schizophrenia.Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway.Hippocampal mammalian target of rapamycin is implicated in stress-coping behavior induced by cannabidiol in the forced swim test.