Company decision

This prospective double blind phase II study seeks to evaluate the safety and efficacy of BRC-003, a high CBD investigational product, in the treatment of refractory PTE (Post-Traumatic Epilepsy). The research is divided into two phases: an open-label dose-finding phase (Part A) and a subsequent randomized controlled phase (Part B). This design aims to provide a thorough understanding of the investigational product's impact on seizure frequency, seizure severity, mood, anxiety, sleep, and quality of life.

Post-traumatic epilepsy (PTE) is a debilitating disorder characterized by recurrent seizures that develop following traumatic brain injury (TBI). Approximately 30 to 50% of patients with PTE may develop refractory epilepsy, wherein seizures persist despite treatment with multiple antiseizure medications (ASMs) or other therapeutic intervention. Moreover, the debilitating side effects of some ASMs can impact treatment compliance and patient quality of life; the side effects of ASMs may be more severe in patients with PTE.

Cannabis sativa L. has an extensive history of medical and therapeutic use. Growing interest in the utility of cannabinoids for medical indications including epilepsy, pain, nausea, appetite stimulation, muscle spasticity, and psychological disorders has led to its legalization in at least 14 countries as well as the regulatory approval of cannabis extract preparations, synthetic cannabinoids, and analogues. Cannabidiol (CBD), a non-intoxicating cannabinoid, has shown significant anticonvulsant properties and has received FDA (Food and Drug Administration) approval in three refractory seizure disorders.

This prospective study seeks to evaluate the safety and efficacy of BRC-003, a high CBD investigational product, in the treatment of refractory PTE. The research is divided into two phases: an open-label dose-finding phase (Part A) and a subsequent randomized controlled phase (Part B). This design aims to provide a thorough understanding of the investigational product's impact on seizure frequency, seizure severity, mood, anxiety, sleep, and quality of life.

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for enrollment into the study:

1. Diagnosis consistent with PTE,

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2. History of a trial of at least two AEDs, including one trial of a combination of two concomitant AEDs, without successful seizure control. Vagus nerve stimulation (VNS), RNS, deep brain stimulation (DBS), or the ketogenic diet can be considered an equivalent to a drug trial,

3. Between 1-4 baseline anti-epileptic drugs at stable doses for a minimum of 4 weeks prior to enrollment,

4. VNS, DBS, or RNS must be on stable settings for a minimum of 3 months,

5. If on ketogenic diet, must be on stable ratio for a minimum of 3 months.

6. If applicable, documentation (including date of surgery) of prior VNS, DBS, RNS, Corpus Callosotomy, or other epilepsy surgery the patient has received.

7. Age 18 years and older

8. Acceptable method of contraception (or abstinence) for women of childbearing potential and for male patients with partners of childbearing potential; female patients must have a negative urine pregnancy test on the day of initiating IMP.

9. Weight ≥ 40 kg

Exclusion Criteria:

• Participants meeting any of the following criteria will not be eligible for participation in the study:

  1. Active psychogenic non-epileptic seizures (PNES),
  2. Patients who are pregnant, breastfeeding, or not using acceptable methods of contraception during the course of the study and for three months thereafter,
  3. Male patient's partner is of childbearing potential; unless willing to ensure that they (male patients) or their partner(s) are using acceptable methods of contraception during the course of the study and for three months thereafter,
  4. Use of medical marijuana, cannabis, hemp, or CBD based product in the previous 30 days, or during the study.
  5. Weight ≤ 40 kg
  6. Initiation of felbamate within the last 12 months,
  7. Allergy to CBD or any cannabis-type products,
  8. ALT >5 × ULN or AST >5 × ULN, as seen in participant's laboratory results,
  9. Hemoglobin <10 or hematocrit <30 or WBC < 2000, as seen in participant's laboratory results,
  10. Current (as assessed via C-SSRS) or history of suicidal ideation or attempt,
  11. In PI's judgment, active medical condition/treatment that impacts study activities,
  12. Unable to provide consent,
  13. No access to a mobile phone, and internet, not willing or able to download the eDiary application,
  14. Inability or failure to comply with study visits, requirements and/or instructions, and
  15. For Part B, prior enrollment in Part A of the study