Safety, and Tolerability of Epidiolex In Patients ((Ages 1 - 19 Years) With Intractable Epilepsy

The specific goals of this phase I dose finding study conducted in consecutively enrolled
patients 1-18 years of age are to prospectively and longitudinally assess the safety and
tolerability, including cognitive effects, of CBD at various doses between 5 mg/kg/day and 25
mg/kg/day with additional titration in some subjects up to 50 mg/kg/day. In order to
participate in the study, participants will need to fulfill the inclusion and exclusion
criteria.

The goal of the study is to fulfill the mandate of "Carly's Law" and to provide patients with
debilitating epileptic conditions with access to CBD as an add-on treatment. Other care
including routine neurological care that is not related to participation in the CBD study
will need to be provided by patients' primary/current treating neurologist.

Inclusion Criteria:

- Patients between 1 years (12 months)-18 years with drug resistant epilepsy confirmed
by video EEG recording report

- Patient should have history of a trial of at leas four drugs, including one trial of a
combination of two concomitant drugs without successful seizure control. Vagal nerve
stimulation, RNS deep brain stimulation, or the ketogenic diet can be considered
equivalent to a drug trial. Patient suffering from an epileptic syndrome that is known
to be refractory to treatment, such as Dravet or Lernnox Gastaut Syndrome, may be
included after a trial of only two drugs

- Between 1-4 baseline anti-epileptic drugs at stable doses for a minimum of 4 weeks
prior to submitting records for review by the CBD Treatment Approval Committee

- VNS or RBS must be on stable settings for a minimum of 3 months

- If on ketogenic diet, must be on stable ration for a minimum of 3 months

- Review of the following patient medical information:

- Most recent ECG report,

- Video/EEG monitoring report confirming the diagnosis of epilepsy,

- Evidence that the patient has failed 4 AEDs as indicated above,

- Patient must have at least 4 clinically countable seizures per month,

- Seizure history to include a documented history of generalized (drop, atonic, tonic
clonic, and/or myoclonic) seizures, focal seizures without loss of consciousness with
a motor component, focal seizures with loss of consciousness, or focal seizures with
secondary generalization, complex partial seizures with a motor or tonic component,
and I or altered awareness seizures,

- Results of routine testing including blood work (CBC, CMP, LFTs renal panel, Urinary
Analysis, and levels of all AEDs) and digital copy of a routine EEG along with the
formal written report performed within 3 months prior to submitting records for CBD
Treatment Approval review. If applicable, results of any metabolic or genetic testing
performed should be included in submitted records for review! If any AED dose was
adjusted in the preceding 3 months, level on the new dose will need to be provided.

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

- Acceptable method of contraception (or abstinence) for women of childbearing potential
and for male patients with partners of childbearing potential, and female patients
must have_a negative urine pregnancy test on the day ofinitating CBD.

- For patients who agree to participate in the optional neuroimaging sub study, an MRI
screen will be obtained to show that the patient does not have contraindication to
receiving MRI/fMRI at 3 Tesla (e.g., metallic artifact).

- Patients are able to supply investigator with seizure calendars for the past 3 months
prior to submitting records for CBD Treatment Approval Committee review. The patient
will need to provide an updated calendar at the time of enrollment.

- Approval for inclusion by the CBD Treatment Approval Committee.

- Current State of Alabama Resident

- Acceptable documentation of Alabama residency includes the following:

- a state issued ID, such as a driver's license, from patient or patient's parent/
legally authorized representative (LAR).

- documents showing the patient or patient's parent/LAR rents/owns property in the
state,

- state voter registration from patient or patient's parent/LAR, or

- a recent state tax return from patient or patient's parent/LAR.

Exclusion Criteria:

- Active Psychogenic non-epileptic seizures (PNES); Patients with more than 1 year
freedom from PNES will not be excluded,

- Patients who are pregnant, breastfeeding, or not using acceptable methods of
contraception during the course of the study and for three months thereafter,

- Male patient's partner is of child bearing 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

- History of substance abuse/addiction,

- Use of medical marijuana or CBD based product in the past 30 days,

- Initiation offelbamate within last 12 months,

- Allergy to CBD or any marijuana-type products,

- ALT >5 x ULN or AST >5 x ULN, as seen in participant's laboratory results submitted to
the CBD Treatment Approval Committee for review.

- Hemoglobin <1 0 or Hematocrit <30 or WBC < 2000, as seen in participant's laboratory
results submitted to the CBD Treatment Approval Committee for review.

- In Investigator's judgement, active medical condition/treatment that impacts study
activities.

- Unable to provide consent (and no LAR),

- Unable/Failure to comply with study visits/requirements and/or instructions.

- Confirmed diagnosis for Dravet Syndrome or Lennox Gastaut Syndrome that qualifies the
patient for a GW Dravet Syndrome or LelUlox Gastaut Syndrome randomized controlled
clinical trial for which the patient is eligible pursuant to the GW clinical trial
enrollment criteria unless

- (a) there is no study that is either actively open for enrollment of patients at UAB
or that is expected to actively begin enrolling patients at The University of Alabama
at Birmingham within two (2) months of the date on which the patient is screened for
the UAB Pediatric CBD Program or UAB Adult CBD Program.Primary residence in a State
different than Alabama.

- Subjects with contraindications to MRI!fMRI at 3 Tesla (e.g., metallic artifact) will
not be offered participation in the optional substudy.