| Eligibility |
Inclusion Criteria:
- Men and women aged 2 years to 18 years.
- Diagnosis of treatment-resistant epilepsy according to the criteria of the
International League Against Epilepsy (ILAE) (Kwan et al., 2010).
- Participants with at least 4 epileptic seizures with intervals no longer than 21 days.
- In treatment with up to 3 AEDs concomitantly and at stable doses for at least 1 month
before the baseline assessment and expected to remain stable during the period of the
trial. Vagus nerve stimulation (VNS) will be considered as an AED.
- Availability of a legal guardian able to follow the protocol (e.g., understand and
fill up diaries) and visitation and medication schemes, according to the decision of
the investigator.
- Availability of brain neuroimaging exams (magnetic resonance or computed tomography)
collected within the last 5 years.
- No significant comorbid conditions, according to medical decision, to other criteria
in this Protocol, and to additional assessments: medical records, blood pressure,
heart rate, and temperature measures, physical exam, ECG, EEG, and laboratory tests.
- Women in reproductive age may be included as long as they are sexually abstinent or
using effective contraceptive methods.
- Participants and their legal guardians, when applicable, must sign an informed consent
form approved by the local ethics committee.
Exclusion Criteria:
- Occurrence of simple partial seizures (preserved consciousness) only, with no motor
symptomatology.
- History or presence of pseudoseizures.
- History of suicide attempt.
- History of major depression.
- Pregnancy.
- Drug use.
- Hypertension.
- Participants with severe dysphagia and no gastric or nasogastric tubes.
- Current treatment with drugs that may significantly affect the metabolism of CBD,
except AEDs if stable for at least 1 month before the screening interview.
- Presence of any clinical or neuroimaging finding suggestive of brain disorders, brain
tumors, or metabolic or neurodegenerative diseases of rapid progression.
- Presence of acute and clinically significant diseases as assessed by a medical
investigator, such as kidney, liver, urinary, bowel, or respiratory infections.
- Presence of known chronic and clinically significant diseases as assessed by a medical
investigator and which may interfere with participation in the trial or pose safety
risks for the participant.
- History of liver, kidney, lung, hematological, heart, or psychiatric diseases that may
affect the volunteers' health or participation in the trial.
- Hypotension or hypertension with any etiology and requiring pharmacological
management.
- History of surgeries that may affect the volunteers' health and/or participation in
the trial.
- Regular or intermittent use of marijuana over the 60 days preceding the baseline
assessment.
- Regular or intermittent treatment with CBD over the 60 days preceding the baseline
assessment.
- History of allergies or idiosyncratic reactions to Cannabis sativa derivatives or
components of the pharmaceutical formulation.
- Clinically significant ECG alterations as judged by a medical investigator.
- Participation in other clinical trials within less than 3 months before the baseline
assessment.
- Donation or loss of 450 mL or more of blood within 90 days before the baseline
assessment.
- Impaired liver function: AST, ALP, alkaline phosphatase and ?GT values more than 3
times above the upper limit of the reference value. Results of ?GT values 3 times
above the upper limit will only be accepted if attributable to liver enzymatic
induction caused by concomitant treatment with AEDs and with levels of other liver
enzymes lower than 3 times the upper limit of the reference range.
- Participants with clinically significant discrepancies from the reference ranges of
the following laboratory tests: creatinine clearance < 50 ml/min, platelets <
100.000/µL, and neutrophils < 1.800/µL.
|
