Cannabidiol Oral Solution in Pediatric Participants With Treatment-Resistant Childhood Absence Seizures
Condition: Childhood Absence Epilepsy
MeSH terms: Seizures; Epilepsy, Absence
Intervention: Cannabidiol Oral Solution
Intervention description: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
Intervention MeSH terms: Cannabidiol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 3 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study is to assess the efficacy of Cannabidiol Oral Solution in
      the treatment of pediatric participants with treatment-resistant childhood absence seizures.
      This study will also assess safety, tolerability and pharmacokinetics of Cannabidiol Oral
      Solution, and any improvement in qualitative assessments of participant status over the
      duration of the study in pediatric participants with treatment-resistant childhood absence
      seizures. The study will include a 4-week Screening Period, a 5 or 10 day Titration Period
      (depending study Cohort), a 4-week Treatment Period followed by 5-day Tapering for doses >20
      mg/kg/day and a 4-week Follow-up Period.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient and/or parent(s)/caregiver(s) fully comprehend the informed consent form and
             assent form, understand all study procedures, and can communicate satisfactorily with
             the investigator and study coordinator, in accordance with applicable laws,
             regulations, and local requirements.

          2. Male or female between 3 and 12 years (inclusive) at the time of onset and between 3
             and 17 years of age (inclusive) at the time of consent.

          3. Body weight ≥ 10 kg.

          4. Diagnosed with childhood absence epilepsy, confirmed by electroencephalogram (EEG)
             with at least 3 bursts of general spike wave of 2.7 to 5 hertz lasting ≥3 seconds
             during the 4-hour EEG, and has had an adequate trial of at least 2 antiepileptic drugs
             (AEDs) and are treatment-resistant to at least one AED.

          5. Willingness to not start a ketogenic diet during the Baseline or Treatment Period.

          6. A female patient is eligible to participate in the study if she is premenarchal, or of
             childbearing potential with a negative urine pregnancy test at the Screening Visit. If
             sexually active, she must agree to either complete abstinence from intercourse or use
             acceptable methods of contraception throughout the study and for 4 weeks after
             completion of study participation or discontinuation from investigational product.

          7. A sexually active male patient must be willing to use acceptable methods of
             contraception throughout the study and for 4 weeks after completion of study
             participation or discontinuation from investigational product.

          8. In the opinion of the investigator, the parent(s)/caregiver(s) is willing and able to
             comply with the study procedures and visit schedules and the Follow-up Visits.

          9. General good health based on physical and neurological examinations, medical history,
             and clinical laboratory values completed during the Screening Visit that would
             prohibit the patient from safely participating in the trial as judged by the
             investigator.

        Exclusion Criteria:

          1. Patient or parent(s)/caregiver(s) have daily commitments during the study duration
             that would interfere with attending all study visits.

          2. Has a history of nonfebrile seizures other than absence seizures.

          3. Has a history of febrile seizures after 3 years of age.

          4. Has a history consistent with juvenile absence epilepsy or juvenile myoclonic
             epilepsy.

          5. Currently taking felbamate.

          6. Currently taking phenytoin, fluvoxamine, carbamazepine, or St. John's Wort.

          7. Currently taking concomitant medications that are strong inhibitors/inducers/sensitive
             substrates with a narrow therapeutic index for cytochrome P450 3A4 (CYP3A4), CYP2C9,
             or CYP2C19. (Stable doses of Valproic Acid during the screening, titration, treatment,
             and follow-up periods are permitted).

          8. Currently on a ketogenic diet.

          9. In the opinion of the investigator, any clinically significant, unstable medical
             abnormality, chronic disease, or a history of a clinically significant abnormality of
             the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems.

         10. Clinically significant abnormal liver function test (LFT) values, including albumin,
             direct bilirubin, total bilirubin, aspartate aminotransferase (AST), and alanine
             aminotransferase (ALT) ≥3 times the upper limit of normal (ULN).

         11. History or presence of abnormal electrocardiograms (ECGs) that are clinically
             significant in the opinion of the investigator.

         12. Has a current or history of clinically significant intellectual disability or major
             psychiatric disease, including autism spectrum disorder, which would interfere with
             compliance.

         13. For patients aged 7 to 17 years of age and for whom the Columbia Suicide Severity
             Rating Scale (C-SSRS) is developmentally appropriate, an affirmative answer to queries
             regarding active suicidal ideation with some intent to act but without a specific plan
             or active suicidal ideation with a specific plan and intent on the C-SSRS assessment
             at the Screening Visit.

         14. Any history of attempted suicide.

         15. Previously received any investigational drug or device or investigational therapy
             within 30 days before Screening.

         16. Taken any cannabinoids in the 30 days prior to the Screening Visit.

         17. History of an allergic reaction or a known or suspected sensitivity to any substance
             that is contained in the investigational product formulation.

         18. Known infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).

         19. In the opinion of the investigator, the patient is unsuitable in any other way to
             participate in this study.

         20. Body weight <10 kg or >90 kg.