CASCADE: CAnnabidiol Study in Children With Autism Spectrum DisordEr

CAnnabidiol Study in Children With Autism Spectrum DisordEr (CASCADE): A Double-Blind, Placebo-Controlled Study to Investigate Efficacy and Safety of Cannabidiol in Children and Adolescents With Autism

This is a randomized, placebo-controlled study but all study participants will receive the active study medication at some point during the study for at least 12 weeks, and some children with receive CBD for the entire study.

Autism spectrum disorder (ASD) is a relatively common neurodevelopmental disorder manifest by social communication deficits and restricted and repetitive interests. Individuals with ASD often have behavioral issues and psychiatric comorbidities which can be very hard to manage. Currently, there are only two FDA approved medications (aripiprazole and risperidone) for the treatment of irritability in ASD. Both medications have the potential for side effects and are not tolerated in all children with ASD. Anecdotal and some preliminary studies suggest that cannabidiol (CBD), a non-psychoactive cannabinoid in the marijuana plant, may lead to improvements in symptoms of ASD including irritability, aggressive behaviors, and anxiety.

In this study the investigators will test whether CBD leads to differences in behaviors commonly associated with ASD. The main behavioral problems investigators will study are irritability and aggressive behavior. This study will also measure changes in other behaviors seen in ASD such as anxiety, social interaction difficulties, repetitive behaviors, attentional problems, hyperactivity, repetitive behaviors, and quality of life. Study investigators will also test whether there are any important side effects of CBD in children and adolescents with ASD.

Inclusion Criteria:

• Male or female children and adolescents aged 5-17 years, inclusive, at the time of screening.
• Judged by the investigator to be in good health at screening based upon the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results.
• Patients must have a previous documented diagnosis of ASD by a medical or psychological professional.
• Patients must be assessed by the Investigator as being moderately to severely impacted due to ASD
• Patients who are taking psychotropic medication(s) should be on a stable regimen of no more than 2 medications for at least 4 weeks preceding study Screening and must maintain that regimen throughout the study. Psychotropic medications include (but are not limited to) antipsychotics, antidepressants, mood stabilizers, anxiolytics, and ADHD medications.
• Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of one or two AEDs, or must be seizure-free for 1 year if not currently receiving AEDs.
• Patients with seizures should be on a stable regimen for the 3 months preceding study enrollment of no more than 2 of the permitted anti-epileptic drugs (AEDs). Patients must remain on a stable AED dose throughout the study.
• If patients are receiving non-pharmacological educational, behavioral, and/or dietary interventions or therapies, they must be stable and have been doing so for 2 months prior to screening. Changes with school breaks are expected and do not apply.
• Patients must have a BMI of between 12-32 kg/m2 (inclusive).
• Females of childbearing potential and must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at all designated visits.
• Patients/caregivers agree to abide by all study restrictions and comply with all study procedures.
• Parents/caregivers must be able to read and respond to questions and questionnaires in English.
• Patients/caregivers must be adequately informed of the nature and risks of the study and give written informed consent prior to screening.
• Parents/caregiver(s) must provide written consent to assist in study drug administration.
• In the Investigator's opinion, patients/caregivers are reliable and willing and able to comply with all protocol requirements and procedures (including scheduled visits and confinement periods).

Exclusion Criteria:

• Adolescent females who are pregnant, nursing, or planning a pregnancy. Females of childbearing potential and male patients with a partner of childbearing potential who are unwilling or unable to use standard acceptable methods of contraception (including abstinence, hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, or intrauterine device) for the duration of the study and for 1 month after the last dose of study medication.
• History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to CBD (Epidiolex) or its ingredients.
• Exposure to any investigational drug or device < 30 days prior to screening, or plans to take another investigational drug at any time during the study.
• Use of any THC or CBD-containing product within 4 weeks of Screening Visit, planned use during the study, or positive THC urine test at screening.
• Patient is using the following medications: clobazam (Onfi, Frisium), felbamate (Felbatol), vigabatrin (Sabril), or everolimus (Afinitor).
• Plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
• Patient has ALT, AST, total bilirubin, or creatinine levels ≥ 2 times the ULN, alkaline phosphatase levels ≥ 3 times the ULN, or Hct <1.2 times the LLN as determined from screening safety laboratories.
• Severe or unstable symptoms of ASD that may interfere with the study outcome evaluations and interpretation of results.
• Suffering from acute or progressive neurological disease, psychosis, schizophrenia or any psychiatric disorder or severe psychiatric abnormalities that are likely to require changes in drug therapy or interfere with the objectives of the study or the ability to adhere to protocol requirements.
• Has suspected or confirmed cardiovascular disease.
• History of treatment for, or evidence of, drug or alcohol abuse within the past year.