A Study to Evaluate the Safety, Tolerability and Efficacy of Oral Administration of PTL101 (Cannabidiol) as an Adjunctive Treatment for Pediatric Intractable Epilepsy

This is an open-label, single-center study recruiting approximately 15 male or female pediatric (ages 2-15, inclusive) patients with, intractable epilepsy, on stable doses of antiepileptic drugs (AEDs). The study comprised of the following period: 4 weeks observation period, followed by a 2-week dose titration period, 10-week maintenance treatment period, and a 2-week follow-up of which 1 week is a tapering-off period. Seizures will be recorded by the legal guardian/caregiver in seizure diaries throughout the first 16 weeks of the study.

Inclusion criteria

• Pediatric subjects with refractory epilepsy
• 2-15 years old (inclusive), male or female
• History of the any of the following seizure types: tonic, clonic, tonic-clonic in the form of partial seizures, partial seizures secondarily generalized or primary generalized, complex partial seizures and drop attacks (tonic/atonic).
• At least four clinically countable seizures within 4 weeks of study entry [tonic, clonic, tonic-clonic in the form of partial seizures, partial seizures secondarily generalized or primary generalized and/or complex partial seizures and drop attacks (tonic/atonic)]
• Subject on a stable regimen of 1-4 concomitant antiepileptic drugs (AEDs) for a minimum of 4 weeks prior to enrollment
• History of treatment with at least four AEDs, including one trial of a combination of two concomitant drugs, without successful seizure control
• Subjects with vagal nerve stimulation system must be on stable settings for a minimum of 6 months prior to enrollment
• For subjects undergoing dietary treatment (e.g., ketogenic or modified Atkins diet):

the fat to carbohydrate ratio must be stable for a minimum of eight weeks prior to enrollment

• The subject's legal guardian voluntarily provides consent for participation in the study and signs an Informed Consent Form
• Completed seizures diary for four weeks (±3 days) prior to initiation of the dose titration period (visit 2). Subject will be considered a screen failure if seizures diary was not appropriately completed.

Exclusion criteria

• The subject is currently using or has used cannabis-based or synthetic cannabinoid within three months of study entry
• Subject is unwilling to abstain from use of cannabis-based or synthetic cannabinoid throughout the study period
• Neurodegenerative or deteriorated neurological disease
• History of heart failure
• Known family history (first-degree) of psychiatric disorders
• Psychosis or past psychotic event and/or anxiety disorder
• Current or history of drug abuse/addiction
• Renal, hepatic (ALT/AST >2x upper limit of normal (ULN), bilirubin >2x ULN), pancreatic dysfunctions or laboratory test abnormalities, at the investigator's discretion
• Clinically significant finding in baseline ECG
• Initiation of felbamate treatment within 9 months of screening
• Allergy to CBD or any cannabinoid and/or formulation excipients
• Subject is pregnant, lactating, or planning a pregnancy during the course of the study or within 3 months of study completion
• Subject and legal guardian/caregiver unable to comply with study visits/requirements
• Subject is currently enrolled in, or has not yet completed a period of at least 60 days since ending another investigational device or drug trial(s)