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

Study Overview
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Brief Summary
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To evaluate the safety, tolerability and efficacy of oral administration of PTL101 (cannabidiol) for the treatment for pediatric intractable epilepsy. Study will include a 4-week observation period ,12 weeks of treatment and 2 weeks of follow up.

Detailed Description
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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.

Official Title
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A Phase II, Open-label, Single-center Clinical Study to Evaluate the Safety, Tolerability and Efficacy of Oral Administration of PTL101 (Cannabidiol) as an Adjunctive Treatment for Pediatric Intractable Epilepsy

Conditions
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Epilepsy Intractable

Intervention / Treatment
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* Drug: PLT101


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLT101<br>PTL101 capsules (50 or 100 mg CBD per capsule) up to 25 mg/kg/day or up to 450 mg/day, the lower of the two. Twice daily (morning and evening). | Drug: PLT101<br>* PTL 101 (Cannabidiol, CBD) Two piece hard capsules filled with seamless gelatin matrix green beads containing CBD (50 or 100 mg CBD per capsule) The beads should be administered following a meal, mixed with food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of study treatment related adverse events (AEs) |  | 12 weeks of treatment + 2 weeks follow up | 
| Percent change in mean countable monthly seizure frequency |  | 12 week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of all adverse events (AEs) |  | 12 weeks of treatment + 2 weeks follow up | 
| assessment of Caregiver Global Impression of Improvement using a 5-point rating scale |  | after 5 weeks of maintenance dose and at end of treatment | 
| assessment of Caregiver Global Impression of Seizure Severity using a 5-point rating scale |  | after 5 weeks of maintenance dose and at end of treatment |