Abstracts

Rationale: The State of Georgia desired to provide patients with Treatment Resistant Epilepsy (TRE) access to CBD, to contribute to scientific literature on CBD, and evaluate CBD as an adjunctive antiepileptic drug (AED) treatment in reducing Seizure Frequency (SZF). Methods: A multi-center study for TRE patients, 1-18 years at consent, with an 8 week baseline (B/L), titration (V2), and CBD treatment up to a 25 mg/kg/day for at least 27 weeks (V6), were included for analysis. The SZF were recorded in a web-based diary. Statistical analysis consisted of a comparison of median B/L SZF to SZF while receiving CBD, a generalized linear model to evaluate the effect of etiological and demographic factors on major SZF, and a test of randomness to determine if major seizure-free days (SZ-FD) were due to treatment effect. Results: As of 4/30/2016, 30 patients (average age 10.7 years, R=2-19 years, male (n=20)), completed V6. Common causes of epilepsy were cryptogenic (n=14; 47%), cortical dysplasia (n=9; 30%); 7 patients had a history of epilepsy surgery. Average number of AEDs was 4 (R=2-8); 19 (63%) received Clobazam. Major seizures (complex partial with motor involvement, tonic, atonic, and generalized (including secondarily) tonic clonic), when compared to B/L ranged from a median reduction of 37.7%-88.5% (V2-V6). At V6, 20% of patients reported an increase in major SZF (R=14.2%-200%) and 24 (80%) patients reported an overall reduction in major SZF (R=7.9%-100%). Six patients (20%) reported 100% of SZ-FD at V6. Overall there was an increase in total SZ-FD for all patients for V2-V6 when compared to B/L. The test for randomness of major SZ-FD indicated that major SZ-FD may be due to treatment effect in some patients. The generalized linear model with major SZF as the outcome variable predictor show that cryptogenic is a significant etiological factor in reducing the number of major seizures (p-value= 0.0372). There was no significant effect on major SZF due to sex, age, number of AEDs, other etiologies, Clobazam use, or VNS. Adverse events were reported in 27 patients (90%) included URI (n=48), GI (n=46), infection (n=32), febrile (n=13), somnolence (n=8), increase SZF (n=6), rash (n=4), allergy (n=1), and other (n=18). Seven patients reported mild to severe Serious Adverse Events (SAE) and included respiratory/pneumonia (n=7), increased SZF (n=4), GI (n=1), and burn (n=1); none of the SAE were CBD related. Three patients withdrew primarily due to lack of efficacy before reaching V6; thus were not included in analysis. Conclusions: This study supports the use of CBD as a treatment for children with TRE, showing a decrease in major SZF and increase in SZ-FD compared to B/L. In this patient sample, cryptogenic etiology was the only significant predictor of efficacy. Specific study limitations include open label, mixed indications, and a small sample size. Treatment has been well-tolerated in doses up to 25 mg/kg/day, with no CBD related SAE. Funding: State of Georgia Investigational Drug supplied by GW Pharma