Abstracts

Rationale: Pharmaceutical formulation of CBD (Epidiolex, GW Research Ltd) has been demonstrated to reduce both seizure frequency and severity in patients with refractory epilepsy suggesting potential as an anti-epileptic drug (AED). In addition, a drug interaction with clobazam leading to increased levels of its active metabolite, N-desmethylclobazam, has been reported. This study investigates if there is a relationship between the presence of concomitant clobazam and improvement in seizure frequency and severity in patients enrolled in the State of Alabama funded open label expanded access CBD program. Methods: A total of 132 subjects were in the initial dataset. 114 of the 132 patients had an eligible 12±2 weeks follow-up visit. 46 (24 adults /21 children, 14 on clobazam/ 32 not on clobazam) of the 114 patients had a CBD dose at 10 and 25 mg/kg/day dose at the defined follow-up interval and were eligible for this particular analysis. All participants had treatment refractory epilepsy, defined as failing = 4 AEDs, including a trial of 2 concomitant AEDs. AEDs must be at stable dose 1 month prior to study enrollment. CBD dosing was weight based and could be increased every 2 weeks by 5 mg/kg/day to a maximum dose of 50 mg/kg/day depending on tolerance and seizure control. Other AEDs could be adjusted once CBD was started. Due to the known interaction with clobazam, investigators frequently decreased the clobazam dose if a participant reported sedation and had an elevated clobazam/N-desmethylclobazam level. Seizure counts and Chalfont Seizure Severity Scale (CSSS) were obtained at every clinic visit. Using independent measures t-test and a multiple linear regression model, change in absolute total seizure frequency, percent change in seizure frequency, change in total CSSS score, and percent change in total CSSS score from baseline (off CBD) to 12 ± 2 week follow up at a CBD dose of 10 mg/kg/day and 25 mg/kg/day were analyzed. These measures were analyzed in both patients taking clobazam (clobazam group) and CBD and patients taking CBD and other AEDs (no clobazam group). Results: No significant difference in percent changes in neither seizure frequency reduction nor total CSSS score from baseline, and no change in absolute seizure frequency from baseline to 10 mg/kg/day and 25 mg/kg/day of CBD were noted between the clobazam and no clobazam groups in both t-test and regression models. The regression model did reveal a significant change in percent reduction in CSSS score in all patients (p=0.03); however, the t-test did not show significant difference, and both models within individual adult and pediatric arms did not reveal a significant difference between the clobazam and no clobazam groups. Conclusions: This analysis suggests that CBD’s positive effects in reducing seizure frequency and severity are not dependent on the presence of concomitant clobazam and the known interaction of CBD increasing serum clobazam/desmethylclobazam levels. This needs to be confirmed with studies in more controlled conditions. Funding: The UAB CBD Program is funded by the State of Alabama Department of Commerce through "Carly's Law".