Abstracts

Rationale: We report preliminary observations of efficacy and tolerability in 25 patients, age 1 to 18 years, enrolled in an expanded access, observational study of CBD (Epidiolex) for treatment of drug resistant epilepsy in Idaho. To qualify for entry patients had to have tried at least 4 previous anti-epileptic medications (AEDs), including at least 1 combination therapy, without adequate seizure control. VNS, RNS, or ketogenic diet were considered equivalent to a therapeutic trial. Patients with confirmed diagnosis of a syndromic epilepsy, such as Dravet syndrome or Lennox-Gastaut syndrome, were allowed if otherwise excluded from participation in ongoing phase 3 trials of CBD. All patients entered study on 1-4 background AEDs. A total of 14 patients had background AED regimens that included clobazam, 6 of whom were also on valproate. One patient was taking valproate without clobazam. Initial CBD dose of 5 mg/kg/day was given orally in 2 divided doses and titrated by 5 mg/kg/day no more frequently than every 7 days, as tolerated, up to maximum dose of 25 mg/kg/day. Methods: There was one screen failure who was not able to tolerate lab draws. The remaining 24 patients have continued in the program for at least 4 months. Subjective seizure assessments are being collected based on caregiver assessments, documented daily in seizure logs with data entered weekly and totalled at each visit. Subjective improvement in seizure frequency has been reported in 20, subjective decrease in seizure duration in 2 (of whom one had similar frequency and one had increased frequency), and no change in seizures in 3, with ongoing dose adjustments. Results: Treatment emergent adverse events (AEs) to date have been reported by 11 patients. These have included lethargy or sedation, reported in 7 patients (21.2%), 5 of whom were on clobazam and valproate in combination when CBD was added. All 7 patients had improved tolerability with adjustment of dosing of background agents. Increased aggression was reported in 3 (12.5%) and diarrhea was reported in 3 (12.5%). To date, all AEs have been responsive to dose adjustments of background AEDs, including 7 patients with clobazam reduction and 3 with valproate reduction. No reduction of CBD has been made. Conclusions: This is an open-label, expanded access program. Subjective reports of improvement in seizures must be interpreted cautiously. However, to date, CBD appears to be well tolerated. Lethargy and sedation have been the most commonly encountered adverse events, particularly in patients treated with clobazam and valproate in the background, but have been responsive to dose adjustments. Funding: No funding was received in support of this abstract.