Abstract | OBJECTIVE: Patients with Lennox-Gastaut syndrome (LGS) who completed 1 of 2 randomized, double-blind, placebo-controlled trials of add-on cannabidiol (CBD) (GWPCARE3, NCT02224560 or GWPCARE4, NCT02224690) were invited to enroll in an open-label extension (OLE) study evaluating the long-term safety and efficacy of CBD (GWPCARE5, NCT02224573). Herein we present an interim analysis of the safety, efficacy, and patient-reported outcomes from this trial. METHODS: Patients received a pharmaceutical formulation of highly purified CBD oral solution ( Epidiolex; 100 mg/mL), titrated from 2.5 to 20 mg/kg/d over a 2-week titration period, in addition to their existing medications. Doses could be reduced if not tolerated or increased up to 30 mg/kg/d if thought to be of benefit. RESULTS: This interim analysis was based on a November 2016 data cut. Of 368 patients who completed treatment in GWPCARE3 and GWPCARE4, 366 (99.5%) enrolled in the OLE study (GWPCARE5). Median treatment duration was 38 weeks at a mean modal dose of 23 mg/kg/d. Most patients (92.1%) experienced adverse events (AEs), primarily of mild (32.5%) or moderate (43.4%) severity. The most common AEs were diarrhea (26.8%), somnolence (23.5%), and convulsion (21.3%). Thirty-five patients (9.6%) discontinued treatment due to AEs. Liver transaminase elevations were reported in 37 patients (10.1%), of whom 29 were receiving concomitant valproic acid; 34 cases resolved spontaneously or with dose modification of CBD or concomitant medication. Median reduction from baseline in drop seizure frequency (quantified monthly over 12-week periods) ranged from 48% to 60% through week 48. Median reduction in monthly total seizure frequency ranged from 48% to 57% across all 12-week periods through week 48. Eighty-eight percent of patients/caregivers reported an improvement in the patient's overall condition per the Subject/Caregiver Global Impression of Change scale. SIGNIFICANCE: In this study, long-term add-on CBD treatment had an acceptable safety profile in patients with LGS and led to sustained reductions in seizures.
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Authors | Elizabeth Thiele, Eric Marsh, Maria Mazurkiewicz-Beldzinska, Jonathan J Halford, Boudewijn Gunning, Orrin Devinsky, Daniel Checketts, Claire Roberts |
Journal | Epilepsia
(Epilepsia)
Vol. 60
Issue 3
Pg. 419-428
(03 2019)
ISSN: 1528-1167 [Electronic] United States |
PMID | 30740695
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © 2019 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy. |
Chemical References |
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Topics |
- Adolescent
- Adult
- Cannabidiol
(administration & dosage, adverse effects, therapeutic use)
- Child
- Child, Preschool
- Double-Blind Method
- Female
- Humans
- Lennox Gastaut Syndrome
(drug therapy)
- Male
- Middle Aged
- Seizures
(prevention & control)
- Treatment Outcome
- Young Adult
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