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Cannabidiol in patients with Lennox‐Gastaut syndrome: Interim analysis of an open‐label extension study
Author(s) -
Thiele Elizabeth,
Marsh Eric,
MazurkiewiczBeldzinska Maria,
Halford Jonathan J.,
Gunning Boudewijn,
Devinsky Orrin,
Checketts Daniel,
Roberts Claire
Publication year - 2019
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14670
Subject(s) - medicine , lennox–gastaut syndrome , concomitant , interim analysis , cannabidiol , somnolence , placebo , adverse effect , convulsion , randomized controlled trial , surgery , epilepsy , psychiatry , cannabis , alternative medicine , pathology
Summary Objective Patients with Lennox‐Gastaut syndrome ( LGS ) who completed 1 of 2 randomized, double‐blind, placebo‐controlled trials of add‐on cannabidiol ( CBD ) ( GWPCARE 3, NCT 02224560 or GWPCARE 4, NCT 02224690) were invited to enroll in an open‐label extension ( OLE ) study evaluating the long‐term safety and efficacy of CBD ( GWPCARE 5, NCT 02224573). 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 ( AE s), primarily of mild (32.5%) or moderate (43.4%) severity. The most common AE s were diarrhea (26.8%), somnolence (23.5%), and convulsion (21.3%). Thirty‐five patients (9.6%) discontinued treatment due to AE s. 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.