Annual Meeting Abstracts: View

  • (Abst. 1.289), 2017
  • Maintenance of Long-Term Safety and Efficacy of Cannabidiol (CBD) Treatment in Dravet Syndrome (DS): Results of the Open-Label Extension (OLE) Trial (GWPCARE 5)
  • Authors: Orrin Devinsky, NYU Langone Medical Center, New York, NY, USA; Rima Nabbout, Necker-Enfants Malades Hospital; Ian Miller, Miami Children's Hospital; Linda Laux, Ann and Robert H. Lurie Children’s Hospital of Chicago; Martha Zolnowska, Centrum Medyczne Pleajady; Stephen Wright, GW Research Ltd; and Claire Roberts, GW Research Ltd
  • Content:

    Rationale: The efficacy and safety of CBD in the treatment of seizures associated with DS has been demonstrated in the controlled trial GWPCARE 1. Here we present a pre-specified interim analysis of an OLE study (GWPCARE 5; NCT02224573) designed to assess the long-term safety and efficacy of CBD as add-on to existing antiepileptic drug (AED) treatment in patients (pts) with treatment-resistant DS. Methods: Children and adults who had previously participated in a 14-week (wk), double-blind, randomized, controlled DS trial (GWPCARE 1 [NCT02091375] or GWPCARE 2 [NCT02224703]) could enroll into the OLE and be treated for up to 2 years (y) with a plant-derived pharmaceutical formulation of CBD (100 mg/mL) in oral solution. Initially, pts were titrated to 20 mg/kg/day (d), which could then be either decreased or increased up to 30 mg/kg/d at the investigator’s discretion. The primary endpoint was safety, with key secondary endpoints of convulsive and total seizure frequency and the Subject/Caregiver Global Impression of Change (S/CGIC). This is the first of two planned interim analyses to support regulatory submissions, with a cut-off date 03Nov2016. As GWPCARE 2 is ongoing and still blinded, original baseline data, or data expressed as a percent of original baseline, include pts from GWPCARE 1 only. Results: A total of 264 pts with DS enrolled from GWPCARE 1 and GWPCARE 2; at time of analysis 75 had withdrawn, including 17 for adverse events (AEs). Pts were age 3-19 y; mean age 10 y and 50% male. Pts were taking a median of 3 concomitant AEDs (clobazam 68%; valproic acid 64%). Mean modal dose for the treatment phase was 21 mg/kg/d (min 2.5, max 30; n=257). Pts were exposed for a mean of 36 weeks (range 1 d to 73 wks). AEs occurred in 93% of pts and were considered treatment-related in 64%. Of pts reporting an AE, 76% had AEs that were mild or moderate. AEs occurring in ≥10% of patients were diarrhea, pyrexia, decreased appetite, somnolence, nasopharyngitis, convulsion, vomiting, upper respiratory tract infection, status epilepticus, and fatigue. Some elevations in transaminases were reported. Serious AEs were reported in 29% of pts and were considered treatment-related in 8%. There were 2 deaths; neither was deemed treatment-related. In pts with baseline data available, median monthly convulsive seizures decreased by 38%–57% from 12.4 at baseline, and median monthly total seizures decreased by 40%–60% from 32.4 at baseline, when analyzed over five 12-wk periods (Table 1). An improvement in overall condition on the S/CGIC was reported by 81% and 84% of pts/caregivers at wks 24 and 48, respectively (Table 2). Conclusions: Long-term add-on CBD treatment continued to be generally well tolerated, with a similar AE profile to that observed in previous controlled trial of CBD in DS. Results showed a reduction in both convulsive and total seizure frequency through 60 wks of exposure with a high proportion of pts/caregivers reporting an improvement in overall condition. Funding: GW Research Ltd
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