Long-term Safety and Efficacy of Add-on Cannabidiol (CBD) for Treatment of Seizures Associated with Tuberous Sclerosis Complex (TSC) in an Open-Label Extension (OLE) Trial (GWPCARE6)
Abstract number :
124
Submission category :
7. Antiepileptic Drugs / 7B. Clinical Trials
Year :
2020
Submission ID :
2422472
Source :
www.aesnet.org
Presentation date :
12/5/2020 9:07:12 AM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Elizabeth A. Thiele, Massachusetts General Hospital; E. Martina Bebin - University of Alabama at Birmingham School of Medicine; Francis Filloux, MD - University of Utah School of Medicine; Patrick Kwan - Monash University and The Royal Melbourne Hospital,
Rationale:
Add-on CBD reduced TSC-associated seizures with an acceptable safety profile in a randomized, placebo-controlled phase 3 trial (GWPCARE6; NCT02544763). To evaluate long-term safety and efficacy of CBD, patients were enrolled in an OLE. In this 2nd interim analysis, we report safety for the full follow-up and efficacy through 72 wks of treatment in the OLE.
Method:
Patients who completed the randomized controlled trial (RCT) could enroll to receive plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution). Initially, dose was titrated up to 25 mg/kg/d, which could be decreased or increased up to 50 mg/kg/d based on response and tolerability. The primary endpoint was safety. Secondary endpoints included percentage change from RCT baseline in TSC-associated (countable focal and generalized) seizure frequency per 28 days and responder rates (≥50%, ≥75%, and 100% reduction) evaluated at 12-wk windows throughout treatment. Changes in patients’ overall condition on Subject/Caregiver Global Impression of Change (S/CGIC) scale from baseline to 26 and 52 wks were assessed.
Results:
Of 201 patients who completed the RCT, 199 (99%) entered the OLE. Median (range) age at RCT baseline: 10.7 yrs (1.1–56.8). Median (range) number of AEDs at baseline: 3 (0–5). Most common concomitant AEDs during OLE: valproate (42%), vigabatrin (37%), and clobazam (34%). Median (Q1, Q3) monthly TSC-associated seizure frequency at baseline: 57 (28, 109). At the time of this analysis, 12% of patients had completed treatment, 31% had withdrawn, and 57% were ongoing. Median treatment time (range) during OLE: 372 d (18–1127). The mean (SD) of patients’ modal CBD dose was 28 mg/kg/d (9); 145 (73%) were treated with modal dose ≤25 mg/kg/d and 54 (27%) with >25 mg/kg/d. AEs were reported by 94% of patients, serious AEs by 26%, and 8% discontinued treatment due to an AE. Most frequently reported AEs: diarrhea and seizures (Table 1). Seventeen (9%) patients had elevated ALT/AST >3×ULN; 12 of these (71%) were on concomitant valproate. No patient met Hy’s law criteria for severe liver injury. There was 1 death due to cardiopulmonary failure, deemed not treatment related by the investigator. Median percentage reduction from baseline in TSC-associated seizures ranged from 53%–75% across 12-wk windows through 72 wks. Last observation carried forward analysis showed similar results and ranged from 52%–63%. Seizure reductions ranged from 54%–80% for patients (n=145) with a modal dose ≤25 mg/kg/d. ≥50%, ≥75%, and 100% reductions in TSC-associated seizures were maintained up to 72 wks, ranging from 52%–63%, 29%–51%, and 6%–19%, respectively across 12-wk windows. Improvement on S/CGIC was reported by 141/165 patients/caregivers (85%) at 26 wks and 83/93 (89%) at 52 wks.
Conclusion:
Add-on CBD treatment was well tolerated and produced sustained reductions in TSC-associated seizures for up to 72 wks, supporting long-term use of CBD for treatment of seizures associated with TSC.
Funding:
:GW Research Ltd
Antiepileptic Drugs