TY - JOUR
T1 - Time to onset of cannabidiol treatment effect and resolution of adverse events in tuberous sclerosis complex
T2 - Post hoc analysis of randomized controlled phase 3 trial GWPCARE6
AU - Wu, Joyce Y.
AU - Cock, Hannah R.
AU - Devinsky, Orrin
AU - Joshi, Charuta
AU - Miller, Ian
AU - Roberts, Colin M.
AU - Sanchez-Carpintero, Rocio
AU - Checketts, Daniel
AU - Sahebkar, Farhad
N1 - Funding Information:
The authors would like to thank the patients, their families, and the staff at sites that participated in this trial. Medical writing support for the development of this article, under the direction of the authors, was provided by Ritu Pathak, PhD, and editing support by Dena McWain, both of Ashfield MedComms, an Ashfield Health company, and funded by Greenwich Biosciences.
Funding Information:
This trial was sponsored by GW Research, Cambridge, UK.
Publisher Copyright:
© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
PY - 2022/5
Y1 - 2022/5
N2 - Objective: To estimate the timing of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]) onset, we conducted a post hoc analysis of GWPCARE6 (NCT02544763), a randomized, placebo-controlled, phase 3 trial in patients with drug-resistant epilepsy associated with tuberous sclerosis complex (TSC). Methods: Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex; 100 mg/ml oral solution) at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or placebo for 16 weeks (4-week titration, 12-week maintenance). Treatment started at 5 mg/kg/day for all groups and reached 25 mg/kg/day on Day 9 and 50 mg/kg/day on Day 29. Percentage change from baseline in TSC-associated seizure (countable focal or generalized) count was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated. Results: Of 224 patients, 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo. Median (range) age was 11.3 (1.1–56.8) years. Patients had discontinued a median (range) of 4 (0–15) antiseizure medications and were currently taking 3 (0–5). Difference in seizure reduction between CBD and placebo emerged on Day 6 (titrated dose, 15 mg/kg/day) and became nominally significant (p <.049) by Day 10. Separation between placebo and CBD in ≥50% responder rate also emerged by Day 10. Onset of AEs occurred during the first 2 weeks of the titration period in 61% of patients (CBD25, 61%; CBD50, 67%; placebo, 54%). In patients with an AE, resolution occurred within 4 weeks of onset in 42% of placebo and 27% of CBD patients and by end of trial in 78% of placebo and 51% of CBD patients. Significance: Onset of treatment effect occurred within 6–10 days. AEs lasted longer for CBD than placebo, but the most common (diarrhea, decreased appetite, and somnolence) resolved during the 16-week trial in most patients.
AB - Objective: To estimate the timing of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]) onset, we conducted a post hoc analysis of GWPCARE6 (NCT02544763), a randomized, placebo-controlled, phase 3 trial in patients with drug-resistant epilepsy associated with tuberous sclerosis complex (TSC). Methods: Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex; 100 mg/ml oral solution) at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or placebo for 16 weeks (4-week titration, 12-week maintenance). Treatment started at 5 mg/kg/day for all groups and reached 25 mg/kg/day on Day 9 and 50 mg/kg/day on Day 29. Percentage change from baseline in TSC-associated seizure (countable focal or generalized) count was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated. Results: Of 224 patients, 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo. Median (range) age was 11.3 (1.1–56.8) years. Patients had discontinued a median (range) of 4 (0–15) antiseizure medications and were currently taking 3 (0–5). Difference in seizure reduction between CBD and placebo emerged on Day 6 (titrated dose, 15 mg/kg/day) and became nominally significant (p <.049) by Day 10. Separation between placebo and CBD in ≥50% responder rate also emerged by Day 10. Onset of AEs occurred during the first 2 weeks of the titration period in 61% of patients (CBD25, 61%; CBD50, 67%; placebo, 54%). In patients with an AE, resolution occurred within 4 weeks of onset in 42% of placebo and 27% of CBD patients and by end of trial in 78% of placebo and 51% of CBD patients. Significance: Onset of treatment effect occurred within 6–10 days. AEs lasted longer for CBD than placebo, but the most common (diarrhea, decreased appetite, and somnolence) resolved during the 16-week trial in most patients.
KW - antiseizure medication
KW - cannabidiol
KW - epilepsy
KW - focal seizures
KW - medication-resistant seizures
KW - tuberous sclerosis complex
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U2 - 10.1111/epi.17199
DO - 10.1111/epi.17199
M3 - Article
C2 - 35175622
AN - SCOPUS:85125587696
SN - 0013-9580
VL - 63
SP - 1189
EP - 1199
JO - Epilepsia
JF - Epilepsia
IS - 5
ER -