Time to onset of cannabidiol treatment effect and resolution of adverse events in tuberous sclerosis complex: Post hoc analysis of randomized controlled phase 3 trial GWPCARE6.
Epilepsia
; 63(5): 1189-1199, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35175622
ABSTRACT
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esclerose Tuberosa
/
Canabidiol
Tipo de estudo:
Clinical_trials
/
Etiology_studies
Limite:
Adolescent
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Adult
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Child
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Humans
/
Middle aged
Idioma:
En
Revista:
Epilepsia
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos