6 research outputs found
Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome A Randomized Clinical Trial
Question Is adjunctive cannabidiol at doses of 10 and 20 mg/kg/d
superior to placebo in reducing convulsive seizure frequency in
patients with Dravet syndrome?
Findings This double-blind clinical trial randomized 199 children
with Dravet syndrome to cannabidiol (10 or 20 mg/kg/d) or
matched placebo for 14 weeks. Convulsive seizure frequency
compared with baseline was reduced by 48.7% in the 10-mg/kg/d
cannabidiol group and 45.7% in the 20-mg/kg/d cannabidiol
group vs 26.9% in the placebo group.
Meaning Both doses of adjunctive cannabidiol were similarly
efficacious in reducing convulsive seizures associated with Dravet
syndrome
Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome
Background:
Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the LennoxâGastaut syndrome, a severe developmental epileptic encephalopathy.
Methods:
In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the LennoxâGastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period.
Results:
A total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percent reduction from baseline in drop-seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P=0.005 for the 20-mg cannabidiol group vs. placebo group, and P=0.002 for the 10-mg cannabidiol group vs. placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher-dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations.
Conclusions:
Among children and adults with the LennoxâGastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations. (Funded by GW Pharmaceuticals; GWPCARE3 ClinicalTrials.gov number, NCT02224560.
Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome A Randomized Clinical Trial
Question Is adjunctive cannabidiol at doses of 10 and 20 mg/kg/d
superior to placebo in reducing convulsive seizure frequency in
patients with Dravet syndrome?
Findings This double-blind clinical trial randomized 199 children
with Dravet syndrome to cannabidiol (10 or 20 mg/kg/d) or
matched placebo for 14 weeks. Convulsive seizure frequency
compared with baseline was reduced by 48.7% in the 10-mg/kg/d
cannabidiol group and 45.7% in the 20-mg/kg/d cannabidiol
group vs 26.9% in the placebo group.
Meaning Both doses of adjunctive cannabidiol were similarly
efficacious in reducing convulsive seizures associated with Dravet
syndrome
Add-Âon cannabidiol in patients with Dravet syndrome: Results of a long-Âterm open-Âlabel extension trial
Objective: Add-on cannabidiol (CBD) reduced seizures associated with Dravet
syndrome (DS) in two randomized, double-blind, placebo-controlled trials:
GWPCARE1 Part B (NCT02091375) and GWPCARE2 (NCT02224703). Patients
whocompletedGWPCARE1 PartA(NCT02091206)orPartB,orGWPCARE2,were
enrolled in a long-term open-label extension trial, GWPCARE5 (NCT02224573).
We present an interim analysis of the safety, efficacy, and patient-reported outcomes from GWPCARE5.
Methods: Patientsreceived a pharmaceutical formulation of highly purified CBD
in oral solution (100 mg/ml), titrated from 2.5 to 20 mg/kg/day over a 2-week period, added to their existing medications. Based on response and tolerance, CBD
could be reduced or increased to 30 mg/kg/day.
Results: Of the 330 patients who completed the original randomized trials, 315
(95%) enrolled in this open-label extension. Median treatment duration was
444 days (range = 18â1535), with a mean modal dose of 22 mg/kg/day; patients
received a median of three concomitant antiseizure medications. Adverse events
(AEs)occurredin97%patients(mild,23%;moderate,50%;severe,25%).Commonly
reported AEs were diarrhea (43%), pyrexia (39%), decreased appetite (31%), and
somnolence (28%). Twenty-eight (9%) patients discontinued due to AEs. Sixtynine (22%) patients had liver transaminase elevations >3 Ă upper limit of normal;
84% were on concomitant valproic acid. In patients from GWPCARE1 Part B and
GWPCARE2, the median reduction from baseline in monthly seizure frequency
assessed in 12-week periods up to Week 156 was 45%â74% for convulsive seizures
and 49%â84% for total seizures. Across all visit windows, â„83% patients/caregivers completing a Subject/Caregiver Global Impression of Change scale reported
improvement in overall condition.
Significance: We show that long-term CBD treatment had an acceptable safety
profile and led to sustained, clinically meaningful reductionsin seizure frequency
in patients with treatment-resistant DS