Devinsky et al.1717 Devinsky O, Cross JH, Wright S. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;377(7):699-700. https://doi.org/10.1056/NEJMc1708349 https://doi.org/10.1056/NEJMc1708349...
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RCT |
Pivotal phase 3 study; patients (n=120) diagnosed with Dravet syndrome; 2–18 years; with uncontrolled epileptic seizures, using more than one anticonvulsant drug, for more than 4 weeks. Multicenter (USA, UK, and Poland) |
Staggered dose 5.10–20 mg/kg/day divided into two times a day. Maintenance doses for 12 weeks: 20 mg/kg/day |
Placebo |
Primary: reduction in the median monthly frequency of convulsions. Secondary: change in the overall impression of caregivers and patients (S/CGIC); reduction in percentage of the number of seizures (25, 50, 75, and 100%); adverse events (number, type and severity) |
14 weeks |
Miller et al.1919 Miller I, Scheffer IE, Gunning B, Sanchez-Carpintero R, Gil-Nagel A, Perry MS, et al. Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in Dravet syndrome: a randomized clinical trial. JAMA Neurol. 2020;77(5):613-21. https://doi.org/10.1001/jamaneurol.2020.0073. Erratum in: JAMA Neurol. 2020;77(5):655. https://doi.org/10.1001/jamaneurol.2020.0749 https://doi.org/10.1001/jamaneurol.2020....
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RCT |
Pivotal phase 3 study; patients (n=199) diagnosed with Dravet Syndrome; 2–18 years; more than one anticonvulsant drug for more than 4 weeks. Multicenter (USA, Spain, Poland, the Netherlands, Australia, and Israel) |
Staggered dose 5.10–20 mg/kg/day, divided into two times a day. Maintenance doses for 12 weeks: 10 or 20 mg/kg/day |
Placebo |
Primary: reduction in the frequency of the number of convulsions. Secondary: change in the overall impression of caregivers and patients (S/CGIC); reduction in percentage of the number of seizures (25, 50, 75, and 100%); adverse events (number, type, and severity) |
14 weeks |
Devinsky et al.1818 Devinsky O, Patel AD, Thiele EA, Wong MH, Appleton R, Harden CL, et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018;90(14):e1204-e1211. https://doi.org/10.1212/WNL.0000000000005254 https://doi.org/10.1212/WNL.000000000000...
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RCT |
Patients (n=34); age between 4 and 10 years; with DS. Evaluation of pharmacokinetics and safety of cannabidiol |
Staggered dose 5.10 or 20 mg/kg/day divided into two times a day; treatment maintained for 3 weeks |
Placebo |
Dose titration and adverse events |
4 weeks |
Devinsky et al.2020 Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med. 2018;378(20):1888-97. https://doi.org/10.1056/NEJMoa1714631 https://doi.org/10.1056/NEJMoa1714631...
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RCT |
Pivotal phase 3 study; patients (n=225) with LGS; age 2–55 years; diagnosed by electroencephalographic alterations; anticonvulsants drugs for more than 4 weeks, without seizure control |
Staggered dose 5.10–20 mg/kg/day divided into two times a day. Maintenance doses for 12 weeks: 10 or 20 mg/kg/day |
Placebo |
Primary: median reduction in the number of drop seizures and total monthly seizures. Secondary: change in overall impression by caregivers and patients (S/CGIC); reduction in percentage of the number of seizures (25, 50, 75, and 100%); adverse events (number, type, and severity) |
14 weeks |
Thiele et al.2121 Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085-96. https://doi.org/10.1016/S0140-6736(18)30136-3 https://doi.org/10.1016/S0140-6736(18)30...
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RCT |
Pivotal phase 3 study; patients (n=171) with LGS; age 2–55 years; clinically diagnosed by electroencephalogram (including documented history of slow electroencephalograms [<3.0 Hz]), associated with more than one type of generalized seizure, including falls, for at least 6 previous months; on use of anticonvulsant drugs for more than 4 weeks |
Staggered dose 5.10–20 mg/kg/day divided into two times a day. Maintenance doses for 12 weeks: 20 mg/kg/day |
Placebo |
Primary: median reduction in the number of drop seizures and total monthly seizures. Secondary: change in the overall impression of caregivers ant patients (S/CGIC); reduction in percentage of the number of seizures (25, 50, 75, and 100%); adverse events (number, type and severity) |
14 weeks |
Thiele et al.2222 Thiele EA, Bebin EM, Bhathal H, Jansen FE, Kotulska K, Lawson JA, et al. Add-on cannabidiol treatment for drug-resistant seizures in tuberous sclerosis complex: a placebo-controlled randomized clinical trial. JAMA Neurol. 2021;78(3):285-92. https://doi.org/10.1001/jamaneurol.2020.4607 https://doi.org/10.1001/jamaneurol.2020....
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RCT |
Pivotal phase 3 study; patients (n=255) with diagnostic tuberous sclerosis complex; age between 1 and 65 years; using more than one anticonvulsant drug, for more than 4 weeks. (Poland, Australia, Spain, the Netherlands, UK, and USA) |
Staggered dose, with an increase of 5 mg, up to 25 or 50 mg/kg/day, divided into two doses per day. Maintenance doses for 12 weeks: 25 or 50 mg/kg/day |
Placebo |
Primary: reduction in the number of seizures. Secondary: proportion of patients with a 50% reduction in the number of seizures, change in the overall impression of patients and caregivers (S/CGIC) and adverse events |
14 weeks |