Ohtsuka 2014

Methods	Randomised, double‐blind, placebo‐controlled, multi‐centre study in Japan. Number of control centres: not reported. Country/location: Japan. 2 treatment arms: 1 rufinamide, 1 placebo.
Participants	Participants: people aged 4‐30 years with Lennox‐Gastaut syndrome. Gender: 62% males (rufinamide group 60.7%; placebo group 63.3%). Mean age (years): 15 (rufinamide group 16.0; placebo group 13.9). Mean weight (kg): 34.7 (rufinamide group 39.0; placebo group 40.9). Ethnic groups: not reported. Median number of seizures: rufinamide group 253; placebo group 296.7. Duration of epilepsy (years): 9.9 (rufinamide group 10.5; placebo group 9.3 years). Inclusion criteria: aged 4‐30 years, weighing ≥ 15 kg with established Lennox‐Gastaut syndrome. Exclusion criteria: people with experienced tonic‐clonic status epilepticus during baseline period; if they had other clinically severe diseases or ECG/laboratory abnormalities. Diagnostic criteria: Lennox‐Gastaut syndrome diagnosed based on history of tonic or atonic (or both) seizures and atypical absence seizures and slow spike‐and‐wave complex patterns on EEG within 6 months before the baseline period. Comorbidities: none. Comedications: ≤ 3 AEDs. Total people randomised 59: rufinamide group 29; placebo group 30. 1 participant assigned to rufinamide group excluded from analysis. 5 people withdrew from study: rufinamide group 4; placebo group 1.
Interventions	Intervention: rufinamide 45 mg/kg (dose by bodyweight: 1000 mg, 1800 mg, 2400 mg or 3200 mg) per day. Control: placebo. 2‐phase study: 4‐week baseline phase and 12‐week treatment phase (2‐week titration phase followed by 10‐week maintenance phase). In addition, a 4th phase: either a follow‐up visit or entry into an open‐label extension.
Outcomes	Primary outcomes (as stated in the publication): % change in focal seizures frequency per 28 days during treatment phase relative to baseline phase. Secondary outcomes (as stated in the publication): % change in total focal seizure frequency per 28 days during the treatment phase; % responders (50%); % change in the frequency of seizures other than tonic atonic seizures for 28 days during treatment phase; adverse effects.
Notes	Stated aim of study: "This randomized trial in Japan was conducted to evaluate efficacy and tolerability (seizure control and adverse effects) and pharmacokinetics of rufinamide as an adjunctive therapy in patients with Lennox‐Gastaut syndrome." Language of publication: English. Commercial funding: yes. Publication status (peer review journal): yes. Publication status (journal supplement): no. Publication status (abstract): no. Sponsored by Eisai Pharmaceutical. No conflict of interest. Study design referred to previous trial of rufinamide for Lennox‐Gastaut syndrome (Glauser 2008). NCT01140951 and Ohtsuka 2016 (Epilepsy Research) were linked to this study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation schedule that assigned each participant to rufinamide group or placebo group in a 1:1 ratio.
Allocation concealment (selection bias)	Low risk	Participants randomised to receive rufinamide or placebo in a 1:1 ratio according to bodyweight.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participant and clinical staff blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Investigators blinded. Identical tablets and packaging.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All evaluated on ITT bias.
Selective reporting (reporting bias)	Low risk	Appeared all expected and prespecified outcomes were reported.
Other bias	High risk	Sponsored by Eisai Inc., the manufacturer of rufinamide.

AED: antiepileptic drug; CCTV: closed‐circuit television; CT: computer tomography; ECG: electrocardiograph; EEG: electroencephalogram; ITT: intention to treat; MRI: magnetic resonance imaging.