Ohtsuka 2014.

Study characteristics
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 to 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 to 30 years, weighing ≥ 15 kg with established Lennox‐Gastaut syndrome Exclusion criteria: people with experienced tonic‐clonic status epilepticus during baseline period; those with 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 body weight: 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 fourth phase: either a follow‐up visit or entry into an open‐label extension
Outcomes	Primary outcomes (as stated in the publication) % change in focal seizure 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)
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 body weight
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants 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 pre‐specified outcomes were reported
Other bias	High risk	Sponsored by Eisai Inc., the manufacturer of rufinamide

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