Glauser 2008.

Study characteristics
Methods	Randomised, double‐blind, placebo‐controlled, parallel‐group, multi‐centre study Number of control centres: 36 Country/Location: Belgium, Brazil, Germany, Hungary, Italy, Norway, Poland, Spain, and USA 2 treatment arms: 1 rufinamide, 1 placebo
Participants	Participants: aged 4 to 30 years with Lennox‐Gastaut syndrome Gender: 62.3% males (rufinamide group 62.2%; placebo group 62.5%) Median age (years): 12.0 (rufinamide group 13.0; placebo group 10.5%) Median weight (kg): 34.7 (rufinamide group 35.9; placebo group 33.5) Ethnic groups: white 83.3%, black 7.2%, other 9.5% Median number of seizures: rufinamide group 290; placebo group 205 Duration of epilepsy (years): 7.7 (rufinamide group 7.9; placebo group 7.5) Inclusion criteria: aged 4 to 30 years with established Lennox‐Gastaut syndrome; minimum of 90 seizures in month before the 28‐day baseline period; EEG within 6 months of study entry demonstrating a pattern of slow spike‐and‐wave complexes (< 2.5 Hz); weight ≥ 18 kg; fixed‐dose regimen of 1 to 3 concomitant AEDs during the baseline period; CT scan or MRI study confirming absence of a progressive lesion Exclusion criteria: ≥ 3 AEDs; pregnant or not using adequate contraception; correctable aetiology of seizures (active infection, neoplasm, metabolic disturbance); history of generalised tonic‐clonic status epilepticus within 30 days before baseline; history of any clinically significant non‐neurological medical condition Diagnostic criteria: Lennox‐Gastaut syndrome was diagnosed based on a 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 baseline period Comorbidities: none Comedications: ≤ 2 AEDs Total people randomised: 139 (1 patient was excluded from analysis): rufinamide group 74; placebo group 64. 15 people withdrew from the study: rufinamide group 10; placebo group 5
Interventions	Intervention: rufinamide 45 mg/kg (dose by body weight: 1000 mg, 1800 mg, 2400 mg, and 3200 mg) per day Control: placebo 2‐phase study: 28‐day pre‐randomisation baseline phase and 84‐day treatment phase (14‐day titration phase followed by 70‐day maintenance phase)
Outcomes	Primary outcomes (as stated in the publication) Median % reduction in total seizure frequency per 28 days during treatment phase relative to baseline Median percentage reduction in tonic‐atonic seizure frequency per 28 days during treatment phase relative to baseline Seizure severity rating from global evaluation of the participant's condition Secondary outcomes (as stated in the publication) % responders (50%) Adverse effects
Notes	Stated aim of study: "this randomized trial was conducted to evaluate efficacy and tolerability (seizure control and adverse effects) of rufinamide 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 Pharmaceuticals and conducted by Novartis Pharmaceuticals No conflict of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants randomised in blocks of 4 to receive either rufinamide or matching placebo
Allocation concealment (selection bias)	Low risk	Sequential numbers assigned at each site during the first visit
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Identical tablets and packaging
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Details of outcome assessment blinding not provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition rates reported. ITT efficacy analysis employed
Selective reporting (reporting bias)	Low risk	Protocol unavailable but appeared all expected and pre‐specified outcomes were reported
Other bias	High risk	Sponsored by Eisai Inc., the manufacturer of rufinamide