Biton 2011

Methods	Randomised, double‐blind, placebo‐controlled, parallel‐group multi‐centre study. Number of control centres: 65. Country/location: US and Canada. 2 treatment arms: 1 rufinamide, 1 placebo.
Participants	Participants: adolescents and adults (aged 12‐80 years) with inadequately controlled focal‐onset seizures. Gender: 46.9% male (rufinamide group 47.7%; placebo group 46.1%). Mean age (years): 37.3 (rufinamide group 36.4; placebo group 38.1). Mean weight (kg): 78.2 (rufinamide group 77.4; placebo group 79.0). Ethnic groups: black 9.3%; white 80.1%, Hispanic 7.6%; other 3.0%. Median number of seizures: 13.3 (rufinamide group 13; placebo group 13.8). Duration of epilepsy: not reported. Inclusion criteria: males or females, aged 12‐80 years, with focal‐onset seizures with or without secondarily generalised seizures; person's seizures inadequately controlled on stable doses of up to 3 concomitantly administered AEDs, with no evidence of AED treatment non‐compliance. Exclusion criteria: known generalised epilepsies or history of status epilepticus or seizure clusters in the past year, or if they required felbamate, vigabatrin or rescue benzodiazepines; moreover, if they had clinically significant medical or psychiatric disease, clinically significant ECG abnormality, or a diagnosis of congenital short QT syndrome, psychogenic seizures in the previous year, history of drug abuse and/or positive finding on urinary drug screening, or a history of alcohol abuse in the past 2 years. Diagnostic criteria: established by clinical history, electroencephalography, and CT/MRI of the brain performed within the last 10 years. Comorbidities: none. Comedications: ≤ 3 AEDs. Total people randomised 357: rufinamide group 176; placebo group 181. One participant was excluded from the analysis because required laboratory assessments were not obtained. 61 people withdrew from study: rufinamide group 37; placebo group 24.
Interventions	Intervention: rufinamide 3200 mg/day Control: placebo. 2‐phase study: 56‐day baseline/screening phase; and 96‐day treatment phase (12‐day titration period followed by 84‐day maintenance phase).
Outcomes	Primary outcomes (as stated in publication): % change in total focal seizures frequency per 28 days during maintenance phase relative to baseline. Secondary outcomes (as stated in publication): % responders (50% and 75%); adverse effects.
Notes	Stated aim of study: "This randomized study was conducted to evaluate and confirm the efficacy and safety (seizure control and adverse effects) of rufinamide as adjunctive treatment for refractory focal‐onset seizures." Language of publication: English. Commercial funding: yes. Publication status (peer review journal): yes. Publication status (journal supplement): no. Publication status (abstract): no. Funded by Eisai Medical Research. No conflict of interest. NCT00334958 is linked to this study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated schedule using blocks of 4.
Allocation concealment (selection bias)	Low risk	Allocated participants to each of the 2 treatment groups in a 1:1 ratio.
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.
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 prespecified outcomes were reported.
Other bias	High risk	Sponsored by Eisai Inc., the manufacturer of rufinamide.