title: Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies.
abstract: OBJECTIVE
  To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults.
  
  
  METHODS
  Data were pooled from patients (aged 16-80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool.
  
  
  RESULTS
  In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%-29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%-31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%-31.8%) for 200 mg/d (p < 0.00001). The ≥50% responder rate was 34.2% (50 mg/d, p = 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment-emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n = 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in ≥5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%).
  
  
  CONCLUSIONS
  Adjunctive BRV was effective and generally well tolerated in adults with POS.
  
  
  METHODS
  This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures.
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK. Elinor.Ben-Menachem@neuro.gu.se.
authors.forename: Elinor
authors.initials: E
authors.lastname: Ben-Menachem
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK.
authors.forename: Rūta
authors.initials: R
authors.lastname: Mameniškienė
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Quarato
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK.
authors.forename: Pavel
authors.initials: P
authors.lastname: Klein
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Gamage
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Schiemann
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Johnson
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK.
authors.forename: John
authors.initials: J
authors.lastname: Whitesides
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK.
authors.forename: Belinda
authors.initials: B
authors.lastname: McDonough
authors.affiliation: From the Institute for Clinical Neuroscience and Physiology (E.B.-M.), Sahlgrenska Academy, University of Gothenburg, Sweden; Clinic of Neurology and Neurosurgery (R.M.), Medical Faculty, Vilnius University; Neurology Centre (R.M.), Vilnius University Hospital Santariškių Klinikos, Vilnius, Lithuania; IRCCS Instituto Neurologico (P.P.Q.), Centro per la Chirurgia dell'Epilessia, Pozzilli, Italy; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; QXV Communications (J.G.), Macclesfield, UK; UCB Pharma (J.S., M.E.J., J.W., K.E.), Raleigh, NC; and UCB Pharma (B.M.), Slough, UK.
authors.forename: Klaus
authors.initials: K
authors.lastname: Eckhardt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D011760:Pyrrolidinones; D000077287:Levetiracetam; C482793:brivaracetam; D010889:Piracetam