title: Randomized, multicenter trial to assess the efficacy, safety and tolerability of a single dose of a novel AMPA receptor antagonist BGG492 for the treatment of acute migraine attacks.
abstract: BACKGROUND
  Glutamate is implicated in migraine pathophysiology; amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists represent a potential therapeutic approach because of their anti-excitatory actions.
  
  
  METHODS
  This randomized, double-blind, proof-of-concept study assessed the efficacy of the AMPA receptor antagonist, BGG492 (250 mg), vs placebo and sumatriptan (100 mg), in 75 subjects with acute migraine attacks. Efficacy was measured using the Patient Migraine Diary. Pharmacokinetic and safety data were collected.
  
  
  RESULTS
  Improvement from severe/moderate to mild/no headache pain (primary response) was reported in 58%, 58%, and 54% of BGG492-treated subjects at 2, 3, and 4 hours post-dose ( P = 0.2, 0.5, and 0.5 vs placebo), respectively, compared with 68%, 84%, and 92% sumatriptan-treated subjects, and 40%, 48%, and 44% in the placebo group. Percentages of subjects with ≥ 2-point improvement in pain score from baseline at 2 hours were 29%, 40%, and 16% for BGG492, sumatriptan, and placebo, respectively. Pain-free response at 2 hours was reported for 25%, 24%, and 16% of BGG492, sumatriptan, and placebo subjects, respectively. Adverse events were reported by 80%, 56%, and 60% of BGG492, sumatriptan, and placebo subjects, respectively.
  
  
  CONCLUSIONS
  Proof-of-concept criterion was not met (≥ 25% BGG492 subjects with a primary response vs placebo at two timepoints). BGG492 was comparable to sumatriptan in terms of pain-free response.
authors: Neuroscience Translational Medicine, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Switzerland.
authors: Baltazar
authors: B
authors: Gomez-Mancilla
authors: Ronald
authors: R
authors: Brand
authors: Tim P
authors: TP
authors: Jürgens
authors: Harmut
authors: H
authors: Göbel
authors: Claudia
authors: C
authors: Sommer
authors: Andreas
authors: A
authors: Straube
authors: Stefan
authors: S
authors: Evers
authors: Martin
authors: M
authors: Sommer
authors: Victor
authors: V
authors: Campos
authors: Hans O
authors: HO
authors: Kalkman
authors: Sam
authors: S
authors: Hariry
authors: Nicole
authors: N
authors: Pezous
authors: Donald
authors: D
authors: Johns
authors: Hans-Christoph
authors: HC
authors: Diener
mesh_terms: D000208:Acute Disease; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D010919:Placebos; D052999:Quinazolinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018170:Sumatriptan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D010919:Placebos; D052999:Quinazolinones; D018091:Receptors, AMPA; D058825:Serotonin 5-HT1 Receptor Agonists; C000591013:selurampanel; D018170:Sumatriptan
keywords: AMPA receptor antagonist; Migraine attack; sumatriptan