title: Normalizing effects of EVP-6124, an α-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia.
abstract: Cognitive impairment is a cause of significant disability in patients with schizophrenia. To date, no drug has been approved for this indication by the U.S. Food and Drug Administration. This article presents findings suggesting that a medication targeting the alpha-7 nicotinic acetylcholine receptor (α7 nAChR) might meet this need. This single-center, randomized, parallel-group, double-blind,placebo-controlled study examined 21 medically stable patients with schizophrenia or schizoaffective disorder treated with second generation antipsychotics. Patients were treated with a daily dose of either 0.3 mg (n=8) or 1.0 mg (n=9) of EVP-6124, an α7 nAChR partial agonist, or placebo (n=4). Treatment continued for 21 days while patients continued their usual antipsychotic medication: aripiprazole (10-30 mg/day), olanzapine (10-20 mg/day), paliperidone (3-12 mg/day), or risperidone (2-16 mg/day). Cognitive test performance, eventrelated electroencephalographic (EEG) potentials, clinical symptoms, laboratory values, and clinical side effects were measured. EVP-6124 was well tolerated and showed positive, and in some cases, dose-dependent effects on several EEG responses, especially the Mismatch Negativity and P300 potentials. Positive effects were also found in performance on cognitive tests that measured non-verbal learning, memory, and executive function. This study is an example of the type of early proof of concept trial that is done to enable drug developers to evaluate whether to continue research on an agent. Based on the promising findings in this study, larger phase II studies were initiated to further test the pro-cognitive effects of EVP-6124 in patients with chronic schizophrenia.
  
  
  BACKGROUND
  Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients with Schizophrenia, NCT01556763 http://clinicaltrials.gov/ct2/show/NCT01556763?term=NCT01556763&rank=1.
authors.affiliation: PRESKORN: University of Kansas School of Medicine-Wichita and Kansas University-Wichita Clinical Trials Unit; GAWRYL, DGETLUCK, and HILT: EnVivo Pharmaceuticals, Inc., Watertown, MA; PALFREYMAN: ChemDiv, Inc., San Diego, CA; BAUER: University of Connecticut School of Medicine, Farmington.
authors.forename: Sheldon H
authors.initials: SH
authors.lastname: Preskorn
authors.forename: Maria
authors.initials: M
authors.lastname: Gawryl
authors.forename: Nancy
authors.initials: N
authors.lastname: Dgetluck
authors.forename: Michael
authors.initials: M
authors.lastname: Palfreyman
authors.forename: Lance O
authors.initials: LO
authors.lastname: Bauer
authors.forename: Dana C
authors.initials: DC
authors.lastname: Hilt
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D003071:Cognition; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005071:Evoked Potentials / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: C573817:7-chloro-N-quinuclidin-3-yl-benzo(b)thiophene-2-carboxamide; D014150:Antipsychotic Agents; D011812:Quinuclidines; D013876:Thiophenes; D064569:alpha7 Nicotinic Acetylcholine Receptor