title: Phase 2 Trial of an Alpha-7 Nicotinic Receptor Agonist (TC-5619) in Negative and Cognitive Symptoms of Schizophrenia.
abstract: OBJECTIVE
  This trial was conducted to test the effects of an alpha7 nicotinic receptor full agonist, TC-5619, on negative and cognitive symptoms in subjects with schizophrenia.
  
  
  METHODS
  In 64 sites in the United States, Russia, Ukraine, Hungary, Romania, and Serbia, 477 outpatients (18-65 years; male 62%; 55% tobacco users) with schizophrenia, treated with a new-generation antipsychotic, were randomized to 24 weeks of placebo (n = 235), TC-5619, 5mg (n = 121), or TC-5619, 50 mg (n = 121), administered orally once daily. The primary efficacy measure was the Scale for the Assessment of Negative Symptoms (SANS) composite score. Key secondary measures were the Cogstate Schizophrenia Battery (CSB) composite score and the University of California San Diego Performance-Based Skills Assessment-Brief Version (UPSA-B) total score. Secondary measures included: Positive and Negative Syndrome Scale in Schizophrenia (PANSS) total and subscale scores, SANS domain scores, CSB item scores, Clinical Global Impression-Global Improvement (CGI-I) score, CGI-Severity (CGI-S) score, and Subject Global Impression-Cognition (SGI-Cog) total score.
  
  
  RESULTS
  SANS score showed no statistical benefit for TC-5619 vs placebo at week 24 (5 mg, 2-tailed P = .159; 50 mg, P = .689). Likewise, no scores of CSB, UPSA-B, PANSS, CGI-I, CGI-S, or SGI-Cog favored TC-5619 (P > .05). Sporadic statistical benefit favoring TC-5619 in some of these outcome measures were observed in tobacco users, but these benefits did not show concordance by dose, country, gender, or other relevant measures. TC-5619 was generally well tolerated.
  
  
  CONCLUSIONS
  These results do not support a benefit of TC-5619 for negative or cognitive symptoms in schizophrenia.
authors.affiliation: CNS Network, Inc., Garden Grove, CA; davidwalling@cnstrial.com.
authors.forename: David
authors.initials: D
authors.lastname: Walling
authors.affiliation: Desert Pacific Mental Illness Research, Education, and Clinical Center UCLA Semel Institute for Neuroscience, Los Angeles, CA;
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Marder
authors.affiliation: Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY;
authors.forename: John
authors.initials: J
authors.lastname: Kane
authors.affiliation: Department for Psychiatry and Psychotherapy, Division of Biological Psychiatry, Medical University Innsbruck, Innsbruck, Austria;
authors.forename: W Wolfgang
authors.initials: WW
authors.lastname: Fleischhacker
authors.affiliation: Schizophrenia Research Group, Psychiatry & Behavioral Sciences, Division of Medical Psychology, School of Medicine, Duke University, Durham, NC;
authors.forename: Richard S E
authors.initials: RS
authors.lastname: Keefe
authors.affiliation: Department of Clinical Development and Regulatory Affairs, Targacept Inc., Winston-Salem, NC.
authors.forename: David A
authors.initials: DA
authors.lastname: Hosford
authors.affiliation: Department of Clinical Development and Regulatory Affairs, Targacept Inc., Winston-Salem, NC.
authors.forename: Chris
authors.initials: C
authors.lastname: Dvergsten
authors.affiliation: Department of Clinical Development and Regulatory Affairs, Targacept Inc., Winston-Salem, NC.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Segreti
authors.affiliation: Department of Clinical Development and Regulatory Affairs, Targacept Inc., Winston-Salem, NC.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Beaver
authors.affiliation: Department of Clinical Development and Regulatory Affairs, Targacept Inc., Winston-Salem, NC.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Toler
authors.affiliation: Department of Clinical Development and Regulatory Affairs, Targacept Inc., Winston-Salem, NC.
authors.forename: John E
authors.initials: JE
authors.lastname: Jett
authors.affiliation: Department of Clinical Development and Regulatory Affairs, Targacept Inc., Winston-Salem, NC.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Dunbar
mesh_terms: D000328:Adult; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D011812:Quinuclidines / Q000008:administration & dosage / Q000494:pharmacology*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology*; D012720:Severity of Illness Index; D055815:Young Adult; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: D001572:Benzofurans; C543641:N-(2-(pyridin-3-ylmethyl)-1-azabicyclo(2.2.2)oct-3-yl)-1-benzofuran-2-carboxamide; D018722:Nicotinic Agonists; D011812:Quinuclidines; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: cognition; negative symptoms; schizophrenia