title: A randomized exploratory trial of an α-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia.
abstract: This exploratory trial was conducted to test the effects of an alpha7 nicotinic receptor partial agonist, TC-5619, on cognitive dysfunction and negative symptoms in subjects with schizophrenia. In the United States and India, 185 outpatients (18-60 years; male 69%; 46% tobacco users) with schizophrenia treated with quetiapine or risperidone monotherapy were randomized to 12 weeks of placebo (n=91) or TC-5619 (n=94; orally once daily 1 mg day 1 to week 4, 5 mg week 4 to 8, and 25 mg week 8 to 12). The primary efficacy outcome measure was the Groton Maze Learning Task (GMLT; executive function) of the CogState Schizophrenia Battery (CSB). Secondary outcome measures included: CSB composite score; Scale for Assessment of Negative Symptoms (SANS); Clinical Global Impression-Global Improvement (CGI-I); CGI-severity (CGI-S); and Subject Global Impression-Cognition. GMLT statistically favored TC-5619 (P=0.036) in this exploratory trial. SANS also statistically favored TC-5619 (P=0.030). No other secondary outcome measure demonstrated a drug effect in the total population; there was a statistically significant drug effect on working memory in tobacco users. The results were typically stronger in favor of TC-5619 in tobacco users and occasionally better in the United States than in India. TC-5619 was generally well tolerated with no clinically noteworthy safety findings. These results support the potential benefits of TC-5619 and alpha7 nicotinic receptor partial agonists for cognitive dysfunction and negative symptoms in schizophrenia.
authors.affiliation: Department of Psychiatry, Columbia College of Physicians and Surgeons, New York, NY 10032, USA. jlieberman@columbia.edu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Dunbar
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Segreti
authors.forename: Ragy R
authors.initials: RR
authors.lastname: Girgis
authors.forename: Frances
authors.initials: F
authors.lastname: Seoane
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Beaver
authors.forename: Naihua
authors.initials: N
authors.lastname: Duan
authors.forename: David A
authors.initials: DA
authors.lastname: Hosford
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001572:Benzofurans / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000627:therapeutic use*; D011812:Quinuclidines / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology; D012565:Schizophrenic Psychology; D014481:United States / Q000453:epidemiology; D055815:Young Adult; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000502:physiology*
chemical_list: D014150:Antipsychotic Agents; D001572:Benzofurans; C543641:N-(2-(pyridin-3-ylmethyl)-1-azabicyclo(2.2.2)oct-3-yl)-1-benzofuran-2-carboxamide; D018722:Nicotinic Agonists; D018697:Nootropic Agents; D011812:Quinuclidines; D064569:alpha7 Nicotinic Acetylcholine Receptor