title: Randomized, Double-Blind, Placebo-Controlled Study of Encenicline, an α7 Nicotinic Acetylcholine Receptor Agonist, as a Treatment for Cognitive Impairment in Schizophrenia.
abstract: Encenicline is a novel, selective α7 nicotinic acetylcholine receptor agonist in development for treating cognitive impairment in schizophrenia and Alzheimer's disease. A phase 2, double-blind, randomized, placebo-controlled, parallel-design, multinational study was conducted. Patients with schizophrenia on chronic stable atypical antipsychotics were randomized to encenicline 0.27 or 0.9 mg once daily or placebo for 12 weeks. The primary efficacy end point was the Overall Cognition Index (OCI) score from the CogState computerized battery. Secondary end points include MATRICS Consensus Cognitive Battery (MCCB) (in US patients), the Schizophrenia Cognition Rating Scale (SCoRS) total score, SCoRS global rating, and Positive and Negative Syndrome Scale (PANSS) total and subscale and cognition factor scores. Of 319 randomized patients, 317 were included in the safety population, and 307 were included in the intent-to-treat population. Notable trends in improvement were demonstrated across all cognition scales. For the OCI score, the LS mean difference for encenicline 0.27 mg vs placebo was significant (Cohen's d=0.257; P=0.034). Mean SCoRS total scores decreased showing improvement in function over time, and the difference was significant for encenicline 0.9 mg vs placebo (P=0.011). Furthermore, the difference between encenicline 0.9 mg and placebo was significant for the PANSS Cognition Impairment Domain (P=0.0098, Cohen's d=0.40) and for the PANSS Negative scale (P=0.028, Cohen's d=0.33). Treatment-emergent adverse events were reported at similar frequencies across all treatment groups (39.0% with placebo, 23.4% with encenicline 0.27 mg, and 33.3% with encenicline 0.9 mg). Overall, encenicline was generally well tolerated and demonstrated clinically meaningful improvements in cognition and function in patients with schizophrenia.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: Richard S E
authors.initials: RS
authors.lastname: Keefe
authors.affiliation: Department of Psychiatry and Behavioral Sciences Psychiatry, Northwestern University, Feinberg School of Medicine, USA.
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Meltzer
authors.affiliation: FORUM Pharmaceuticals Inc., Waltham, MA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Dgetluck
authors.affiliation: FORUM Pharmaceuticals Inc., Waltham, MA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Gawryl
authors.affiliation: FORUM Pharmaceuticals Inc., Waltham, MA, USA.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Koenig
authors.affiliation: FORUM Pharmaceuticals Inc., Waltham, MA, USA.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Moebius
authors.affiliation: FORUM Pharmaceuticals Inc., Waltham, MA, USA.
authors.forename: Ilise
authors.initials: I
authors.lastname: Lombardo
authors.affiliation: FORUM Pharmaceuticals Inc., Waltham, MA, USA.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Hilt
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000627:therapeutic use*; D011812:Quinuclidines / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; C000605814:N-(7-chloro-N-quinuclidin-3-yl)benzo(b)thiophene-2-carboxamide; D018722:Nicotinic Agonists; D011619:Psychotropic Drugs; D011812:Quinuclidines; D013876:Thiophenes; D064569:alpha7 Nicotinic Acetylcholine Receptor