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Psych Congress  

Encenicline, a Potentiator of α7 Receptor Signaling: Effects on Cognition and Clinical Function in Patients with Chronic Schizophrenia on Stable Antipsychotic Therapy

Ilise Lombardo, MD
Nancy Dgetluck, PhD
Gerhard Koenig, PhD
Gordon Loewen, PhD
FORUM Pharmaceuticals Inc.

Background: Despite treatment with antipsychotics, patients with schizophrenia have persistent cognitive deficits that adversely affect functioning and quality of life. Recent studies link reductions in α7 receptor (α7R) signaling to cognitive dysfunction in schizophrenia. Agents that potentiate α7R signaling may therefore enhance cognition and improve patient function. This Phase IIb study assessed the effects of encenicline, a novel α7R potentiator, on cognitive and clinical function in stable patients with chronic schizophrenia.

Methods: Subjects receiving stable antipsychotics were treated with placebo or encenicline (0.3 mg or 1 mg once daily) for 84 days. Efficacy was evaluated using the Overall Cognition Index (OCI) from the CogState testing battery and Trails 2 and 4 of the Neuropsychological Test Battery, the MATRICS Consensus Cognitive Battery (MCCB), the Schizophrenia Cognition Rating Scale (SCoRS), and the Positive and Negative Syndrome Scale (PANSS). P<0.10 was considered significant. Results: Encenicline was associated with significant improvement in cognitive function due mainly to improvements in visual learning, visual attention, and social cognition as measured by the OCI and MCCB. Significant improvements in clinical function were also observed with encenicline as measured by the SCoRS and PANSS. There were no clinically significant safety findings.

Conclusions: Encenicline treatment of patients with schizophrenia promoted clinically significant improvements in cognitive function. These results may have important implications for the clinical management of schizophrenia since cognitive symptoms predict functional outcomes, including employment, level of supportive living, and social functioning. Larger Phase III trials are ongoing.

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