Novel trace amine associated receptor-1 agonist SEP-363856 has significant antipsychotic effects in patients with schizophrenia, according to results of a study presented at Psych Congress 2019, held October 3 to 6 in San Diego, California. There were no notable differences between treatment with SEP-363856 and placebo in terms of safety and tolerability.
The 4-week randomized placebo-controlled phase 2 trial (ClinicalTrials.gov Identifier: NCT02969382) included patients randomly assigned to receive either once-daily SEP-363856 in doses of 50 mg or 75 mg (n=120) or placebo (n=125). Individuals included in the study were aged 18 to 40 years and met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for schizophrenia since first diagnosis ≥6 months, had ≥2 prior hospitalizations, and experienced an acute exacerbation of psychotic symptoms. Primary and secondary efficacy end points were week 4 change in Positive and Negative Symptom Scale score, and Clinical Global Impressions-Severity and Brief Negative Symptom Scale scores, respectively.
At week 4, a total of 22.9% of patients received 50 mg/d of SEP-363856 and 77.1% received 75 mg/d; mean daily dose of SEP-363856 was 64.3 mg/d, and dosage was reduced from 75 mg/d to 50 mg/d in only 2.5% of patients (n=3). There was no significant difference in total discontinuation rates between SEP-363856 and placebo.
In the primary analysis, a significant decrease in mean Positive and Negative Symptom Scale total score for SEP-363856 compared with placebo at week 4 (-17.2 vs -9.7; P =.001) was observed. In addition, significant reductions of SEP-363856 were also observed on the Clinical Global Impressions-Severity and Brief Negative Symptom Scale scores.
Results also indicated discontinuation because of an adverse event in 9.2% of patients in the SEP-363856 group compared with 6.4% in the control group. Adverse events occurring with an incidence ≥2% for SEP-363856 compared with placebo included somnolence, agitation, nausea, diarrhea, and dyspepsia. No significant differences were observed at end point between groups in terms of effects of weight, total cholesterol, glucose, triglycerides, and prolactin levels.
Overall, treatment with SEP-363856 showed statistically and clinically significant improvements in schizophrenia symptoms, including severity. The safety and tolerability of SEP-363856 were similar to those of placebo, and as expected, there were no dopamine-related patterns of adverse effects because SEP-363856 is a non-dopamine binding agent.
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Disclosures: This study was supported by Sunovion Pharmaceuticals Inc. Please see the original reference for a full list of authors’ disclosures.
Koblan K, Hopkins S, Kent J, Cheng H, Goldman R, Loebel A. Efficacy and safety of SEP-363856, a novel psychotropic agent with a non-D2 mechanism of action, in the treatment of schizophrenia: a 4-week, randomized, placebo-controlled trial. Presented at: Psych Congress 2019; Oct 3-6, 2019; San Diego, CA. Poster 206.