Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study
Abstract Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptors agonist, has demonstrated efficacy in the treatment of patients with an acute exacerbation of schizophrenia in a 4-week, double-blind, placebo-controlled study. The aim of this 26-week open-label extension...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-12-01
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| Series: | npj Schizophrenia |
| Online Access: | https://doi.org/10.1038/s41537-021-00190-z |
| _version_ | 1797427197548429312 |
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| author | Christoph U. Correll Kenneth S. Koblan Seth C. Hopkins Yan Li Heather Dworak Robert Goldman Antony Loebel |
| author_facet | Christoph U. Correll Kenneth S. Koblan Seth C. Hopkins Yan Li Heather Dworak Robert Goldman Antony Loebel |
| author_sort | Christoph U. Correll |
| collection | DOAJ |
| description | Abstract Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptors agonist, has demonstrated efficacy in the treatment of patients with an acute exacerbation of schizophrenia in a 4-week, double-blind, placebo-controlled study. The aim of this 26-week open-label extension study was to evaluate the safety and effectiveness of ulotaront (25/50/75 mg/d) in patients who completed the initial 4-week study. Of the 193 4-week completers, 157 patients (81.3%) continued into the open-label extension study; 66.9% were completers. Among all extension phase patients, treatment with ulotaront was associated with minimal changes in body weight (mean [SD] change from double-blind baseline: −0.3 [3.7] kg), cholesterol (median change, −2.0 mg/dL), triglycerides (median, −5.0 mg/dL), and prolactin (female, median, −3.4 ng/mL; male, median, −2.7 ng/mL). Movement disorder scales showed no extrapyramidal effects. Twenty-six weeks of extension phase treatment was associated with a mean (95% CI) observed change from open-label baseline in the PANSS total score of −22.6 (−25.6, −19.6; effect size, 1.46), and a mean (95% CI) change in the CGI-Severity score of −1.0 (−1.2, −0.8; effect size, 1.07). Long-term treatment with the TAAR1 agonist ulotaront, in the daily dose range of 25–75 mg, was characterized by a relatively high completion rate, an adverse event profile notable for the absence of extrapyramidal-related adverse effects, a low liability for adverse weight and metabolic effects, and no effect on prolactin levels. Additional studies are needed to further confirm the long-term efficacy and safety of ulotaront. |
| first_indexed | 2024-03-09T08:40:47Z |
| format | Article |
| id | doaj.art-4df301f738ad41ac8b6310a8ae1d5dbb |
| institution | Directory Open Access Journal |
| issn | 2334-265X |
| language | English |
| last_indexed | 2024-03-09T08:40:47Z |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Schizophrenia |
| spelling | doaj.art-4df301f738ad41ac8b6310a8ae1d5dbb2023-12-02T16:47:21ZengNature Portfolionpj Schizophrenia2334-265X2021-12-01711910.1038/s41537-021-00190-zSafety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension studyChristoph U. Correll0Kenneth S. Koblan1Seth C. Hopkins2Yan Li3Heather Dworak4Robert Goldman5Antony Loebel6Department of Psychiatry, The Zucker Hillside Hospital, Northwell HealthSunovion Pharmaceuticals Inc.Sunovion Pharmaceuticals Inc.Sunovion Pharmaceuticals Inc.Sunovion Pharmaceuticals Inc.Sunovion Pharmaceuticals Inc.Sunovion Pharmaceuticals Inc.Abstract Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptors agonist, has demonstrated efficacy in the treatment of patients with an acute exacerbation of schizophrenia in a 4-week, double-blind, placebo-controlled study. The aim of this 26-week open-label extension study was to evaluate the safety and effectiveness of ulotaront (25/50/75 mg/d) in patients who completed the initial 4-week study. Of the 193 4-week completers, 157 patients (81.3%) continued into the open-label extension study; 66.9% were completers. Among all extension phase patients, treatment with ulotaront was associated with minimal changes in body weight (mean [SD] change from double-blind baseline: −0.3 [3.7] kg), cholesterol (median change, −2.0 mg/dL), triglycerides (median, −5.0 mg/dL), and prolactin (female, median, −3.4 ng/mL; male, median, −2.7 ng/mL). Movement disorder scales showed no extrapyramidal effects. Twenty-six weeks of extension phase treatment was associated with a mean (95% CI) observed change from open-label baseline in the PANSS total score of −22.6 (−25.6, −19.6; effect size, 1.46), and a mean (95% CI) change in the CGI-Severity score of −1.0 (−1.2, −0.8; effect size, 1.07). Long-term treatment with the TAAR1 agonist ulotaront, in the daily dose range of 25–75 mg, was characterized by a relatively high completion rate, an adverse event profile notable for the absence of extrapyramidal-related adverse effects, a low liability for adverse weight and metabolic effects, and no effect on prolactin levels. Additional studies are needed to further confirm the long-term efficacy and safety of ulotaront.https://doi.org/10.1038/s41537-021-00190-z |
| spellingShingle | Christoph U. Correll Kenneth S. Koblan Seth C. Hopkins Yan Li Heather Dworak Robert Goldman Antony Loebel Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study npj Schizophrenia |
| title | Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study |
| title_full | Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study |
| title_fullStr | Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study |
| title_full_unstemmed | Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study |
| title_short | Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study |
| title_sort | safety and effectiveness of ulotaront sep 363856 in schizophrenia results of a 6 month open label extension study |
| url | https://doi.org/10.1038/s41537-021-00190-z |
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