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M205. LONG-TERM SAFETY OF LUMATEPERONE (ITI-007): METABOLIC EFFECTS IN A 1-YEAR STUDY

BACKGROUND: Standard of care (SOC) treatments for schizophrenia are often associated with a spectrum of metabolic adverse effects including weight gain and increased risk of diabetes, hyperlipidemia, and hypertension. Identifying new schizophrenia treatments with a favorable weight gain and metaboli...

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Autores principales: Satlin, Andrew, Durgam, Suresh, Vanover, Kimberly E, Davis, Robert E, Huo, Jason, Mates, Sharon, Correll, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234755/
http://dx.doi.org/10.1093/schbul/sbaa030.517
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author Satlin, Andrew
Durgam, Suresh
Vanover, Kimberly E
Davis, Robert E
Huo, Jason
Mates, Sharon
Correll, Christoph
author_facet Satlin, Andrew
Durgam, Suresh
Vanover, Kimberly E
Davis, Robert E
Huo, Jason
Mates, Sharon
Correll, Christoph
author_sort Satlin, Andrew
collection PubMed
description BACKGROUND: Standard of care (SOC) treatments for schizophrenia are often associated with a spectrum of metabolic adverse effects including weight gain and increased risk of diabetes, hyperlipidemia, and hypertension. Identifying new schizophrenia treatments with a favorable weight gain and metabolic side effect profile is important in reducing patient morbidity, mortality, and improving patient outcomes Lumateperone (lumateperone tosylate, ITI-007) is a mechanistically novel agent for the treatment of schizophrenia that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This distinct pharmacological profile may confer favorable tolerability with a low risk of adverse metabolic effects compared with SOC treatment. In 3 short-term trials in patients with acute exacerbation of schizophrenia, lumateperone was associated with minimal weight gain and few metabolic side effects. This analysis of a phase 3 open-label study evaluated the weight change and metabolic profile of lumateperone in patients with stable schizophrenia that were switched from SOC to lumateperone 42-mg treatment (ITI-007 60 mg) for up to 1 year. METHODS: The metabolic profile of lumateperone was evaluated in prospective and post hoc analyses of an open-label study (Study 303). This study comprised patients with stable schizophrenia that were switched from SOC treatment to lumateperone 42 mg for 1 year of treatment; the study is currently ongoing to evaluate patients with greater than 1-year lumateperone exposure. Change in weight and metabolic assessments were conducted in all patients who completed 1 year of treatment and in patients who were classified at baseline by body mass index (BMI) as overweight (BMI 25–30) or obese (BMI ≥30). RESULTS: In the 1-year open-label study, 602 patients received at least 1 dose of lumateperone 42 mg and were included in the safety population; 239 patients completed 1 year of treatment. Mean cholesterol (total and low-density lipoprotein [LDL]) significantly decreased from SOC baseline (total: −11.4 mg/dL, P<.001; LDL: −10.2 mg/dL, P<.001). Significant improvements in mean body weight from SOC baseline were observed during the 1-year lumateperone treatment (−2.1 kg, P<.001). Lumateperone treatment was also associated with significant reductions from SOC baseline in BMI (−0.67 kg/m2, P=.002) and waist circumference in both men (−3.21 cm, P<.001) and women (−3.28, P<.001). Potentially clinically significant (PCS; ≥7% change from baseline) weight loss occurred in 19% of the population. Similarly, a high percentage of obese (19%) and overweight patients (21%) showed PCS weight decrease from SOC baseline. Conversely, PCS weight gain was infrequent in all patients (5%) and in obese (4%) and overweight (3%) patients. Shift from overweight to normal BMI occurred in 28% of patients; shift in BMI from overweight to obese occurred in 4% of patients. Improvement in BMI from obese to overweight was observed in 21% of patients. DISCUSSION: In patients switched from SOC treatment, improved metabolic and weight parameters were observed following 1 year of treatment with lumateperone 42 mg. Marked improvements were seen in patients that were overweight or obese at SOC baseline. These results suggest that lumateperone 42 mg may be a promising new treatment for schizophrenia, with minimal metabolic risk.
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spelling pubmed-72347552020-05-23 M205. LONG-TERM SAFETY OF LUMATEPERONE (ITI-007): METABOLIC EFFECTS IN A 1-YEAR STUDY Satlin, Andrew Durgam, Suresh Vanover, Kimberly E Davis, Robert E Huo, Jason Mates, Sharon Correll, Christoph Schizophr Bull Poster Session II BACKGROUND: Standard of care (SOC) treatments for schizophrenia are often associated with a spectrum of metabolic adverse effects including weight gain and increased risk of diabetes, hyperlipidemia, and hypertension. Identifying new schizophrenia treatments with a favorable weight gain and metabolic side effect profile is important in reducing patient morbidity, mortality, and improving patient outcomes Lumateperone (lumateperone tosylate, ITI-007) is a mechanistically novel agent for the treatment of schizophrenia that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This distinct pharmacological profile may confer favorable tolerability with a low risk of adverse metabolic effects compared with SOC treatment. In 3 short-term trials in patients with acute exacerbation of schizophrenia, lumateperone was associated with minimal weight gain and few metabolic side effects. This analysis of a phase 3 open-label study evaluated the weight change and metabolic profile of lumateperone in patients with stable schizophrenia that were switched from SOC to lumateperone 42-mg treatment (ITI-007 60 mg) for up to 1 year. METHODS: The metabolic profile of lumateperone was evaluated in prospective and post hoc analyses of an open-label study (Study 303). This study comprised patients with stable schizophrenia that were switched from SOC treatment to lumateperone 42 mg for 1 year of treatment; the study is currently ongoing to evaluate patients with greater than 1-year lumateperone exposure. Change in weight and metabolic assessments were conducted in all patients who completed 1 year of treatment and in patients who were classified at baseline by body mass index (BMI) as overweight (BMI 25–30) or obese (BMI ≥30). RESULTS: In the 1-year open-label study, 602 patients received at least 1 dose of lumateperone 42 mg and were included in the safety population; 239 patients completed 1 year of treatment. Mean cholesterol (total and low-density lipoprotein [LDL]) significantly decreased from SOC baseline (total: −11.4 mg/dL, P<.001; LDL: −10.2 mg/dL, P<.001). Significant improvements in mean body weight from SOC baseline were observed during the 1-year lumateperone treatment (−2.1 kg, P<.001). Lumateperone treatment was also associated with significant reductions from SOC baseline in BMI (−0.67 kg/m2, P=.002) and waist circumference in both men (−3.21 cm, P<.001) and women (−3.28, P<.001). Potentially clinically significant (PCS; ≥7% change from baseline) weight loss occurred in 19% of the population. Similarly, a high percentage of obese (19%) and overweight patients (21%) showed PCS weight decrease from SOC baseline. Conversely, PCS weight gain was infrequent in all patients (5%) and in obese (4%) and overweight (3%) patients. Shift from overweight to normal BMI occurred in 28% of patients; shift in BMI from overweight to obese occurred in 4% of patients. Improvement in BMI from obese to overweight was observed in 21% of patients. DISCUSSION: In patients switched from SOC treatment, improved metabolic and weight parameters were observed following 1 year of treatment with lumateperone 42 mg. Marked improvements were seen in patients that were overweight or obese at SOC baseline. These results suggest that lumateperone 42 mg may be a promising new treatment for schizophrenia, with minimal metabolic risk. Oxford University Press 2020-05 2020-05-18 /pmc/articles/PMC7234755/ http://dx.doi.org/10.1093/schbul/sbaa030.517 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Poster Session II
Satlin, Andrew
Durgam, Suresh
Vanover, Kimberly E
Davis, Robert E
Huo, Jason
Mates, Sharon
Correll, Christoph
M205. LONG-TERM SAFETY OF LUMATEPERONE (ITI-007): METABOLIC EFFECTS IN A 1-YEAR STUDY
title M205. LONG-TERM SAFETY OF LUMATEPERONE (ITI-007): METABOLIC EFFECTS IN A 1-YEAR STUDY
title_full M205. LONG-TERM SAFETY OF LUMATEPERONE (ITI-007): METABOLIC EFFECTS IN A 1-YEAR STUDY
title_fullStr M205. LONG-TERM SAFETY OF LUMATEPERONE (ITI-007): METABOLIC EFFECTS IN A 1-YEAR STUDY
title_full_unstemmed M205. LONG-TERM SAFETY OF LUMATEPERONE (ITI-007): METABOLIC EFFECTS IN A 1-YEAR STUDY
title_short M205. LONG-TERM SAFETY OF LUMATEPERONE (ITI-007): METABOLIC EFFECTS IN A 1-YEAR STUDY
title_sort m205. long-term safety of lumateperone (iti-007): metabolic effects in a 1-year study
topic Poster Session II
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234755/
http://dx.doi.org/10.1093/schbul/sbaa030.517
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