scholarly journals 14 Long-term Efficacy of Brexpiprazole in Patients with Schizophrenia with Clinically Relevant Levels of Negative Symptoms

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 180-180
Author(s):  
Catherine Weiss ◽  
Peter Zhang ◽  
Ross A Baker ◽  
Mary Hobart ◽  
Nanco Hefting ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Extension Study ◽  
Short Term ◽  
Open Label ◽  
Term Study ◽  
Post Hoc Analysis ◽  
Long Term Study ◽  
Open Label Extension ◽  
Post Hoc

AbstractBackgroundEffective treatments for patients with high levels of negative symptoms of schizophrenia are lacking. Brexpiprazole is a serotonin–dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all with subnanomolar potency. Long-term treatment with brexpiprazole demonstrated broad efficacy across all five Marder factor groupings, including positive, negative, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. This post-hoc analysis of long-term effects of brexpiprazole in patients with clinically relevant levels of negative symptoms of schizophrenia is based on data from two similarly designed short-term, placebo-controlled studies (Vector; NCT01396421 or Beacon; NCT01393613) for the brexpiprazole-treated patients who continued into an open-label extension study (Zenith; NCT01397786).MethodsIn the short-term studies, patients with acute schizophrenia were randomly assigned to fixed once-daily doses of brexpiprazole 0.25mg (Vector), 1mg (Beacon), 2mg , 4mg or placebo for 6weeks. The long-term study was an open-label, 52-week (amended to 26weeks), safety extension study with flexible-dose (1–4mg/day) brexpiprazole. The post-hoc analyses were performed on brexpiprazole-treated patients from the short-term studies who continued into the long-term study, and who had clinically relevant negative symptoms, defined as PANSS Factor Score for Negative Symptoms (PANSS-FSNS; N1, N2, N3, N4, G7, G16) of ≥24, and score of ≥4 on at least two of three core negative symptom PANSS items at randomization in the parent study. The outcome of the analysis included change from baseline to up to 58weeks in PANSS-FSNS, PANSS Total, and PSP. Safety was also assessed.ResultsA total of 187 patients with clinically relevant levels of negative symptoms in the parent study rolled-over into the open-label extension study and were available for analysis. Eighty-three of these patients remained in the studies for 58weeks. Due to the study amendment, not all patients had the opportunity of complete 52weeks of open-label treatment. Baseline PANSS Total score was 104.4, while baseline PANSS-FSNS was 27.6 and baseline PSP Total score was 41.3. Mean change (SD) from baseline in PANSS-FSNS was –10.9 (5.0), and –44.2 (17.5) for PANSS Total score at Week 58. Change from baseline (SD) to Week 58 for PSP Total score was 24.8 (12.9) with improvement in all domains (socially useful activities, personal and social relationship, self-care, and disturbing and aggressive behaviors). The TEAEs reported ≥5% were schizophrenia (18.9%), insomnia (8.6%), weight increased (5.9%) and akathisia (5.9%).ConclusionThis post-hoc analysis suggests that brexpiprazole has long-term effectiveness on negative symptoms and functioning in patients with schizophrenia and clinically relevant levels of negative symptoms.Funding Acknowledgements: The study was funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S

scholarly journals Cardiometabolic Safety of Lumateperone (ITI−007): Post Hoc Analyses of Short-Term Randomized Trials and an Open-Label Long-Term Study in Schizophrenia

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 152-152
Author(s):  
John B. Edwards ◽  
Andrew Satlin ◽  
Suresh Durgam ◽  
Robert E. Davis ◽  
Richard Chen ◽  
...  
Keyword(s):  
Metabolic Effects ◽  
Short Term ◽  
Open Label ◽  
Term Study ◽  
Study Objective ◽  
Post Hoc Analysis ◽  
Long Term Study ◽  
Conversion Rates ◽  
Post Hoc

AbstractStudy ObjectiveCurrent treatments for schizophrenia are often associated with increased rates of metabolic syndrome (MetSy). MetSy is defined as meeting 3 of the following 5 criteria: waist circumference >40in (men) or >35in (women), triglycerides =150mg/dL, high density lipoprotein cholesterol (HDL) <40mg/dL (men) or <50mg/dL (women), systolic blood pressure (BP) =130mmHg or diastolic BP =85mmHg, fasting glucose =100mg/dL. Patients with MetSy have an elevated risk of developing type II diabetes and increased mortality due to cardiovascular disease. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA approved for the treatment of schizophrenia. This distinct pharmacological profile has been associated with favorable tolerability and a low risk of adverse metabolic effects in clinical trials. This post hoc analysis of 2 randomized, double-blind, placebo-controlled studies of patients with an acute exacerbation of schizophrenia compared rates of MetSy with lumateperone and risperidone. Data from an open-label long-term trial of lumateperone were also evaluated.MethodThe incidence and shift in MetSy were analyzed in data pooled from 2 short-term (4 or 6 week) placebo- and active-controlled (risperidone 4mg) studies of lumateperone 42mg (Studies 005 and 302). The pooled lumateperone data were compared with data for risperidone. Data from an open-label 1-year trial (Study 303) evaluated MetSy in patients with stable schizophrenia switched from prior antipsychotic (PA) treatment to lumateperone 42mg.ResultsIn the acute studies (n=256 lumateperone 42mg, n=255 risperidone 4mg), rates of MetSy were similar between groups at baseline (16% lumateperone, 19% risperidone). At the end of treatment (EOT), MetSy was less common with lumateperone than with risperidone (13% vs 25%). More lumateperone patients (46%) compared with risperidone (25%) patients improved from having MetSy at baseline to no longer meeting MetSy criteria at EOT. Conversely, more patients on risperidone than on lumateperone developed MetSy during treatment (13% vs 5%). Differences in MetSy conversion rates were driven by changes in triglycerides and glucose. In the long-term study (n=602 lumateperone 42mg), 33% of patients had MetSy at PA baseline. Thirty-six percent of patients (36%) with MetSy at PA baseline improved to no longer meeting criteria at EOT. Fewer than half that percentage shifted from not meeting MetSy criteria to having MetSy (15%).ConclusionsIn this post hoc analysis, lumateperone 42mg patients had reduced rates of MetSy compared with risperidone patients. In the long-term study, patients with MetSy on PA switched to lumateperone 42mg had a reduction in the risk of MetSy. These results suggest that lumateperone 42mg is a promising new treatment for schizophrenia with a favorable metabolic profile.FundingIntra-Cellular Therapies, Inc.

scholarly journals 63 Long-term Outcomes with Aripiprazole Lauroxil for the Treatment of Schizophrenia: A 2-Year, Phase 3, Multicenter Extension Study

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 208-209
Author(s):  
Peter J Weiden ◽  
Amy Claxton ◽  
Yangchun Du ◽  
John Lauriello
Keyword(s):  
Outcome Data ◽  
Extension Study ◽  
Phase 3 ◽  
Post Hoc Analysis ◽  
Long Term Study ◽  
Long Term Treatment ◽  
Scale Scores ◽  
Post Hoc

AbstractBackgroundOne of the challenges in schizophrenia long-term trials is that clinical outcomes are often confounded by covert nonadherence to prescribed oral antipsychotics. This is a post hoc analysis (>2 years) of the symptoms and illness trajectory of patients treated with the long-acting injectable (LAI) antipsychotic aripiprazole lauroxil (AL). As adherence to LAIs can be monitored, these data could assess outcome trajectories unaffected by medication discontinuations that may occur with oral antipsychotics.MethodsThe efficacy and safety of once-monthly AL (441 or 882mg) for the treatment of schizophrenia were previously demonstrated in a phase 3 trial, followed by a 52-week, long-term safety study of two AL doses (441 or 882mg once monthly; patients continuing from the phase 3 study remained on their fixed AL dose [NCT01626456]), after which patients could enroll in a second long-term extension study. Patients entering the second long-term study continued on their fixed AL dose, with a variable follow-up period of up to 128 additional weeks (NCT01895452). In this post hoc analysis, the extension studies were combined to provide continuous outcome data over 2 years’ follow-up. The 12-week assessment visit (rather than the first visit) in the first extension study was chosen as the baseline to account for patients entering this study with variable AL exposure histories (with/without prior AL exposure). We report on the trajectory of symptoms and illness severity for >2 years (up to 112weeks) after the 12-week visit using the Positive and Negative Syndrome Scale (PANSS) total and Clinical Global Impression–Severity (CGI-S) scale scores. Course of illness was measured as the difference in PANSS and CGI-S scale scores within dose groups from baseline to end of follow-up, analyzed using MMRM.ResultsOverall, 432/478 patients entering the initial 52-week study were included in the post hoc analysis. For the AL 441 and 882mg groups, respectively, baseline scores (mean±SD) were 59.91±16.25 and 56.27±12.89 (PANSS), and 2.99±0.97 and 2.79±0.79 (CGI-S scale). Approximately 49% of patients (211/432) remained for the entire 112-week follow-up. Over this period, the trajectory of PANSS scores improved significantly compared with baseline for both the 441 and 882mg groups, with changes from baseline (least squares mean±SE) of −5.46±0.92 (P<.0001) and −4.99±0.53 (P<.0001), respectively. CGI-S scale scores had similar improvement: changes from baseline of −0.32±0.07 (P<.0001) and −0.28±0.04 (P<.0001) for the AL 441 and 882mg groups, respectively. Overall, AL was well tolerated, with a safety profile over a 2-year follow-up that was consistent with the initial 52-week safety results.ConclusionThis post hoc analysis demonstrates the safety and continued therapeutic efficacy of long-term treatment with AL in patients with schizophrenia. There were no apparent dose differences in the trajectory of symptom changes over the course of a 2-year follow-up.Funding Acknowledgements: This study was funded by Alkermes, Inc.

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