scholarly journals Long-term safety and effectiveness of open-label lurasidone in antipsychotic-Naïve versus previously treated adolescents with Schizophrenia: A post-hoc analysis

2022 ◽  
Vol 240 ◽  
pp. 205-213
Author(s):  
Christoph U. Correll ◽  
Michael Tocco ◽  
Andrei Pikalov ◽  
Jay Hsu ◽  
Robert Goldman
Keyword(s):  
Open Label ◽  
Post Hoc Analysis ◽  
Previously Treated ◽  
Post Hoc

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 Efficacy of Lurasidone in Antipsychotic-Naive vs. Antipsychotic-Exposed Adolescents with Schizophrenia: Post-Hoc Analysis of a Two-Year, Open-Label Study

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 147-147
Author(s):  
Christoph Correll ◽  
Michael Tocco ◽  
Andrei Pikalov ◽  
Jay Hsu ◽  
Robert Goldman
Keyword(s):  
Effect Size ◽  
Extension Phase ◽  
Controlled Study ◽  
Open Label ◽  
Antipsychotic Therapy ◽  
Post Hoc Analysis ◽  
Long Term Treatment ◽  
Treatment Naïve ◽  
Post Hoc

AbstractBackgroundFew studies have examined treatment response in adolescents with schizophrenia who are treatment-naive; and there is no placebo-controlled study that we are aware of in first episode treatment-naive patients with schizophrenia. The aim of this analysis was to evaluate the long-term efficacy of lurasidone in antipsychotic-naive adolescents with schizophrenia.MethodPatients aged 13–17 years with schizophrenia, and a PANSS total score ≥70 and <120, were randomized to 6 weeks of double-blind (DB) treatment with lurasidone (40 or 80 mg/day) or placebo. Six-week completers were eligible to enroll in a 2-year open-label extension phase receiving lurasidone flexibly dosed from 20–80 mg/day. In a post-hoc analysis, efficacy was evaluated for 2 patient groups based on treatment status prior to entering the initial 6-week DB study (treatment naïve [TN] vs. treated previously [TP]). Treatment-naïve was defined as never having received antipsychotic treatment. Efficacy measures included the PANSS total score and the Clinical Global Impression, Severity (CGI-S) score. Level of functioning was assessed using the Children’s Global Assessment Scale (CGAS), with a score of 70 representing normative levels of functioning.ResultsA total of 50 TN and 221 TP patients completed the 6-week DB study and entered the extension study; and 30 (60.0%) TN and 126 (57.0%) TP patients completed 104 weeks. During the initial 6 weeks of DB treatment, mean change in PANSS total score at endpoint was greater for lurasidone vs. placebo in both the TN group (−25.0 vs. −14.4; P<0.02; effect size, 0.75), and in the TP group (−17.3 vs. −10.0; P<0.001; effect size, 0.45). During OL extension phase treatment with lurasidone, mean change from DB baseline in the PANSS total score for TN and TP patients, at week 52 was −32.6 (n=38) and −28.1 (n=151), respectively; and at week 104 was −33.6 (n=30) and −29.2 (n=126), respectively. Mean change from DB baseline in CGI-S score at both weeks 52 and 104 was −1.8 for TN patients and −1.5 for TP patients. At DB baseline mean CGAS scores indicated significant functional impairment in both the TN and TP patients (CGAS=48 and 43, respectively). During OL treatment with lurasidone, mean change (from DB baseline) in the CGAS score at Weeks 52 and 104, respectively, was +22.0 and +22.9 in TN patients, and +21.1 and +22.9 in TP patients. During OL treatment with lurasidone, mean observed change from DB baseline in the weight (in kg,) at Weeks 52 and 104, respectively, was +4.2 and +4.8 in TN patients, and +4.0 and +5.0 in TP patients. These weight increases are consistent with expected weight gains in adolescents during a 2-year period (based on CDC growth charts).ConclusionsIn this post-hoc analysis of a 2-year study, adolescents with schizophrenia who had received no previous antipsychotic therapy showed greater improvement compared to previously treated patients during both short- and long-term treatment with lurasidone.FundingSunovion Pharmaceuticals Inc.

scholarly journals Effect of dose adjustments on the efficacy and safety of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of an open-label, long-term extension study (ORAL Sequel)

2022 ◽  
Author(s):  
Ruediger B. Mueller ◽  
Hendrik Schulze-Koops ◽  
Daniel E. Furst ◽  
Stanley B.  Cohen ◽  
Kenneth Kwok ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Minimum Clinically Important Difference ◽  
Extension Study ◽  
Efficacy And Safety ◽  
Open Label ◽  
Post Hoc Analysis ◽  
Clinically Important Difference ◽  
Post Hoc ◽  
The Impact

Abstract Introduction/objectives We assess the impact of switching versus staying on the same tofacitinib dose on efficacy and safety in patients with rheumatoid arthritis (RA). Methods ORAL Sequel was an open-label, long-term extension study of patients with RA receiving tofacitinib 5 or 10 mg BID for up to 9.5 years. Tofacitinib doses could be switched during the study at investigator discretion. In this post hoc analysis, data from ORAL Sequel were stratified into four groups: 5 → 10 mg BID (Dose-up); 5 mg BID (Stay-on 5); 10 → 5 mg BID (Dose-down); and 10 mg BID (Stay-on 10). Efficacy assessments over 12 months included: change from baseline in 4-component Sisease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28), and DAS28 minimum clinically important difference, remission, and low disease activity (LDA) rates. Safety was assessed for the study duration. Results Generally, DAS28 improvements and minimum clinically important difference rates were significantly greater (p < 0.05) in Dose-up versus Stay-on 5 up to month 12. DAS28 remission rates were significantly greater in Dose-up versus Stay-on 5 at month 12. Change from baseline in DAS28 was similar in Dose-down and Stay-on 10. No significant differences in DAS28 LDA rates were observed between groups. Safety data were similar overall across the four groups. Conclusion In patients with RA receiving open-label tofacitinib, this analysis found that some benefited from increasing dose from 5 to 10 mg BID and did not find that reducing dose from 10 to 5 mg BID affected efficacy or that dose switching in either direction affected safety. Study registration ClinicalTrials.gov number NCT00413699. Registered December 20, 2006. https://clinicaltrials.gov/ct2/show/NCT00413699 Key Points• This post hoc analysis of data from the long-term extension study, ORAL Sequel, assessed the impact of dose switching between tofacitinib 5 and 10 mg twice daily (BID), at the investigator’s discretion, on efficacy and safety in patients with rheumatoid arthritis (RA).• Dosing up from tofacitinib 5 to 10 mg BID was associated with improved efficacy up to 12 months versus staying on 5 mg BID, and dosing down from 10 to 5 mg BID was not generally associated with a significant loss of efficacy.• Safety outcomes were generally consistent across dose groups and did not change markedly after switching dose in either direction.• These findings can help to inform physicians on what may be expected in terms of efficacy and safety when adjusting tofacitinib dose according to clinical need. The recommended tofacitinib dosage for the treatment of RA in most jurisdictions is 5 mg BID.

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.

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