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

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S214-S214
Author(s):  
Andrew Satlin ◽  
Suresh Durgam ◽  
Kimberly E Vanover ◽  
Robert E Davis ◽  
Jason Huo ◽  
...  
Keyword(s):  
Weight Gain ◽  
Metabolic Profile ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Standard Of Care ◽  
Metabolic Effects ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Increased Risk

Abstract 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.

scholarly journals Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 276
Author(s):  
Stefania Raimondo ◽  
Dragana Nikolic ◽  
Alice Conigliaro ◽  
Gianluca Giavaresi ◽  
Bruna Lo Sasso ◽  
...  
Keyword(s):  
Risk Factors ◽  
Healthy Subjects ◽  
Cardiometabolic Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Modifiable Risk Factors ◽  
Low Density Lipoprotein Cholesterol ◽  
Open Label ◽  
Open Label Study ◽  
Label Study

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patented plant-based product citraVes™, containing extracellular vesicles (EVs) from Citrus limon (L.) Osbeck juice, and to investigate its ability to modulate different CV risk factors in healthy subjects. A cohort of 20 healthy volunteers was recruited in a prospective open-label study. All participants received the supplement in a spray-dried formulation at a stable dose of 1000 mg/day for 3 months. Anthropometric and hematobiochemical parameters were analyzed at the baseline and after the follow-up period of 1 and 3 months. We observed that the supplement has an effect on two key factors of cardiometabolic risk in healthy subjects. A significant change in waist circumference was found in women after 4 (85.4 [79.9, 91.0] cm, p < 0.005) and 12 (85.0 [80.0, 90.0] cm, p < 0.0005) weeks, when compared to the baseline value (87.6 [81.7, 93.6] cm). No difference was found in men (baseline: 100.3 [95.4, 105.2] cm; 4 weeks: 102.0 [95.7, 108.3] cm; 12 weeks: 100.0 [95.3, 104.7] cm). The level of LDL-C was significantly lower at 12 weeks versus 4 weeks (p = 0.0064). Our study evaluated, for the first time, the effects of a natural product containing plant-derived EVs on modifiable risk factors in healthy volunteers. The results support the use of EV extracts to manage cardiometabolic risk factors successfully.

A 12-Month Randomized, Open-Label Study of the Metabolic Effects of Olanzapine and Risperidone in Psychotic Patients

2011 ◽  
Vol 72 (12) ◽  
pp. 1602-1610 ◽  
Author(s):  
Herbert Y. Meltzer ◽  
Stefania Bonaccorso ◽  
William V. Bobo ◽  
Yuejin Chen ◽  
Karuna Jayathilake
Keyword(s):  
Metabolic Effects ◽  
Open Label ◽  
Open Label Study ◽  
Label Study

P01-249-Weight change and metabolic effects of asenapine in placebo- or olanzapine-controlled studies

2011 ◽  
Vol 26 (S2) ◽  
pp. 250-250
Author(s):  
J. Zhao ◽  
P. Cazorla ◽  
J. Schoemaker ◽  
M. Mackle ◽  
J. Panagides ◽  
...  
Keyword(s):  
Weight Gain ◽  
Weight Change ◽  
Serum Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Metabolic Effects ◽  
Glucose Levels ◽  
Baseline Weight ◽  
Image Position ◽  
Post Hoc

IntroductionWeight change and metabolic effects of atypical antipsychotics vary considerably.ObjectiveAssess weight and metabolic effects of asenapine in adults.AimDemonstrate that asenapine marketed doses are well tolerated compared with placebo or olanzapine.MethodsData were from pooled asenapine trials that used placebo (1748 patients; duration: 1−6 wk) and/or olanzapine (3430 patients; duration, 3−>100 wk) controls. Asenapine doses were 5 or 10 mg BID (2–20 mg BID in 2 studies); olanzapine doses were 5–20 mg QD. Post hoc inferential analyses based on ANOVA assessed change from baseline weight, body mass index, and fasting lipid and glucose levels.ResultsTable 1 summarizes the results.[Change From Baseline Weight and Metabolic Paramete]DiscussionThese post hoc pooled analyses support published reports and suggest asenapine was associated with moderate weight gain and increased fasting triglyceride and glucose levels vs placebo, but lower propensity for weight gain or increased serum lipids (ie, triglycerides, low-density lipoprotein, and cholesterol) vs olanzapine.

scholarly journals Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination with Oseltamivir, in Adults with Coronavirus Disease 19 The IONIC Trial

2021 ◽  
Author(s):  
Kavi Sharma ◽  
Dr Lisa Berry ◽  
Dr Evangelos Vryonis ◽  
Dr Asad Ali ◽  
Dr Beatriz Lara ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Trial Design ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Therapeutic Effects ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Link Type ◽  
Discharge From Hospital

Background: Globally there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID 19). Repurposing existing medications may offer the best hope for treating COVID 19 patients to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase (DHODH) inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with Oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents.(13) The IONIC trial is a randomized control trial that will investigate whether time to clinical improvement in COVID 19 patients is improved following a 14 day course of IMU-838 + Oseltamivir versus Oseltamivir alone. Methods: IONIC trial is an open label study in which participants will be randomised 1:1 in two parallel arms; the intervention arm (IMU-838 + Oseltamivir) and control arm (Oseltamivir only). The primary outcome is time-to-clinical improvement; defined as the time from randomisation to: a 2-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by UHCW NHS Trust and funded by LifeArc. Discussion: The IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) [IONIC Intervention] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care. Trial Registration: The trial was registered with EudraCT (2020-001805-21) on 09.04.2020 and ISRCTN on 23.09.2020 (ISRCTN53038326) and Clinicaltrials.gov on 17.08.2020 (NCT04516915) Strengths and Limitations: This study is the first to recruit participants in the trial exploring the effectiveness of IMU-838 in COVID-19. In addition, we believe it is the only trial exploring the effectiveness of IMU-838 in combination with Oseltamivir (Tamiflu) in patients with moderate to severe COVID-19. However, to make the trial design flexible due to the on-going pandemic the trial is un-blinded.

scholarly journals Auxora Versus Standard of Care For The Treatment of Severe or Critical COVID-19 Pneumonia: Results From A Randomized Controlled Trial

2020 ◽  
Author(s):  
Joseph Miller ◽  
Charles Bruen ◽  
Michael Schnaus ◽  
Jeffrey Zhang ◽  
Sadia Ali ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Ordinal Scale ◽  
Controlled Study ◽  
Respiratory Complications ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Randomized Controlled ◽  
Crac Channel ◽  
The Impact

Abstract BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study. RESULTS: In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died in the 30 days after randomization. Among patients with severe COVID-19 pneumonia, median time to recovery with Auxora was five days versus 12 days with SOC; recovery rate ratio was 1.87 (95%CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction=32%; 95%CI, -0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2=101-200. CONCLUSIONS: Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study. Trial registration: ClinicalTrials.gov, NCT04345614. Submitted 7April2020 - https://clinicaltrials.gov/ct2/show/NCT04345614

Sign in / Sign up

Export Citation Format

Share Document