The investigators aim to determine, using a point-of-care randomized controlled trial design, if hemodialysis patients, who are randomized to metoprolol succinate (a dialyzable, beta-1 selective beta blocker), have an improved cardiovascular outcome compared to those randomized to carvedilol (a non-dialyzable, non-selective beta blocker with alpha-1 antagonist properties). The investigators will also examine intervention practices to identify components that best support engagement and sustainability.

Start Date15 May 2024

Sponsor / Collaborator

VA Office of Research and Development

CTR20240785 / Active, not recruitingNot Applicable

琥珀酸美托洛尔缓释胶囊(100 mg)健康人体生物等效性研究

[Translation] Bioequivalence study of metoprolol succinate sustained-release capsules (100 mg) in healthy humans

本研究以桂林华信制药有限公司研发的琥珀酸美托洛尔缓释胶囊（规格：100 mg（以酒石酸美托洛尔计））为受试制剂，按生物等效性研究的有关规定，以持证商为Sun Pharmaceutical Industries, Inc.，生产厂家为Ohm Laboratories Inc. 生产的琥珀酸美托洛尔缓释胶囊（规格：100 mg（以酒石酸美托洛尔计），商品名称：Kapspargo Sprinkle®）为参比制剂，评估受试制剂和参比制剂在空腹/餐后条件下给药后的生物等效性。次要目的：观察受试制剂琥珀酸美托洛尔缓释胶囊和参比制剂琥珀酸美托洛尔缓释胶囊（Kapspargo Sprinkle®）在健康受试者中的安全性。

[Translation]

This study uses metoprolol succinate sustained-release capsules (specification: 100 mg (based on metoprolol tartrate)) developed by Guilin Huaxin Pharmaceutical Co., Ltd. as the test preparation. According to the relevant regulations on bioequivalence studies, The licensee is Sun Pharmaceutical Industries, Inc., and the manufacturer is Ohm Laboratories Inc. Metoprolol succinate sustained-release capsules (specification: 100 mg (based on metoprolol tartrate)), trade name: Kapspargo Sprinkle ®) is a reference preparation to evaluate the bioequivalence of the test preparation and the reference preparation after administration under fasting/postprandial conditions. Secondary purpose: To observe the safety of the test preparation metoprolol succinate extended-release capsules and the reference preparation metoprolol succinate extended-release capsules (Kapspargo Sprinkle®) in healthy subjects.

Start Date08 Mar 2024

Sponsor / Collaborator

Guilin Huaxin Pharmacy Co. Ltd.

CTRI/2023/11/060062 / Not yet recruitingPhase 3

A Phase III, Randomized, Double Blind, Active Controlled, Prospective, Parallel Group, Comparative, Multicentric Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Dapagliflozin plus Metoprolol Succinate Extended Release Tablets Versus Metoprolol Succinate Extended Release Tablets in Patients with Heart Failure with Reduced Ejection Fraction (HFrEF). - NIL

Start Date01 Dec 2023

Sponsor / Collaborator

Exemed Pharmaceuticals

100 Clinical Results associated with Metoprolol Succinate

100 Translational Medicine associated with Metoprolol Succinate

100 Patents (Medical) associated with Metoprolol Succinate

620

Literatures (Medical) associated with Metoprolol Succinate

01 May 2024·Computers in Biology and Medicine

Early prediction of long hospital stay for Intensive Care units readmission patients using medication information

Article

Author: Zhang, Min ; Kuo, Tsung-Ting

OBJECTIVEPredicting Intensive Care Unit (ICU) Length of Stay (LOS) accurately can improve patient wellness, hospital operations, and the health system's financial status. This study focuses on predicting the prolonged ICU LOS (≥3 days) of the 2nd admission, utilizing short historical data (1st admission only) for early-stage prediction, as well as incorporating medication information.MATERIALS AND METHODSWe selected 18,572 ICU patients' records from the MIMIC-IV database for this study. We applied five machine learning classifiers: Logistic regression (LR), Random Forest (RF), Support Vector Machine (SVM), AdaBoost (AB) and XGBoost (XGB). We computed both the sum dose and the average dose for the medication and included them in our model.RESULTSThe performance of the RF model demonstrates the highest level of accuracy compared to other models, as indicated by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.716 and an Expected Calibration Error (ECE) of 0.023.DISCUSSIONThe calibration improved all five classifiers (LR, RF, SVC, AB, XGB) in terms of ECE. The most important two features for RF are the length of 1st admission and the patient's age when they visited the hospital. The most important medication features are Phytonadione and Metoprolol Succinate XL. Also, both the sum and the average dose for the medication features contributed to the prediction task.CONCLUSIONOur model showed the capability to predict the prolonged ICU LOS of the 2nd admission by utilizing the demographic, diagnosis, and medication information from the 1st admission. This method can potentially support the prevention of patient complications and enhance resource allocation in hospitals.

01 Apr 2024·Journal of Pharmacy Practice

Severe Hypotension With Concomitant Sodium-Glucose Co-Transporter-2 Inhibitor and Angiotensin Receptor-Neprilysin Inhibitor Therapy in a Patient With Heart Failure Reduced Ejection Fraction: A Case Report

Article

Author: Schumacher, Christine

Background: Large cardiovascular outcomes trials in individuals with heart failure, with and without diabetes, have demonstrated a significant risk reduction in the composite outcome of cardiovascular death or hospitalizations for heart failure with SGLT2 inhibitor therapy. These positive outcomes have led to the recommendation that SGLT2 inhibitors serve as backbone therapy in patients with heart failure reduced ejection fraction (HFrEF). To date, there has not been enough participants in clinical trials on concomitant SGLT2 inhibitor and angiotensin receptor-neprilysin inhibitor therapy to evaluate the benefits and risks of combination therapy with these two agents outside of smaller subgroup analyses. Case Summary: This case describes a Black female with diabetes meeting her glycemic targets and concomitant stable NYHA FC II HFrEF on guideline-directed medical therapy (GDMT) with sacubitril/valsartan, spironolactone and metoprolol succinate who developed severe hypotension and dehydration requiring hospitalization after initiation of SGLT2 inhibitor therapy. Practice Implications: This case report raises the question of whether those with type 2 diabetes, and/or those on background angiotensin receptor-neprilysin inhibitor therapy, who are euvolemic or sensitive to diuretic therapy should be started on lower dose dapagliflozin and titrated to 10 mg daily based on response. It also raises awareness to the potential increased diuretic effect produced with concomitant use of sacubitril/valsartan and dapagliflozin. Caution and education to mitigate the risk for volume depletion should be provided to those patients who are euvolemic and initiated on a SGLT2 inhibitor, regardless of their background diuretic and GDMT. Conclusion: Future research should focus on the benefits and safety considerations and provide education on how to best initiate and adjust SGLT2 inhibitors in the setting of sacubitril/valsartan use in diverse heart failure patient populations.

01 Apr 2024·Redox Biology

Reactive oxygen species generation by reverse electron transfer at mitochondrial complex I under simulated early reperfusion conditions

Article

Author: Clary, Hannah ; Brookes, Paul S ; Nadtochiy, Sergiy M ; Tabata Fukushima, Caio ; Dancil, Ian-Shika ; Shah, Nidhi

Ischemic tissues accumulate succinate, which is rapidly oxidized upon reperfusion, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. In isolated mitochondria with succinate as the sole metabolic substrate under non-phosphorylating conditions, 90 % of ROS generation is from reverse electron transfer (RET) at the Q site of respiratory complex I (Cx-I). Together, these observations suggest Cx-I RET is the source of pathologic ROS in reperfusion injury. However, numerous factors present in early reperfusion may impact Cx-I RET, including: (i) High [NADH]; (ii) High [lactate]; (iii) Mildly acidic pH; (iv) Defined ATP/ADP ratios; (v) Presence of the nucleosides adenosine and inosine; and (vi) Defined free [Ca²⁺]. Herein, experiments with mouse cardiac mitochondria revealed that under simulated early reperfusion conditions including these factors, total mitochondrial ROS generation was only 56 ± 17 % of that seen with succinate alone (mean ± 95 % confidence intervals). Of this ROS, only 52 ± 20 % was assignable to Cx-I RET. A further 14 ± 7 % could be assigned to complex III, with the remainder (34 ± 11 %) likely originating from other ROS sources upstream of the Cx-I Q site. Together, these data suggest the relative contribution of Cx-I RET ROS to reperfusion injury may be overestimated, and other ROS sources may contribute a significant fraction of ROS in early reperfusion.

News (Medical) associated with Metoprolol Succinate

23 Feb 2024

·www.businesswire.com

Venatorx and Melinta Provide Update on Status of U.S. New Drug Application for Cefepime-Taniborbactam

MALVERN, Pa. & PARSIPPANY, N.J.--( BUSINESS WIRE )--Venatorx Pharmaceuticals (Venatorx) and Melinta Therapeutics (Melinta) announced today that the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding the New Drug Application (NDA) for cefepime-taniborbactam, a beta-lactam/beta-lactamase inhibitor (BL/BLI) combination antibiotic under review as a potential treatment for adult patients with complicated urinary tract infections (cUTI), including acute pyelonephritis caused by susceptible gram-negative microorganisms. The CRL did not identify clinical safety or efficacy issues in the NDA, and the FDA did not request any new clinical trials to support the approval of cefepime-taniborbactam. The FDA requested additional chemistry, manufacturing, and controls (CMC) and related data about the drug, testing methods, and manufacturing process. “While we are disappointed with this setback, we maintain utmost confidence in cefepime-taniborbactam. We are already hard at work generating the additional requested CMC data, and we will continue to work closely with the FDA so that we can make this important new medicine available to patients as quickly as possible,” said Christopher J. Burns, Ph.D., Chief Executive Officer of Venatorx. Melinta Chief Executive Officer and President, Christine Ann Miller added, “We are committed to our plans of supporting the US commercialization of this drug, which we believe when approved, will offer healthcare providers an important therapy for adult patients suffering from complicated urinary tract infections including acute pyelonephritis caused by susceptible gram-negative microorganisms.” About Cefepime-Taniborbactam Cefepime-taniborbactam is an investigational intravenous (IV) beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotic combination being developed for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Cefepime, a fourth-generation cephalosporin, is a widely used beta-lactam (BL) antibiotic with more than two decades of proven safety and clinical utility against susceptible gram-negative and gram-positive bacteria. Taniborbactam is a beta-lactamase inhibitor (BLI) that, in combination with cefepime, is being studied as a potential treatment option for patients with serious bacterial infections caused by antibiotic resistant gram-negative bacteria, most notably Extended Spectrum Beta-lactamase (ESBL)-expressing Enterobacterales, carbapenem-resistant Enterobacterales (CRE), and multidrug-resistant (MDR) Pseudomonas aeruginosa (MDR-PA), which can include carbapenem-resistant P. aeruginosa (CRPA). Cefepime-taniborbactam has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration (FDA). Fast Track designation is designed to facilitate the development, and to expedite the review of drugs to treat serious conditions that do not have sufficient treatment options. QIDP designation provides certain incentives for the development of new antibiotics, including priority review, as well as a five-year regulatory exclusivity extension. QIDP was authorized under the Generating Antibiotic Incentives Now (GAIN) Act of 2012, as part of the FDA Safety and Innovation Act, to underscore the urgency in development of new antibiotics. About Gram-Negative Infections and Antimicrobial Resistance (AMR) In a recent report on AMR, the U.S. Centers for Disease Control and Prevention (CDC) reported rates of resistance have increased significantly in the U.S. among bacterial pathogens including those commonly causing cUTI, pyelonephritis, and bacteremia. The CDC also cited that there are more than 2.8 million AMR infections annually in the U.S., which are directly related to more than 35,000 deaths. [1] Between 2014 and 2019, an analysis of U.S. UTI patients determined that 4.4% of cases were carbapenem resistant (CR) and 24.5% of U.S. UTI patients were bacteremic with 1.7% of cases caused by a CR pathogen. Patients with CR infections had a significantly longer hospital length of stay (LOS), were less likely to be discharged home, had a higher readmission rate, and had greater LOS-associated charges than patients with carbapenem-susceptible infections. Additionally, patients with bacteremia (urosepsis) due to CR pathogens had a significantly higher rate of mortality than those with carbapenem susceptible pathogens. [2] Gram-negative bacteria have multiple AMR mechanisms that continue to adapt in response to increases in antibiotic usage. Carbapenems are broad-spectrum antibiotics that have been widely used to treat infections caused by multidrug-resistant gram-negative bacteria, including Enterobacterales. With the increased global use of carbapenems, CRE have emerged, which have limited treatment options and are associated with increased morbidity and mortality. Resistance to carbapenems among Enterobacterales is primarily achieved by production of carbapenemases, which are enzymes capable of hydrolyzing carbapenem antibiotics and most other beta-lactams and fall into two distinct families: serine beta-lactamases and metallo-beta-lactamases (MBLs). K lebsiella pneumoniae carbapenemase (KPC), a class-A serine beta-lactamase, is one of the most prevalent carbapenemases, and New Delhi MBL (NDM) and Verona Integron-encoded MBL (VIM) are common variants of MBLs identified in gram-negative infections due to Enterobacterales and P. aeruginosa. According to an IHMA surveillance study in 2018-2019 and a JMI U.S. Surveillance study from 2021, MBLs were the most commonly identified carbapenem resistance mechanism globally among Enterobacterales isolates, with ~16 to 18% of U.S. CRE isolates carrying MBLs. [3,4] While CRPA is also increasing in some geographies due to emergence of MBLs, MDR-PA, which may exhibit resistance to carbapenems, represents an increasing challenge for clinicians and their patients in the U.S. and globally due to the paucity of treatment options for this primarily hospital-associated pathogen. Especially outside the U.S., CRPA may carry carbapenemases including MBLs (i.e., VIM); however, non-carbapenemase resistance mechanisms (i.e., efflux pumps, porins) also contribute to the growing global resistance of MDR-PA and CRPA. [5] If AMR infections continue on this trajectory, it has been projected that an estimated 10 million people will die per year of resistant infections by 2050—a number that surpasses the projected annual number of deaths (8.2 million) caused by cancer—and the cumulative cost to the global economy could be as high as U.S. $100 trillion. [6] In the U.S., estimates have reached as high as U.S. $20 billion in excess direct healthcare costs, with an additional U.S. $35 billion associated with lost productivity. [7] By 2050, the world is at risk of losing up to 3.8% of its annual gross domestic product with an annual shortfall of up to U.S. $3.4 trillion by 2030, a figure on par with losses attributable to the 2008 global financial crisis. [8] The Infectious Disease Society of America (IDSA) maintains updated guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections online at https://www.idsociety.org/practice-guideline/amr-guidance/ . [9] For those patients who do not respond to current treatment, new antibiotic therapies are needed to combat AMR. About Complicated Urinary Tract Infections Complicated UTIs, which include pyelonephritis, are defined as urinary tract infections ascending from the bladder accompanied by local and systemic signs and symptoms, including fever, chills, malaise, flank pain, back pain, and/or costovertebral angle pain or tenderness, that usually occur in the presence of a functional or anatomical abnormality of the urinary tract or in the presence of catheterization. Bacteremia can arise secondary to infections like cUTI and can result in substantial morbidity and mortality. [1] Annually in U.S., it is estimated that more than 3 million cUTI patients will be diagnosed and require antibiotic therapy leading to over $6 billion in annualized 30-day costs. [10] About Venatorx Pharmaceuticals Venatorx is a private, late-stage clinical pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections. Venatorx’s lead program, cefepime-taniborbactam, is a clinical-stage antibiotic that completed a Phase 3 study in adults with complicated urinary tract infections (cUTI), including pyelonephritis. In October 2022, BARDA awarded a contract of up to $318M for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multi-drug resistant infections. Cefepime-taniborbactam is currently under review by the FDA for the treatment of cUTI, including acute pyelonephritis. Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam (formerly known as VNRX-7145), for the treatment of cUTI, including pyelonephritis, caused by certain bacteria in adult patients with limited treatment options; this product is completing Phase 1 and will advance directly to a global Phase 3 cUTI clinical trial. For more information about Venatorx and its anti-infectives portfolio, please visit www.venatorx.com . About Melinta Therapeutics LLC Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA ® (delafloxacin), KIMYRSA ® (oritavancin), MINOCIN ® (minocycline) for Injection, ORBACTIV ® (oritavancin), REZZAYO ® (rezafungin for injection), TOPROL-XL ® (metoprolol succinate) and VABOMERE ® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit www.melinta.com . Funding Partners and Collaborators for Cefepime-Taniborbactam This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract number HHSN272201300019C, and Wellcome Trust under Award No. 360G-Wellcome-101999/Z/13/Z, and has continued with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract numbers HHSO100201900007C and 75A50122C00080. In September 2018, Venatorx entered into an exclusive license agreement with Everest Medicines to support the development, registration, and commercialization of cefepime-taniborbactam in Greater China, South Korea, and select countries in Southeast Asia. Everest will be solely responsible for the commercialization of cefepime-taniborbactam in its territory and Venatorx will be eligible to receive royalties on net sales. In April 2020, Venatorx and the GARDP Foundation (GARDP) announced a collaboration to accelerate the development of, and access to, cefepime-taniborbactam for adult and pediatric populations. Venatorx has granted GARDP exclusive rights to distribute and sub-distribute cefepime-taniborbactam, once it is approved for clinical use, in low- and lower-middle-income countries. In November 2023, Venatorx and Melinta entered into an exclusive License Agreement to facilitate a strategic partnership in the U.S. to commercialize cefepime-taniborbactam, a beta-lactam / beta-lactamase inhibitor (BL/BLI) combination antibiotic being developed for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults. In December 2023, Venatorx entered into an agreement with Menarini Group, who acquired the exclusive rights to commercialize, upon approval of relevant health authorities, cefepime-taniborbactam in 96 countries in Europe, Latin America, Middle East, Turkey and North Africa and the Commonwealth of Independent States (CIS). References [1] Antibiotic Resistance Threats in the United States 2019, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. [2] Shields et al. Burden of illness in U.S. hospitals due to carbapenem-resistant gram-negative urinary tract infections in patients with or without bacteremia. BMC Infectious Diseases (2021) 21:572. [3] Estabrook et al. Epidemiology of Resistance Determinants Identified in Meropenem-Nonsusceptible Enterobacterales Collected as Part of a Global Surveillance Study, 2018 to 2019. Antimicrobial Agents and Chemotherapy; May 2023, Vol. 67, Issue 5 [4] Castanheira et al. Increase in the Occurrence of Carbapenem-Resistant Enterobacterales in United States Hospitals from 2019 to 2021 and Activity of Novel Beta-Lactams/Beta-Lactamase Inhibitor Combinations Against these Isolates, 2022 ID Week Abstract #664. Open Forum Infectious Diseases, Volume 9, Issue Supplement_2, December 2022, ofac492.716 [5] Jean S-S, Harnod D and Hsueh P-R (2022) Global Threat of Carbapenem Resistant Gram-Negative Bacteria. Front. Cell. Infect.Microbiol.12:823684. doi:10.3389/fcimb.2022.823684[6] O’Neill, J. ‘Tackling Drug-Resistant Infections Globally: Final Report and Recommendations’. Review on Antimicrobial Resistance. May 2016. [6] O’Neill, J. ‘Tackling Drug-Resistant Infections Globally: Final Report and Recommendations’. Review on Antimicrobial Resistance. May 2016. [7] Antibiotic Resistance Threats in the United States 2013, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. [8] World Bank. Final Report Drug Resistant Infections: A Threat to Our Economic Future. Mar 2017. [9] Infectious Disease Society of America maintains updated guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections posted online at https://www.idsociety.org/practice-guideline/amr-guidance/ accessed July 2023 [10] Carreno et al. Longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. Open Forum Infectious Diseases. 8 October 2019

Phase 3License out/inFast TrackQualified Infectious Disease ProductNDA

20 Feb 2024

·www.biospace.com

New England Journal of Medicine Publishes Positive Results of Cefepime-Taniborbactam from Phase 3 CERTAIN-1 Study of Patients with Complicated Urinary Tract Infection

Cefepime-Taniborbactam Superior to Meropenem for the Composite Efficacy Endpoint Composite Efficacy Sustained at Late Follow-up Visit Safety Pro with Meropenem MALVERN, Pa. & PARSIPPANY, N.J. & FLORENCE, Italy--(BUSINESS WIRE)-- Venatorx Pharmaceuticals, Melinta Therapeutics LLC (“Melinta”), and Menarini Group today announced that The New England Journal of Medicine (NEJM) published the results of the CERTAIN-1 Phase 3 clinical study of the investigational agent cefepime-taniborbactam for the treatment of adult patients with complicated urinary tract infections (cUTI) and acute pyelonephritis (AP), including those with bacteremia. The results showed that cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a similar safety pro meropenem. This press release features multimedia. View the full release here: “Gram-negative infections such as cUTI have become increasingly difficult to treat due to acquired bacterial resistance to multiple classes of antibiotics. Cefepime-taniborbactam has the potential to treat a broad range of patients with cUTI due to suspected or confirmed multidrug-resistant (MDR) pathogens including Enterobacterales and Pseudomonas aeruginosa,” said Paul C. McGovern, MD, Senior Vice President at Venatorx and co-author of the publication. “This Phase 3 study is the culmination of a long journey of discovery and development, and we look forward to progressing this agent through the next regulatory stages so that the drug may reach patients world-wide as expeditiously as possible.” Christine Ann Miller, President and Chief Executive Officer of Melinta Therapeutics added, “We are pleased to see these results published in the New England Journal of Medicine. We look forward to leveraging our experience in marketing infectious disease products and our established commercial infrastructure, especially within the hospital and acute care settings, to make cefepime-taniborbactam available to physicians and their patients with complicated urinary tract infections if approved.” “E.coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are largely involved in cUTI Gram-negative pathogens infections reaching nearly 75% in Europe. We believe that the NEJM published CERTAIN-1 Phase 3 data indicating cefepime-taniborbactam's superiority on the composite endpoint of microbiological and clinical response alongside its comparable safety pro meropenem provides useful insight as to its expected contribution, upon approval by relevant regulatory authorities, in the treatment of hospitalized patients with cUTI starting in Europe,” said Najy Alsayed, Global Therapeutic Area Head-Infectious Diseases at Menarini Group. About CERTAIN-1 CERTAIN-1 was a randomized, multicenter, double-blind, active-controlled, non-inferiority study of hospitalized patients (N=661) with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP), comparing cefepime-taniborbactam (2.5 g every 8 hours) to meropenem (1 g every 8 hours). The primary endpoint was the composite microbiologic and clinical response at the Test of Cure (TOC) visit (Day 19-23) in the microbiological intention-to-treat (microITT) population. The non-inferiority margin was -15% and there was a prespecified superiority analysis if non-inferiority was concluded. Efficacy Data Cefepime-taniborbactam met the prospectively defined non-inferiority primary endpoint of composite microbiologic and clinical response versus meropenem at the TOC visit (70.6% response rate for cefepime-taniborbactam versus 58.0% for meropenem). The prespecified superiority analysis at the TOC visit demonstrated that cefepime-taniborbactam was statistically superior to meropenem for the composite endpoint (response rate difference: 12.6% [95% confidence interval (CI): 3.1, 22.2]; p=0.009) and for the microbiologic endpoint (response rate difference: 11.7% [CI: 2.9, 21.0]); the clinical endpoint response rate difference was 4.5% [CI: -2.6, 12.6]. At the Late Follow-up (LFU) visit (Day 28-35), cefepime-taniborbactam demonstrated sustained statistical superiority to meropenem for the composite endpoint (63.8% response rate for cefepime-taniborbactam versus 51.7% for meropenem (response rate difference: 12.1% [CI: 2.2, 21.9]) and for the clinical response endpoint (response rate difference: 9.9% [CI: 1.5, 18.8); the microbiologic endpoint response rate difference was 7.7% [CI: -1.6, 17.3]. Additionally, cefepime-taniborbactam maintained a numerical advantage to meropenem against resistant pathogens: cefepime-resistant (71% response rate for cefepime-taniborbactam versus 53% for meropenem), ESBL-producing (71% response rate for cefepime-taniborbactam versus 55% for meropenem) and MDR (68% response rate for cefepime-taniborbactam versus 60% for meropenem). Safety Data Cefepime-taniborbactam demonstrated a safety pro with meropenem. Treatment-emergent adverse events occurred in 35.5% and 29.0% of cefepime-taniborbactam and meropenem treated patients respectively. Serious adverse events occurred in 2.0% of cefepime-taniborbactam patients and 1.8% of meropenem treated patients. The most frequently reported treatment-emergent adverse events were headache (6.1% with cefepime-taniborbactam versus 3.7% for meropenem), diarrhea (4.1% versus 2.3%), and constipation (3.2% versus 1.4%). Three percent of patients treated with cefepime-taniborbactam discontinued therapy due to a treatment-emergent adverse event versus 0.9% of patients treated with meropenem. The safety data for cefepime-taniborbactam was consistent with the historical safety data for cefepime. About Cefepime-Taniborbactam Cefepime-taniborbactam is an investigational agent that is a combination of cefepime, a fourth-generation cephalosporin, and the novel beta-lactamase inhibitor (BLI), taniborbactam, that exhibits broad coverage of both serine- and metallo-beta-lactamases. In combination with cefepime, taniborbactam is under development as a new treatment option for patients with serious bacterial infections caused by difficult-to-treat drug resistant gram-negative pathogens, including carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant or multidrug-resistant Pseudomonas aeruginosa (CRPA/MDR-PA). Funding Partners and Collaborators for Cefepime-Taniborbactam This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract number HHSN272201300019C, and Wellcome Trust under Award No. 360G-Wellcome-101999/Z/13/Z, and has continued with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract numbers HHSO100201900007C and 75A50122C00080. In September 2018, Venatorx entered into an exclusive license agreement with Everest Medicines to support the development, registration, and commercialization of cefepime-taniborbactam in Greater China, South Korea, and select countries in Southeast Asia. Everest will be solely responsible for the commercialization of cefepime-taniborbactam in its territory and Venatorx will be eligible to receive royalties on net sales. In April 2020, Venatorx and the GARDP Foundation (GARDP) announced a collaboration to accelerate the development of, and access to, cefepime-taniborbactam for adult and pediatric populations. Venatorx has granted GARDP exclusive rights to distribute and sub-distribute cefepime-taniborbactam, once it is approved for clinical use, in low- and lower-middle-income countries. In November 2023, Venatorx and Melinta entered into an exclusive License Agreement to facilitate a strategic partnership in the U.S. to commercialize cefepime-taniborbactam, a beta-lactam / beta-lactamase inhibitor (BL/BLI) combination antibiotic being developed for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults. In December 2023, Venatorx entered into an agreement with Menarini Group, who acquired the exclusive rights to commercialize, upon approval of relevant health authorities, cefepime-taniborbactam in 96 countries in Europe, Latin America, Middle East, Turkey and North Africa and the Commonwealth of Independent States (CIS). About Venatorx Pharmaceuticals Venatorx is a private, late-stage clinical pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections. Venatorx’s lead program, cefepime-taniborbactam, is a clinical-stage antibiotic that completed a Phase 3 study in adults with complicated urinary tract infections (cUTI), including pyelonephritis. In October 2022, BARDA awarded a contract of up to $318M for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multi-drug resistant infections. Cefepime-taniborbactam is currently under review by the FDA for the treatment of cUTI, including acute pyelonephritis. Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam (formerly known as VNRX-7145), for the treatment of cUTI, including pyelonephritis, caused by certain bacteria in adult patients with limited treatment options; this product is completing Phase 1 and will advance directly to a global Phase 3 cUTI clinical trial.. For more information about Venatorx and its anti-infectives portfolio, please visit . About Melinta Therapeutics LLC Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA® (delafloxacin), KIMYRSA® (oritavancin), MINOCIN® (minocycline) for Injection, ORBACTIV® (oritavancin), REZZAYO® (rezafungin for injection), TOPROL-XL® (metoprolol succinate) and VABOMERE® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit . About Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4.4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit .

Phase 3License out/inClinical ResultPhase 1

15 Feb 2024

·www.businesswire.com

GoodRx Now Offering 30 Common Heart Health Medications for Under $30

SANTA MONICA, Calif.--( BUSINESS WIRE )-- GoodRx , the leading destination for prescription savings in the U.S., today announced it is offering 30 of the most common heart health medications for under $30 at more than 70,000 pharmacies nationwide. 1 Cardiovascular disease is one of the most prominent conditions facing Americans, affecting nearly half of all U.S. adults. That’s why GoodRx is making it easier for all individuals, regardless of insurance status, to access savings on both generic and brand-name medications that mitigate the risk and impact of cardiovascular conditions such as coronary artery disease, high cholesterol, hypertension, and more. By helping people afford their prescriptions, GoodRx is improving health outcomes and reducing the overall strain on the healthcare system. GoodRx’s recent report - The GoodRx Effect - estimates that GoodRx has directly contributed to the prevention of at least 140,000 emergency room visits and 110,000 hospitalizations for major adverse cardiovascular events like heart attack and stroke. Save an average of 84% on common generic medications 2 The following is a sample list of common generic medications used to treat cardiovascular disease that are available for under $30 on GoodRx. MEDICATION LOWEST PRICE 3 AVG % SAVINGS 4 ACE Inhibitors Lisinopril (generic Prinivil and Zestril) $9.29 67% Enalapril (generic Epaned and Vasotec) $15.54 75% Beta Blockers Carvedilol (generic Coreg) $10.68 75% Metoprolol ER (generic Toprol XL) $11.15 74% Propranolol (generic Inderal) $10.96 71% Calcium Channel Blockers Amlodipine (generic Amvaz, Katerzia, and Norvasc) $9.15 80% Diltiazem ER (generic Cardizem CD) $13.43 74% Statins Atorvastatin (generic Lipitor) $10.10 83% Pravastatin (generic Pravachol) $14.53 74% Rosuvastatin (generic Crestor) $10.57 91% Access exclusive discounts and savings on brand-name drugs GoodRx offers incredible savings on brand-name medications that are often more costly and harder to obtain: MEDICATION SAVINGS* Entresto Pay as little as $10 for up to a 90-day supply Jardiance Pay as little as $10 per month Lodoco Pay as little as $30 for up to a 90-day supply Ozempic Pay as little as $25 per month Repatha Pay as little as $5 per month Soaanz Exclusive discount to save over 70% Toprol XL Exclusive discount to save up to 51% Xarelto Pay as little as $10 per fill *May require private or commercial insurance Learn more about cardiovascular disease from trusted doctors, pharmacists and health experts GoodRx Health is a go-to resource for understanding common heart conditions, risk factors, treatment options and associated savings. The GoodRx Heart Health Center provides credible, timely and actionable information to help people better manage their health. Each article is researched and written by a team of editorial experts, and clinical content is reviewed by a team of medical experts that includes physicians, pharmacists, and more. “Improving access to affordable medications is the most important thing we can do to improve Americans’ heart health. The second most important is ensuring access to helpful, accurate information,” said Karla Robinson, MD , Medical Editor at GoodRx. “Knowledge is power, so we create easy-to-understand content that people can actually use so they are better equipped to minimize the risk of disease, find affordable medications, stick to their treatment plans, and ultimately improve their overall health and wellbeing.” To find savings and trusted health information, download the GoodRx app or go to www.goodrx.com/hearthealth . About GoodRx GoodRx is the leading destination for prescription savings in the U.S. We offer consumers free access to transparent and lower prices for generic and brand medications, as well as comprehensive healthcare research and information. We also equip healthcare professionals with efficient ways to find and prescribe affordable medications. Since 2011, GoodRx has helped consumers save more than $65 billion and is one of the most downloaded medical apps over the past decade. GoodRx periodically posts information that may be important to investors on its investor relations website at https://investors.goodrx.com . We intend to use our website as a means of disclosing material nonpublic information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors and potential investors are encouraged to consult GoodRx’s website regularly for important information, in addition to following GoodRx’s press releases, filings with the Securities and Exchange Commission (the “SEC”) and public conference calls and webcasts. The information contained on, or that may be accessed through, GoodRx’s website is not incorporated by reference into, and is not a part of, this press release. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding consumer savings; the benefits of our offerings to consumers, the U.S. healthcare system and GoodRx; and GoodRx’s plans, expectations and objectives. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, risks relating to our ability to achieve broad market education and change consumer purchasing habits, changes in medication pricing and pricing structures, our reliance on a limited number of industry participants, the competitive nature of our industry, risks related to government regulation of the internet, e-commerce, consumer data and privacy, information technology and cyber-security and the important factors discussed in the section entitled “Risk Factors” in GoodRx’s Annual Report on Form 10-K for the year ended December 31, 2022, as updated by our Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, and our other filings with the Securities and Exchange Commission. These factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. 1 Prices are subject to change at any time without notice. Prices may vary at different pharmacies, and for different forms, dosages, and quantities. 2 Calculated based on the difference between the average list price at a particular pharmacy and the average price paid by GoodRx consumers utilizing a GoodRx code at that same pharmacy in December 2023. 3 As of February 1, 2024. 4 Calculated based on the difference between the average list price at a particular pharmacy and the average price paid by GoodRx consumers utilizing a GoodRx code at that same pharmacy in December 2023.

AHA

100 Deals associated with Metoprolol Succinate

External Link

KEGG	Wiki	ATC	Drug Bank
D00635	Metoprolol Succinate	C07AB02	DB00264

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Angina Pectoris	CN	AstraZeneca Pharmaceuticals Co., Ltd.	-
Arrhythmias, Cardiac	CN	AstraZeneca Pharmaceuticals Co., Ltd.	-
Heart Failure	CN	AstraZeneca Pharmaceuticals Co., Ltd.	-
Hypertension	CN	AstraZeneca Pharmaceuticals Co., Ltd.	-
Hyperthyroidism	CN	AstraZeneca Pharmaceuticals Co., Ltd.	-
Neurocirculatory Asthenia	CN	AstraZeneca Pharmaceuticals Co., Ltd.	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fasting	Phase 1	IN	Ipca Laboratories Ltd.	01 Feb 2013
Hypertension	Discovery	DO	AstraZeneca PLC	01 Jul 2002

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESC2018	Not Applicable	-	80	Nebivolol 5 mg	(bppfdznaqt) = jslmysxzdz ymqfeueain (jzfarmywqn ) View more	-	27 Aug 2018
				Metoprolol succinate 50-100 mg	(bppfdznaqt) = yzftqpqzeu ymqfeueain (jzfarmywqn )
NCT01501929 (Pubmed)	Phase 4	Hypertension	25	Nebivolol	pgowizdues(efnboeygid) = jeprujazae zfsncyhpms (syccgqekyw ) View more	-	01 Jul 2016
				Metoprolol succinate	pgowizdues(efnboeygid) = evqaceupus zfsncyhpms (syccgqekyw ) View more
NCT02587351 (CTgov)	Phase 3	Pulmonary Disease, Chronic Obstructive	532	Metoprolol succinate (Metoprolol Succinate)	wldwzhqqnx(jahmnucnuq) = xewudnifll zljjkdaywa (nxxgrkbmya, vedtvbbvhx - nuddpovbox) View more	-	25 Jan 2021
				Placebo (Placebo)	wldwzhqqnx(jahmnucnuq) = zojsurepjm zljjkdaywa (nxxgrkbmya, fhfhxawjdx - bumqksrvgs) View more
NCT03488719 (CTgov)	Phase 1	-	37	Metoprolol Succinate 100 MG (Cohort 1 (Tesofensine 0.25mg))	zvtfntpsdg(oxiwdilmqz) = qsaruzrqmw juedqykwir (ivfljcqbrb, fyiymdhanz - pxfynqbizj) View more	-	09 Feb 2024
				Metoprolol Succinate 100 MG (Cohort 2 (Tesofensine 0.50mg))	zvtfntpsdg(oxiwdilmqz) = yzebvmwxco juedqykwir (ivfljcqbrb, vcjecjqrce - efqyttdjgt) View more
NCT01798992 (CTgov)	Phase 4	Cardiomyopathy, Dilated	56	Metoprolol succinate (Metoprolol Succinate)	(yguthvwsnm) = ubqystthwf unmyfkttte (pfnpzkvmew, siyyjnffbo - kedjwcosie) View more	-	20 Feb 2017
				doxazosin+Metoprolol succinate (Metoprolol Succinate + Doxazosin)	(yguthvwsnm) = ofsaqwausp unmyfkttte (pfnpzkvmew, dyhpgwmnen - mmjamaywjp) View more
NCT01501929 (CTgov)	Phase 4	Hypertension	32	Microvascular perfusion assessment using Definity+Nebivolol+Metoprolol succinate (Initial Treatment With Metoprolol)	bvjedaaybh(qvbordyrqu) = ypmyhdkxcl fatprdsmxg (bdepgkydmj, rgihswtnqg - rnslkqdlkw) View more	-	06 Nov 2018
				Microvascular perfusion assessment using Definity+Nebivolol+Metoprolol succinate (Initial Treatment With Nebivolol)	bvjedaaybh(qvbordyrqu) = ccqsbohxsh fatprdsmxg (bdepgkydmj, vxvweitknq - dnwcjagnkj) View more
NCT00756236 (CTgov)	Not Applicable	Myocardial Ischemia	60	Metoprolol (M-Group)	ajdbudrbrn(aykhywnkfm) = oqbmnbttpu txbqcfvtag (dheeryybyt, lyeyvtutsi - fczqdbrcue) View more	-	28 Jun 2017
				Esmolol (E-Group)	ajdbudrbrn(aykhywnkfm) = sjsfsbtkdj txbqcfvtag (dheeryybyt, uzmtabpdwo - giudtprarr) View more
NCT00995072 (CTgov)	Not Applicable	Female sexual dysfunction \| Hypertension	29	Nebivolol (Nebivolol 5 mg Daily)	prvfiyrkgn(esinyxdbqv) = ccyuuljokf oqtplaxfyq (qazccjpuyr, asfpygdsac - yxnpijobdz) View more	-	29 Mar 2019
				Metoprolol Succinate+Metoprolol (Metoprolol Succinate 100 mg Daily)	prvfiyrkgn(esinyxdbqv) = hnrgphrbhn oqtplaxfyq (qazccjpuyr, mpzzqljnsb - swbcxpgpqu) View more
NCT02293096 (CTgov)	Not Applicable	Hypertension	462	Metoprolol Succinate	rltjsurvjl(fdxqktxttv) = sdgtgkdpun thygtswxkz (gwjyrmvfge, xjedxfskpu - daudmnnyuf) View more	-	16 Sep 2021
NCT01658657 (CTgov)	Not Applicable	Hypertension	17	Lisinopril+metoprolol+Hydrochlorothiazide+Amlodipine (PRA-guided Therapy)	(wiahtvjcbv) = kaawjfpkye mvlxomokjt (gxvadynrpw, tfasptjelk - hqdgwpxjdc) View more	-	22 Jun 2015
				metoprolol+Amlodipine+lisinopril/hydrochlorothiazide (Fixed-dose Combination Treatment-guided Therapy)	(wiahtvjcbv) = nuurizsjhv mvlxomokjt (gxvadynrpw, ujgxkbxxxv - vcvmypdqyp) View more

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