Phase 2 Crossover, Randomized, Placebo-Controlled, Single-Blind, Repeat Dose Study in Post-Bariatric Hypoglycemia Subjects to Determine the Effect of Mizagliflozin on Adverse Events and Postprandial Glucose Excursions

This is a phase 2 crossover, randomized, placebo-controlled, single-blind, repeat dose study in PBH subjects to determine the effect of mizagliflozin on adverse events and postprandial glucose excursions.

Start Date23 Jun 2023

Sponsor / Collaborator

Vogenx, Inc.

NCT05541939

/ CompletedPhase 2

Phase 2 Randomized Single Ascending Dose Study in Post-Bariatric Hypoglycemia Subjects to Determine the Effect of Mizagliflozin Formulations on Postprandial Glucose and Insulin Levels

This clinical study will examine the safety and tolerability, as well as the effects of orally administered mizagliflozin on post prandial glucose and insulin levels in subjects diagnosed with post-bariatric hypoglycemia (PBH).

Start Date13 Sep 2022

Sponsor / Collaborator

Vogenx, Inc.

NCT02343978

/ CompletedPhase 2

Phase II, Randomized, Open-label Study of KWA-0711 Administrated Orally for 2 Weeks to Evaluate Its Safety and Efficacy in Patients With Chronic Constipation (CC)

The purpose of this study is to evaluate the safety and efficacy of KWA-0711 in Chronic Constipation (CC) patients.

Start Date26 Dec 2014

Sponsor / Collaborator

Kissei Pharmaceutical Co., Ltd.

100 Clinical Results associated with Mizagliflozin

100 Translational Medicine associated with Mizagliflozin

100 Patents (Medical) associated with Mizagliflozin

Literatures (Medical) associated with Mizagliflozin

01 Jan 2025·International Journal of Pharmaceutics

Multi-method coamorphous systems of lumefantrine with alpha ketoglutaric acid: Comprehensive characterization, biological evaluation and stability analysis

Article

Author: Mehra, Neelesh Kumar ; Pardhi, Ekta ; Dhiman, Vivek ; Golla, Vijaya Madhyanapu ; Khemchandani, Rahul ; Shaikh, Nadeem ; Khushwaha, Bhoopendra Singh ; Samanthula, Gananadhamu ; Godugu, Chandraiah ; Medtiya, Pravin ; Tomar, Devendra Singh ; Goud, Sridivya

The coamorphous systems (CAM) of lumefantrine (LMF) and alpha-ketoglutaric acid (KGA) were developed using three different methods to address the solubility and bioavailability limitations of LMF. Powder X-ray diffraction spectroscopy (PXRD) and the differential scanning calorimetry (DSC) confirmed the complete amorphization of the three CAM by the halo pattern and glass transition temperature (Tg), respectively. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance spectroscopy (NMR) results indicated that intermolecular interactions existed in the three CAM. Solid-state molecular dynamics simulations revealed the different intermolecular disordered environments present in all three CAM. Solubility analysis showed 14.73×, 12.8× and 9.81× improvement in the liquid-assisted grinding-based coamorphous system (CAM LAG), solvent evaporation-based coamorphous system (CAM SE) and quench-cool-based coamorphous system (CAM QC), respectively, compared to LMF crystalline (LMF CRY). In the in-vitro dissolution experiment 2.63-, 2.16- and 2.17-times increments were observed in CAM LAG, CAM SE and CAM QC compared to LMF CRY, respectively. In-vivo pharmacokinetics study revealed 10.86-, 9.24- and 8.46- folds increments in C_max of CAM LAG, CAM SE and CAM QC, respectively, compared to LMF CRY. All three CAM illustrated anti-cancer activity in the A549 lung cancer cell line. Molecular dynamics simulation of LMF and KGA with Epidermal growth factor receptor (EGFR), a target for lung cancer treatment, revealed good binding affinity and stability. Stability studies performed under accelerated storage (40°C/75% RH) and extreme environmental conditions indicated that all three CAM have good stability. Different methods based prepared CAM have shown different physicochemical properties, bioavailability and stability profiles. These findings suggest that LMF-KGA CAM effectively addresses the solubility and bioavailability challenges of LMF, potentially leading to better therapeutic outcomes in lung cancer treatment.

25 Nov 2024·Cardiovascular Research

Crucial role for sensory nerves and Na/H exchanger inhibition in dapagliflozin- and empagliflozin-induced arterial relaxation

Article

Author: Abbott, Geoffrey W ; Benítez-Angeles, Miguel ; Albert, Anthony P ; Barrese, Vincenzo ; Salles-Crawley, Isabelle ; Forrester, Elizabeth A ; Dora, Kim ; Greenwood, Iain A ; Rosenbaum, Tamara ; Dannesboe, Johs ; Jepps, Thomas A ; Redford, Kaitlyn E

AbstractAimsSodium/glucose transporter 2 (SGLT2 or SLC5A2) inhibitors lower blood glucose and are also approved treatments for heart failure independent of raised glucose. Various studies have showed that SGLT2 inhibitors relax arteries, but the underlying mechanisms are poorly understood and responses variable across arterial beds. We speculated that SGLT2 inhibitor-mediated arterial relaxation is dependent upon calcitonin gene-related peptide (CGRP) released from sensory nerves independent of glucose transport.Methods and resultsThe functional effects of SGLT1 and 2 inhibitors (mizagliflozin, dapagliflozin, and empagliflozin) and the sodium/hydrogen exchanger 1 (NHE1) blocker cariporide were determined on pre-contracted resistance arteries (mesenteric and cardiac septal arteries) as well as main renal conduit arteries from male Wistar rats using wire myography. SGLT2, CGRP, TRPV1, and NHE1 expression was determined by western blot and immunohistochemistry. Kv7.4/5/KCNE4 and TRPV1 currents were measured in the presence and absence of dapagliflozin and empagliflozin. All SGLT inhibitors (1–100 µM) and cariporide (30 µM) relaxed mesenteric arteries but had negligible effect on renal or septal arteries. Immunohistochemistry with TRPV1 and CGRP antibodies revealed a dense innervation of sensory nerves in mesenteric arteries that were absent in renal and septal arteries. Consistent with a greater sensory nerve component, the TRPV1 agonist capsaicin relaxed mesenteric arteries more effectively than renal or septal arteries. In mesenteric arteries, relaxations to dapagliflozin, empagliflozin, and cariporide were attenuated by the CGRP receptor antagonist BIBN-4096, depletion of sensory nerves with capsaicin, and blockade of TRPV1 or Kv7 channels. Neither dapagliflozin nor empagliflozin activated heterologously expressed TRPV1 channels or Kv7 channels directly. Sensory nerves also expressed NHE1 but not SGLT2 and cariporide pre-application as well as knockdown of NHE1 by translation stop morpholinos prevented the relaxant response to SGLT2 inhibitors.ConclusionSGLT2 inhibitors relax mesenteric arteries by promoting the release of CGRP from sensory nerves in a NHE1-dependent manner.

01 Oct 2023·Breast cancer research and treatment

SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.

Article

Author: Sasano, Hironobu ; Miki, Yasuhiro ; Onodera, Yoshiaki ; Suzuki, Takashi ; Kanai, Ayako ; Iwabuchi, Erina ; Tsunokake, Satoko ; Ishida, Takanori

PURPOSESodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained remain virtually unknown. Therefore, in this study, we explored the expression status of SGLT1 and SGLT2 in breast cancer patients and examined the effects of SGLT1 inhibitors on breast carcinoma cells in vitro.METHODSSGLT1 and SGLT2 were immunolocalized and we first correlated the findings with clinicopathological factors of the patients. We then administered mizagliflozin and KGA-2727, SGLT1 specific inhibitors to MCF-7 and MDA-MB-468 breast carcinoma cell lines, and their growth-inhibitory effects were examined. Protein arrays were then used to further explore their effects on the growth factors.RESULTSThe SGLT1 high group had significantly worse clinical outcome including both overall survival and disease-free survival than low group. SGLT2 status was not significantly correlated with clinical outcome of the patients. Both mizagliflozin and KGA-2727 inhibited the growth of breast cancer cell lines. Of particular interest, mizagliflozin inhibited the proliferation of MCF-7 cells, even under very low glucose conditions. Mizagliflozin downregulated vascular endothelial growth factor receptor 2 phosphorylation.CONCLUSIONHigh SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors.

News (Medical) associated with Mizagliflozin

22 Aug 2023

·www.prnewswire.com

Post-bariatric Hypoglycemia in the 7MM: Navigating the Challenges, Opportunities, and Emerging Therapies (2023-2032)

DUBLIN, Aug. 22, 2023 /PRNewswire/ -- The "Post-Bariatric Hypoglycemia Market Insights, Epidemiology and Forecast to 2032" report has been added to ResearchAndMarkets.com's offering. The postbariatric hypoglycemia landscape is marked by both challenges and opportunities. While the US dominates the market, gaps in diagnostic criteria and standardized treatments persist. Emerging therapies like mizagliflozin and AVEXITIDE hold promise in reshaping the treatment paradigm. Future efforts should focus on developing effective treatments tailored to individual needs, considering the variability in patients' responses to current therapies. As the field evolves, innovative solutions are expected to drive significant transformations in the postbariatric hypoglycemia market. Epidemiology and Market Trends In 2022, the United States contributed to about 79% of postbariatric hypoglycemia cases across the 7MM (United States, EU4 countries, and Japan). The US also dominated the market, constituting approximately 89% of the total 7MM market share. Nevertheless, due to the lack of standardized diagnostic criteria, research findings comparison, prevalence rate determination, and uniform treatment approaches remain challenging. The present management landscape involves off-label therapies, which show varying effectiveness. Hence, there's a need for targeted and efficient treatments. Market Dynamics and Players The report delves into the market's future growth potential, encompassing diagnosis rates, disease progression, and treatment guidelines. Furthermore, it comprehensively covers management techniques and emerging therapies, including profiles of late-stage and significant therapies that could reshape the market. Notable players in the postbariatric hypoglycemia treatment arena include Vogenx and Eiger Biopharmaceuticals. The market shares among countries indicate that the US, EU4, the UK, and Japan hold varying sizes, with the US leading significantly. Emerging Therapies The report spotlights two emerging therapies: Mizagliflozin (Vogenx): An orally administered SGLT1 inhibitor, mizagliflozin, targets elevated SGLT1 levels in the gut of postbariatric hypoglycemia patients. This inhibits excessive insulin secretion triggered by elevated blood glucose levels. The drug is in Phase II clinical development. AVEXITIDE (Eiger BioPharmaceuticals): AVEXITIDE is a peptide blocking GLP-1 receptors, curbing dysregulated insulin secretion and reducing fasting and postprandial hypoglycemia. It has earned breakthrough designation for postbariatric hypoglycemia treatment and is progressing towards Phase III trials. Epidemiology and Expert Insights The report offers a comprehensive epidemiological outlook, segregating data by specific bariatric surgery cases, severity-specific PBH cases, and total treated PBH cases. The forecast shows rising cases in the US, EU4, the UK, and Japan. Insights from Key Opinion Leaders (KOLs) and Subject Matter Experts (SMEs) across prestigious institutions worldwide contribute to a robust understanding of the current and emerging treatment patterns. Qualitative Analysis and Market Access Through techniques like SWOT analysis and Conjoint Analysis, the report assesses various facets, such as disease diagnosis, patient awareness, cost-effectiveness, and therapy accessibility. It also addresses market access and reimbursement issues, exploring factors influencing the entry of innovative treatments into the market. Reimbursement plays a pivotal role in determining the adoption of expensive new drugs. Key Topics Covered 1. Key Insights 2. Report Introduction 3. Postbariatric Hypoglycemia (PBH) Market Overview at a Glance 4. Executive Summary of Postbariatric Hypoglycemia 5. Disease Background and Overview 6. Methodology 7. Epidemiology and Patient Population 8. Patient Journey 9. Emerging Therapies 10. Postbariatric Hypoglycemia (PBH): Seven Major Market Analysis 11. KOL Views 12. SWOT Analysis 13. Unmet Needs 14. Market Access and Reimbursement 15. Appendix A selection of companies mentioned in this report includes: Vogenx Eiger BioPharmaceuticals For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

Phase 2Phase 3Breakthrough Therapy

100 Deals associated with Mizagliflozin

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypoglycemia	Phase 2	US	Vogenx, Inc.	13 Sep 2022
Gastroparesis	Phase 2	-	Vogenx, Inc.	-
Diabetes Mellitus, Type 2	Preclinical	JP	Sumitomo Pharma Co., Ltd.	31 Mar 2008
Chronic constipation	Discovery	JP	Kissei Pharmaceutical Co., Ltd.	09 Sep 2013
Chronic idiopathic constipation	Discovery	JP	Kissei Pharmaceutical Co., Ltd.	16 May 2012
Diabetes Mellitus, Type 2	Discovery	JP	Sumitomo Pharma Co., Ltd.	31 Mar 2008

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05721729 (VGX 001-012, Company_Website) Manual	Phase 2	Hypoglycemia	15	Mizagliflozin	jnykktqguz(ujxcfhtgre) = okswgthitk mqldbihhcb (qkdvuybczf ) Met View more	Positive	26 Jun 2024
				Placebo	jnykktqguz(ujxcfhtgre) = zvomuniqvw mqldbihhcb (qkdvuybczf ) Met
NCT05541939 (CTgov)	Phase 2	Hypoglycemia	9	Mizagliflozin (Treatment Arm A)	oganmoubav(gfaadaspoo) = wodbqxrhoc xayvvvelrz (nbmbspqdts, wxsznhvzto - hslxrnnljz) View more	-	25 Jun 2024
				Mizagliflozin (Treatment Arm B)	kqajeitetu(fhsaknwmcf) = jwsixycqwg scnttxmjsd (qiewavswfz, chghzyvbpf - vmiwdrbofz) View more

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