[Translation] A randomized, open-label, single-dose, fasting, two-formulation, two-sequence, two-period crossover bioequivalence study of epalrestat tablets in healthy adult Chinese subjects

主要研究目的：单次口服50mg（空腹）受试制剂依帕司他片T（规格：50mg/片，湖南千金湘江药业股份有限公司生产）与参比制剂依帕司他片R（KINEDAK®，规格：50mg/片，小野药品工业株式会社生产），观察两种制剂在受试者体内的药代动力学特征，评估空腹状态下分别口服两种制剂的生物等效性次要研究目的：观察受试制剂T和参比制剂R单次口服50mg（空腹）在中国成年健康受试者中的安全性。

[Translation]

Main study objectives: A single oral administration of 50 mg (fasting) of the test preparation epalrestat tablets T (specification: 50 mg/tablet, produced by Hunan Qianjin Xiangjiang Pharmaceutical Co., Ltd.) and the reference preparation epalrestat tablets R (KINEDAK®, specification: 50 mg/tablet, produced by Ono Pharmaceutical Co., Ltd.) was conducted to observe the pharmacokinetic characteristics of the two preparations in the subjects and to evaluate the bioequivalence of the two preparations when taken orally in the fasting state Secondary study objectives: Observe the safety of a single oral administration of 50 mg (fasting) of the test preparation T and the reference preparation R in healthy adult Chinese subjects.

Start Date10 Sep 2024

Sponsor / Collaborator

Hunan Qianjin Xiangjiang Pharmaceutical Co., Ltd.

CTR20241582 / CompletedNot Applicable

依帕司他片在中国成年健康受试者中的一项随机、开放、空腹单次给药、两制剂、两序列、两周期交叉的生物等效性研究

[Translation] A randomized, open-label, single-dose, fasting, two-formulation, two-sequence, two-period crossover bioequivalence study of epalrestat tablets in healthy adult Chinese subjects

主要研究目的：考察空腹状态下单次口服1片受试制剂依帕司他片（规格：50 mg/片，海南赛立克药业有限公司生产，海南斯达制药有限公司提供）与参比制剂依帕司他片[商品名：KINEDAK，规格：50 mg/片，アルフレッサファーマ株式会社（Alfresa Pharma Corporation）生产，海南斯达制药有限公司提供]在中国成年健康受试者体内的相对生物利用度，分析两种制剂的药代动力学参数，评价两制剂的生物等效性。次要研究目的：评价空腹状态下单次口服1片受试制剂和参比制剂依帕司他片（规格：50 mg/片）在中国成年健康受试者中的安全性。

[Translation]

The main purpose of the study is to investigate the relative bioavailability of a single oral tablet of the test preparation epalrestat tablets (specification: 50 mg/tablet, produced by Hainan Celic Pharmaceutical Co., Ltd. and provided by Hainan Star Pharmaceutical Co., Ltd.) and the reference preparation epalrestat tablets [trade name: KINEDAK, specification: 50 mg/tablet, produced by Alfresa Pharma Corporation and provided by Hainan Star Pharmaceutical Co., Ltd.] in healthy adult Chinese subjects in the fasting state, analyze the pharmacokinetic parameters of the two preparations, and evaluate the bioequivalence of the two preparations. The secondary purpose of the study is to evaluate the safety of a single oral tablet of the test preparation and the reference preparation epalrestat tablets (specification: 50 mg/tablet) in healthy adult Chinese subjects in the fasting state.

Start Date28 Jun 2024

Sponsor / Collaborator

Hainan Star Pharmaceutical Co., Ltd.

CTR20242135 / CompletedNot Applicable

依帕司他片（50mg）在中国健康受试者中空腹给药条件下随机、开放、单剂量、两序列、两周期、双交叉生物等效性试验。

[Translation] A randomized, open-label, single-dose, two-sequence, two-period, double-crossover bioequivalence study of epalrestat tablets (50 mg) in healthy Chinese subjects under fasting conditions.

主要研究目的：按有关生物等效性试验的规定，选择アルフレッサファーマ株式会社为持证商的依帕司他片（商品名：KINEDAK；规格：50mg）为参比制剂，对广东九明制药有限公司生产并提供的受试制剂依帕司他片（规格：50mg）进行空腹给药人体生物等效性试验，比较受试制剂中药物的吸收速度和吸收程度与参比制剂的差异是否在可接受的范围内，评价两种制剂在空腹给药条件下的生物等效性。次要研究目的：观察健康受试者口服受试制剂依帕司他片（规格：50mg）和参比制剂依帕司他片（商品名：KINEDAK；规格：50mg）的安全性。

[Translation]

Main research purpose: According to the relevant provisions of bioequivalence test, epalrestat tablets (trade name: KINEDAK; specification: 50mg) of which Alfred Pharmaceuticals Co., Ltd. is the licensee was selected as the reference preparation, and the human bioequivalence test of fasting administration of the test preparation epalrestat tablets (specification: 50mg) produced and provided by Guangdong Jiuming Pharmaceutical Co., Ltd. was conducted to compare whether the absorption rate and degree of the drug in the test preparation were within the acceptable range with the reference preparation, and to evaluate the bioequivalence of the two preparations under fasting administration conditions. Secondary research purpose: To observe the safety of oral administration of the test preparation epalrestat tablets (specification: 50mg) and the reference preparation epalrestat tablets (trade name: KINEDAK; specification: 50mg) by healthy subjects.

Start Date26 Jun 2024

Sponsor / Collaborator

Guangdong Jiu Ming Pharmaceutical Co., Ltd.

100 Clinical Results associated with Epalrestat

100 Translational Medicine associated with Epalrestat

100 Patents (Medical) associated with Epalrestat

307

Literatures (Medical) associated with Epalrestat

01 Jan 2025·European Journal of Medicinal Chemistry

Rational design and synthesis of novel N-benzylindole-based epalrestat analogs as selective aldose reductase inhibitors: An unexpected discovery of a new glucose-lowering agent (AK-4) acting as a mitochondrial uncoupler

Article

Author: Petrou, Anthi ; Santi, Alice ; Stefek, Milan ; Kovacikova, Lucia ; Kousaxidis, Antonios ; Paoli, Paolo ; Nicolaou, Ioannis ; Genovese, Massimo

Diabetes mellitus is one of the most frequent metabolic diseases associated with hyperglycemia. Although antidiabetic drugs reduce hyperglycemia, diabetic patients suffer from abnormal fluctuations in blood glucose levels leading to the onset of long-term complications. Aldose reductase inhibitors are considered a promising strategy for regulating the occurrence of diabetic-specific comorbidities. So far, epalrestat is the only drug being approved in Asian countries. In this paper, we ground our research in discovering novel epalrestat analogs that prevent chronic complications and normalize hyperglycemia. Herein, we describe the rational design and synthesis of four novel 4-thiazolidinone acetic acid derivatives (AK-1-4) being evaluated for their efficacy against aldose reductase from rat lenses and their specificity over the homologous enzyme from rat kidneys. AK-1-4 were also tested against human recombinant protein tyrosine phosphatase 1B as a key target in insulin sensitization and towards the closely related T-cell-derived enzyme. Docking analyses suggested possible binding modes on examined targets. The promising inhibitory profile of AK-4 sparked our interest in exploring its effect on the insulin-receptor signaling pathway and its ability to stimulate glucose uptake under ex vivo conditions. We further investigated the ability of AK-4 to target mitochondria acting as an uncoupling agent and impairing mitochondrial membrane potential. Herein, we report for the first time a new glucose-lowering agent (AK-4) that can combine alleviation for chronic diabetic complications without off-target adverse effects and antihyperglycemic efficacy through controlled mitochondrial uncoupling activity. Pharmacokinetic and toxicity studies in silico revealed optimal properties of AK-4 for oral administration without potential side effects.

02 Dec 2024·Journal of Biomolecular Structure and Dynamics

Pharmacophore derived 3D-QSAR, molecular docking, and simulation studies of quinoxaline derivatives as ALR2 inhibitors

Article

Author: Kulkarni, Swanand ; Singh, Yogesh ; Thareja, Suresh ; Kumar, Niraj ; Singh, Satwinder

Aldose Reductase 2 (ALR2), a key enzyme of the polyol pathway, plays a crucial role in the pathogenesis of diabetic complications. Quinoxaline scaffold-based compounds have been identified as potential ALR2 inhibitors for the management of diabetic complications. In the present work, molecular dynamic simulation studies in conjugation with pharmacophore mapping and atom-based 3D-QSAR were performed on a dataset of 99 molecules in comparison with Epalrestat (reference) to mark the desirable structural features of quinoxaline analogs to generate a probable template for designing novel and effective ALR2 inhibitors. The most potent compound 81 was subjected to MD simulation studies and found to be stable, with better interactions with the binding pocket as compared to Epalrestat. The MM-GBSA and MM-PBSA calculations showed that compound 81 possessed binding free energies of -35.96 and -4.92 kcal/mol, respectively. Atom-based 3D-QSAR yielded various pharmacophoric features with excellent statistical measures, such as correlation coefficient (R² value), F-value (Fischer ratio), Q² value (cross-validated correlation coefficient), and Pearson's R-value for training and test sets. Furthermore, the pharmacophore mapping provided a five-point hypothesis (AADRR) and docking analysis revealed the active ligand-binding orientations on the active site's amino acid residues TYR 48, HIE 110, TRP 111, and TRP 219. The results of this study will help in designing potent inhibitors of ALR2 for the management of diabetic complications.Communicated by Ramaswamy H. Sarma.

01 Nov 2024·Drug Delivery and Translational Research

Oleogels for the ocular delivery of epalrestat: formulation, in vitro, in ovo, ex vivo and in vivo evaluation

Article

Author: Concheiro, Angel ; Kattar, Axel ; Alvarez-Lorenzo, Carmen ; Chauhan, Anuj ; Mudakavi, Rajeev ; Vivero-Lopez, Maria

AbstractThe ocular administration of lipophilic and labile drugs such as epalrestat, an aldose reductase inhibitor with potential for diabetic retinopathy treatment, demands the development of topical delivery systems capable of providing sufficient ocular bioavailability. The aim of this work was to develop non-aqueous oleogels based on soybean oil and gelators from natural and sustainable sources (ethyl cellulose, beeswax and cocoa butter) and to assess their reproducibility, safety and efficiency in epalrestat release and permeation both ex vivo and in vivo. Binary combinations of gelators at 10% w/w resulted in solid oleogels (oleorods), while single gelator oleogels at 5% w/w remained liquid at room temperature, with most of the oleogels displaying shear thinning behavior. The oleorods released up to 4 µg epalrestat per mg of oleorod in a sustained or burst pattern depending on the gelator (approx. 10% dose in 24 h). The HET-CAM assay indicated that oleogel formulations did not induce ocular irritation and were safe for topical ocular administration. Corneal and scleral ex vivo assays evidenced the permeation of epalrestat from the oleorods up to 4 and 2.5 µg/cm2 after six hours, respectively. Finally, the capacity of the developed oleogels to sustain release and provide significant amounts of epalrestat to the ocular tissues was demonstrated in vivo against aqueous-based niosomes and micelles formulations loaded with the same drug concentration. Overall, the gathered information provides valuable insights into the development of oleogels for ocular drug delivery, emphasizing their safety and controlled release capabilities, which have implications for the treatment of diabetic neuropathy and other ocular conditions.Graphical abstract

News (Medical) associated with Epalrestat

18 Mar 2024

·www.prnewswire.com

Phase III clinical trial of pediatric subjects with PMM2-CDG begins crossover to open label epalrestat

STURGIS, Mich., March 18, 2024 /PRNewswire/ -- Maggie's Pearl, a collaboration between Perlara, Maggie's Cure, and the Mayo Clinic, announced that the Phase III trial of oral epalrestat therapy in pediatric subjects with PMM2-CDG (formerly, Congenital Disorder of Glycosylation Type 1a) has been green-lighted to transition to open label. All study subjects on placebo may transition to open label epalrestat at their 15-month study visit. The principal investigator, study team, participants, and their families remain blinded to original treatment assignments until all subjects reach their 15-month visit. The crossover recommendation was unanimous among an independent three-member data monitoring committee, comprising two physician scientists with PMM2 expertise and a biostatistician. The DMC concluded the planned interim analysis and determined that the trial can proceed safely. They recommended that each study participant continue with their randomly assigned treatment until the 15-month visit, when they can transition to open label epalrestat. Administered by the Mayo Clinic, the clinical trial is a prospective, single-center, randomized, double-blind, placebo-controlled study. In December 2021, the Food and Drug Administration notified Maggie's Pearl that the Phase III clinical trial in 40 patients with PMM2-CDG could proceed. The trial recruited 38 study subjects and closed enrollment in November 2023. The first 29 participants will complete their 15-month visits over the next 2-3 months. PMM2-CDG (phosphomannomutase-2-congenital disorder of glycosylation) is caused by mutations in a gene that supplies the instructions for making the PMM2 enzyme. The enzyme is involved in a process called glycosylation, in which sugar chains are created, altered, and chemically attached to specific proteins to form glycoproteins. Those proteins are key to normal growth and function of tissues and organs. No approved treatment options exist for patients with PMM2-CDG. "The DMC recommendation to allow study participants to receive epalrestat upon completing 15 months of randomized treatment is very encouraging," said Ethan Perlstein, CEO of Maggie's Pearl. "We can't thank participating families enough. They are medical pioneers and an example for all rare disease communities of what is possible despite the hardships of a placebo-controlled study. We look forward to opening discussions with FDA in the coming months to make epalrestat widely available for all PMM2-CDG families." The primary study objective is to evaluate the safety and probable benefit of oral epalrestat therapy in pediatric subjects with PMM2-CDG. More at: clinicaltrials.gov/ct2/show/NCT04925960. About Maggie's Pearl : Established in August 2020, Maggie's Pearl LLC is a joint venture between Perlara, Maggie's Cure, and the Mayo Clinic to identify potential drug therapies to treat and improve the lives of PMM2-CDG patients. Maggie's Pearl was inspired by Maggie Carmichael, a 10-year-old girl from Sturgis, Michigan, who was diagnosed with PMM2-CDG at eight months of age. At that time, Maggie's parents were told there was no treatment for the rare, and potentially fatal, genetic disease. Globally, roughly 1,000 people are known to have PMM2-CDG. More at . CONTACT: Pete Johnson, [email protected] SOURCE Maggie's Pearl

Phase 3

09 Jan 2023

·www.prnewswire.com

Maggie's Pearl Initiates Phase III Clinical Trial for Treatment of Patients with PMM2-CDG

Phase III epalrestat clinical trial to evaluate safety, tolerability, and clinical and metabolic improvement of pediatric subjects with PMM2-CDG STURGIS, Mich., Jan. 9, 2023 /PRNewswire/ -- Maggie's Pearl, a joint venture between Perlara, Maggie's Cure, and the Mayo Clinic, has started a Phase III clinical treatment trial to evaluate safety, tolerability, and clinical and metabolic improvement of pediatric subjects with PMM2-CDG (formerly known as Congenital Disorder of Glycosylation Type 1a) on oral epalrestat therapy versus a placebo. Administered by the Mayo Clinic, the clinical trial is a prospective, single-center, randomized, double-blind, placebo-controlled study. Maggie's Pearl received Food and Drug Administration approval in December 2021 to begin the Phase III clinical trial in 40 patients with PMM2-CDG. Now, the study is actively recruiting, and the first two study subjects were dosed in December 2022. PMM2-CDG, or phosphomannomutase-2-congenital disorder of glycosylation — is caused by mutations in a gene that supplies the instructions for making the PMM2 enzyme, which is involved in a process known as glycosylation. In that process, sugar chains are created, altered, and chemically attached to specific proteins to form glycoproteins. Those proteins are key to normal growth and function of tissues and organs. "This trial is the culmination of five years of research attempting to identify a new treatment option for pediatric PMM2-CDG," said Ethan Perlstein, CEO of Maggie's Pearl. "The start of this trial is an inflection point in our research. If this study demonstrates epalrestat to be safe and effective, families could finally have a viable treatment option for children living with PMM2-CDG." The primary study objective is to evaluate the safety and probable benefit of oral epalrestat therapy in pediatric subjects with PMM2-CDG. Study outcomes include evaluating the metabolic improvement of pediatric subjects treated with oral epalrestat therapy compared to those receiving the placebo. Additional areas of evaluation are safety, clinical improvement, and pharmacokinetics (PK) of oral epalrestat therapy, as well as urine polyols, adverse events, laboratory data, and other measures. To learn more about the trial, visit: clinicaltrials.gov/ct2/show/NCT04925960. About Maggie's Pearl Established in August 2020, Maggie's Pearl LLC is a joint venture between Perlara, Maggie's Cure, and the Mayo Clinic to identify potential drug therapies to treat and improve the lives of PMM2-CDG patients. Maggie's Pearl was inspired by Maggie Carmichael, a nine-year-old girl from Sturgis, Michigan, who was diagnosed with PMM2-CDG at eight months of age. At the time of her diagnosis, Maggie's parents were told there was no treatment for their daughter's rare, and potentially fatal, genetic disease. There are roughly 1,000 people in the world known to have PMM2-CDG. To learn more about Maggie's Pearl, visit: . CONTACT: Pete Johnson, (415) 806 - 7060 SOURCE Maggie's Pearl

Phase 3

16 Mar 2015

·www.bioportfolio.com

Shandong Shanda Wit Science & Technology Co., Ltd. (000915) - Financial and Strategic SWOT Analysis Review

Recently added to the BioPortfolio report store, Shandong Shanda Wit Science & Technology Co., Ltd. (000915) - Financial and Strategic SWOT Analysis Review is a new report from GlobalData published on 2015-01-31. This 25-page report is available in PDF from $300. Summary Shandong Shanda Wit Science & Technology Co., Ltd., (Shandong Shanda) is a pharmaceutical company. The company develops and markets drugs, environmentally friendly products, information products and materials. Its pharmaceutical products include azithromycin particles, oral iron dextran, licorice zinc particles, compound calcium carbonate effervescent granules, vitamin ad drops, epalrestat tablets, tartrate tablets, glimepiride tablets and long hormone. Shandong Shanda offers pharma products in the form of tablets and granules. The company’s environmentally friendly products include deep disc filter, sulfuric acid dilution device, depth disc filter, chlorine dioxide generator and large chlorine dioxide preparation device. It markets products under brand names, such as Yi Gan Yan, Yi Heng and Erik, among others. Shandong Shanda is headquartered in Jinan, China. This comprehensive SWOT profile of Shandong Shanda Wit Science & Technology Co., Ltd. provides you an in-depth strategic analysis of the company’s businesses and operations. The profile has been compiled by GlobalData to bring to you a clear and an unbiased view of the company’s key strengths and weaknesses and the potential opportunities and threats. The profile helps you formulate strategies that augment your business by enabling you to understand your partners, customers and competitors better. This company report forms part of GlobalData’s ‘Profile on Demand’ service, covering over 50,000 of the world’s leading companies. Once purchased, GlobalData’s highly qualified team of company analysts will comprehensively research and author a full financial and strategic analysis of Shandong Shanda Wit Science & Technology Co., Ltd. including a detailed SWOT analysis, and deliver this direct to you in pdf format within two business days. (excluding weekends). The profile contains critical company information including*, - Business description – A detailed description of the company’s operations and business divisions. - Corporate strategy – Analyst’s summarization of the company’s business strategy. - SWOT Analysis – A detailed analysis of the company’s strengths, weakness, opportunities and threats. - Company history – Progression of key events associated with the company. - Major products and services – A list of major products, services and brands of the company. - Key competitors – A list of key competitors to the company. - Key employees – A list of the key executives of the company. - Executive biographies – A brief summary of the executives’ employment history. - Key operational heads – A list of personnel heading key departments/functions. - Important locations and subsidiaries – A list and contact details of key locations and subsidiaries of the company. - Key manufacturing facilities – A list of key manufacturing facilities of the company. - Detailed financial ratios for the past five years – The latest financial ratios derived from the annual financial statements published by the company with 5 years history. - Interim ratios for the last five interim periods – The latest financial ratios derived from the quarterly/semi-annual financial statements published by the company for 5 interims history. Table of Contents Section 1 - About the Company Shandong Shanda Wit Science & Technology Co., Ltd. - Key Information Shandong Shanda Wit Science & Technology Co., Ltd. - Overview Shandong Shanda Wit Science & Technology Co., Ltd. - Key Employees Shandong Shanda Wit Science & Technology Co., Ltd. - Key Employee Biographies Shandong Shanda Wit Science & Technology Co., Ltd. - Key Operational Heads Shandong Shanda Wit Science & Technology Co., Ltd. - Major Products and Services Shandong Shanda Wit Science & Technology Co., Ltd. - History Shandong Shanda Wit Science & Technology Co., Ltd. - Company Statement Shandong Shanda Wit Science & Technology Co., Ltd. - Locations And Subsidiaries Shandong Shanda Wit Science & Technology Co., Ltd. - Key Manufacturing facilities Head Office Other Locations & Subsidiaries Section 2 - Company Analysis Shandong Shanda Wit Science & Technology Co., Ltd. - Business Description Shandong Shanda Wit Science & Technology Co., Ltd. - Corporate Strategy Shandong Shanda Wit Science & Technology Co., Ltd. - SWOT Analysis SWOT Analysis - Overview Shandong Shanda Wit Science & Technology Co., Ltd. - Strengths Shandong Shanda Wit Science & Technology Co., Ltd. - Weaknesses Shandong Shanda Wit Science & Technology Co., Ltd. - Opportunities Shandong Shanda Wit Science & Technology Co., Ltd. - Threats Shandong Shanda Wit Science & Technology Co., Ltd. - Key Competitors Section 3 - Company Financial Performance Charts Shandong Shanda Wit Science & Technology Co., Ltd. - Financial Ratios Financial Ratios - Capital Market Ratios Financial Ratios - Annual Ratios Financial Ratios - Interim Ratios Financial Ratios - Ratio Charts Section 4 - Appendix Appendix Methodology Ratio Definitions About GlobalData Contact Us Disclaimer Note*: Some sections may be missing if data is unavailable for the company For more information open Shandong Shanda Wit Science & Technology Co., Ltd. (000915) - Financial and Strategic SWOT Analysis Review. SKU: GDPH207645FSA

Financial Statement

100 Deals associated with Epalrestat

External Link

KEGG	Wiki	ATC	Drug Bank
D01688	Epalrestat	A10B	DB15293

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetic Neuropathies	JP	Alfresa Pharma Corp.	21 Jan 1992

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