[Translation] A randomized, open-label, two-sequence, two-formulation, two-period, double-crossover bioequivalence study of a single oral dose of benzbromarone (50 mg) in healthy Chinese subjects in the fed state

主要研究目的：研究餐后状态下单次口服受试制剂苯溴马隆胶囊（规格：50mg，昆山龙灯瑞迪制药有限公司生产）与参比制剂苯溴马隆片（URINORM®，规格：50mg，トーアエイヨー株式会社生产）在健康成年受试者体内的药代动力学，评价餐后状态口服两种制剂的生物等效性。次要研究目的：餐后状态下，研究单次口服受试制剂苯溴马隆胶囊和参比制剂苯溴马隆片（URINORM®）在健康成年受试者中的安全性。

[Translation]

Main study objectives: To study the pharmacokinetics of the test preparation benzbromarone capsule (specification: 50mg, produced by Kunshan Longdeng Ruidi Pharmaceutical Co., Ltd.) and the reference preparation benzbromarone tablet (URINORM®, specification: 50mg, produced by Toeiyo Co., Ltd.) in healthy adult subjects after a single oral administration in the fed state, and to evaluate the bioequivalence of the two preparations after oral administration in the fed state. Secondary study objectives: To study the safety of the test preparation benzbromarone capsule and the reference preparation benzbromarone tablet (URINORM®) in healthy adult subjects after a single oral administration in the fed state.

Start Date16 Feb 2022

Sponsor / Collaborator

Kunshan Rotam Reddy Pharmaceutical Co. Ltd.

CTR20213305 / CompletedNot Applicable

中国健康受试者在空腹状态下单次口服苯溴马隆（50mg）的随机、开放、两序列、两制剂、两周期、双交叉设计的生物等效性试验临床研究计划及研究方案

[Translation] A randomized, open, two-sequence, two-formulation, two-period, double-crossover bioequivalence study of a single oral dose of benzbromarone (50 mg) in healthy Chinese subjects in the fasting state Clinical research plan and research program

主要研究目的：研究空腹状态下单次口服受试制剂苯溴马隆胶囊（规格：50mg，昆山龙灯瑞迪制药有限公司生产）与参比制剂苯溴马隆片（URINORM®，规格：50mg，トーアエイヨー株式会社生产）在健康成年受试者体内的药代动力学，评价空腹状态口服两种制剂的生物等效性。次要研究目的：空腹状态下，研究单次口服受试制剂苯溴马隆胶囊和参比制剂苯溴马隆片（URINORM®）在健康成年受试者中的安全性。

[Translation]

Main study objectives: To study the pharmacokinetics of a single oral dose of the test preparation benzbromarone capsule (specification: 50 mg, produced by Kunshan Longdeng Ruidi Pharmaceutical Co., Ltd.) and the reference preparation benzbromarone tablets (URINORM®, specification: 50 mg, produced by Toeiyo Co., Ltd.) in healthy adult subjects under fasting conditions, and to evaluate the bioequivalence of the two preparations when taken orally under fasting conditions. Secondary study objectives: To study the safety of a single oral dose of the test preparation benzbromarone capsule and the reference preparation benzbromarone tablets (URINORM®) in healthy adult subjects under fasting conditions.

Start Date15 Feb 2022

Sponsor / Collaborator

Kunshan Rotam Reddy Pharmaceutical Co. Ltd.

100 Clinical Results associated with Benzbromarone

100 Translational Medicine associated with Benzbromarone

100 Patents (Medical) associated with Benzbromarone

651

Literatures (Medical) associated with Benzbromarone

01 Feb 2024·Current molecular medicine

Time- and Concentration-Dependent Stimulation of Oxidative Stress in Chondrocytes by Intracellular Soluble Urate

Article

Author: Zhang, Yun ; Zhang, Bingqing ; Han, Yingdong ; Han, Xinxin ; Cao, Yu ; Zeng, Xuejun ; Di, Hong ; Yin, Yue

Background::

Gout could result in irreversible bone erosion, and chondrocyte might be involved in the process. Increased soluble urate is the early stage of gout and is strongly oxidative.

Objective::

To explore the effect of intracellular urate on the oxidative status of chondrocytes

Methods::

A chondrocyte model was used. Serial concentrations of exogenous urate were incubated with chondrocytes for increasing amounts of time. Reactive oxygen species (ROS), oxidant, and anti-oxidant molecules were measured with biochemical assays, rt-PCR, and western blot. A urate transport inhibitor and oxidative inhibitors were used to confirm the effect of exogenous urate.

Results::

All concentrations of exogenous urate stimulated the production of ROS in a time- and concentration-dependent manner, as well as oxidant molecules, including hydrogen peroxide (H2O2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nitric oxide (NO) inducible nitric oxide synthase (iNOS), and these effects, could be inhibited by oxidant inhibitors. However, anti-oxidant molecules, including acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), ataxia-telangiectasia mutated (ATM), heme oxygenase-1 (HO-1), and the transcription factor nuclear factor erythroid 2 (NF-E2)-related (Nrf2), was decreased by high concentrations of exogenous urate after prolonged incubation, but not by low to medium concentrations of exogenous urate. By inhibiting soluble urate trafficking, benzbromarone significantly suppressed the effect of urate stimulus on the oxidant and anti-oxidant molecules.

Conclusion::

Intracellular soluble urate could regulate chondrocyte redox balance in a time and concentration-dependent manner, and would be a target for regulating and protecting chondrocyte function in the early gout stage.

25 Jan 2024·Blood

Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis

Article

Author: Khandelwal, Sanjay ; Zhang, Yang ; Delahunty, Martha ; Telen, Marilyn J ; Liang, Pengfei ; Strouse, John J ; Wan, Yui Chun S ; Dong, Ping ; Arepally, Gowthami M ; Francis, Samuel J ; Yang, Huanghe ; Lowry, Augustus J ; Ma, Shang

Abstract:

Cell-surface exposure of phosphatidylserine (PS) is essential for phagocytic clearance and blood clotting. Although a calcium-activated phospholipid scramblase (CaPLSase) has long been proposed to mediate PS exposure in red blood cells (RBCs), its identity, activation mechanism, and role in RBC biology and disease remain elusive. Here, we demonstrate that TMEM16F, the long-sought-after RBC CaPLSase, is activated by calcium influx through the mechanosensitive channel PIEZO1 in RBCs. PIEZO1-TMEM16F functional coupling is enhanced in RBCs from individuals with hereditary xerocytosis (HX), an RBC disorder caused by PIEZO1 gain-of-function channelopathy. Enhanced PIEZO1-TMEM16F coupling leads to an increased propensity to expose PS, which may serve as a key risk factor for HX clinical manifestations including anemia, splenomegaly, and postsplenectomy thrombosis. Spider toxin GsMTx-4 and antigout medication benzbromarone inhibit PIEZO1, preventing force-induced echinocytosis, hemolysis, and PS exposure in HX RBCs. Our study thus reveals an activation mechanism of TMEM16F CaPLSase and its pathophysiological function in HX, providing insights into potential treatment.

01 Jan 2024·Journal of ethnopharmacology

Preliminary study on the material basis and mechanism underlying uric acid reduction by Thlaspi arvense L.

Article

Author: Yang, Xuan ; Ke, Xiumei ; Yang, Rongping ; Hou, Chao ; Wang, Yunhong ; Wu, Tongxuan ; Zhou, YiFei

ETHNOPHARMACOLOGICAL RELEVANCE:

In the Tibetan region of China, Thlaspi arvense L. is utilized for the prevention and treatment of hyperuricemia (HUA). Thlaspi arvense has been shown to lower uric acid levels in HUA rats in preliminary studies. However, the active components and mechanisms that account for its therapeutic effects remain elusive.

AIM OF STUDY:

Network pharmacology, ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS), mRNA-sequencing, and quantitative reverse transcription PCR (RT-PCR) were used to investigate the active ingredients of Thlaspi arvense against HUA in rats and elucidate the underlying mechanisms in this study.

MATERIALS AND METHODS:

A HUA rat model was established by a combination of intraperitoneal injection of potassium oxonate and intragastric administration of yeast extract. In the control and model groups, gastric gavage was performed to administer a normal saline solution, 4.5 mg kg^-1 benzbromarone in the positive drug group, and 3.5 g kg^-1Thlaspi arvense in the Thlaspi arvense group. After which network pharmacology and UPLC-Q-TOF-MS were employed to explore the active ingredients underlying the lowering of uric acid in Thlaspi arvense. In addition, mRNA-sequencing, network pharmacology and RT-PCR were applied to uncover Thlaspi arvense's mechanism of uric acid reduction.

RESULTS:

The results showed that a two-week administration of the effective constituents of Thlaspi arvense led to a significant improvement in HUA rats, including lower serum levels of uric acid (UA), xanthine oxidase (XOD), creatinine (CREA), carbamide (UREA), aspartate aminotransferase (AST), alanine transaminase (ALT), and liver tissue activities of XOD, ADA, super (MDA). A network pharmacological analysis revealed 40 active compounds, including organic acids and flavonoids, that act on HUA therapeutic targets. These targets primarily focus on pathways related to uric acid metabolism modulation, such as XOD, SLC22A12, ABCG2, SLC22A8, and others, reducing HUA. The analysis of mRNA-sequencing as well as RT-PCR data from renal tissue demonstrated that the targets modulating uric acid metabolism were SLC22A8, SLC12A1, and SLC16A7.

CONCLUSION:

In summary, organic acids and flavonoids may be the active components in Thlaspi arvense that alleviate HUA. The principal mechanisms are as follows: inhibition of XOD activity in the serum to reduce uric acid production, regulation of renal reabsorption and secretion of uric acid to increase uric acid excretion, and alleviation of oxidative stress reaction to decrease systemic damage and, eventually, treatment of HUA.

News (Medical) associated with Benzbromarone

16 Oct 2023

·www.biospace.com

Atom Bioscience Raises $83M in a D-Round Financing to Support Global Pivotal Clinical Trials of ABP-671, a New Treatment for Chronic Gout

JIANGSU, China--(BUSINESS WIRE)-- Atom Bioscience (Jiangsu Atom Bioscience and Pharmaceutical Co., Ltd.), a clinical stage biotechnology company developing best-in-class treatments for inflammatory and metabolic diseases, announced today completion of a D-round financing of approximately $83 million (CNY 600 million) for completion of global pivotal clinical trials of ABP-671, its unique orally administered URAT1 inhibitor for chronic gout. The funds also will be used to advance to clinical stage the company’s innovative pipeline of drugs for inflammatory and metabolic diseases. This round of financing includes new and existing investors and was led by Kaitai Capital. Other investors include Fortune Capital, Huajin Investment, Unifortune and NNFE Investment. After this round of financing, Atom has raised a total of nearly $165 million. "We appreciate the support of every investment institution involved in the D-round financing and previous investors,” said Dr. William Dongfang Shi, CEO, Chairman and Founder of Atom Bioscience. “We are honored to have their trust as we strive to promote innovative best-in-class drugs benefiting gout patients worldwide.” Chronic gout is caused by long-term hyperuricemia (serum uric acid (sUA) > 7 mg/dL or 420 μmol/L). More than 50 million patients suffer from gout worldwide and nearly 10 million in the U.S. Globally, there are more than 200 million people with hyperuricemia. Aside from the acute painful flare-ups associated with gout, the disease seriously affects people's quality of life and can increase the probability of sudden cardiac death and kidney function injury. The performance of existing gout drugs is far from meeting clinical needs. The drugs have poor efficacy and pose serious safety issues, such as leading to kidney failure, sudden cardiac death, or severe liver toxicity. ABP-671 reduces sUA levels by inhibiting renal urate transporter 1 (URAT1), resulting in normal excretion of urate in urine. Its clinical primary endpoint is to reduce sUA to < 6 mg/dL (360 μmol/L) and in previous clinical trials ABP-671 has demonstrated good efficacy, safety and tolerability. In two Phase 2 clinical trials of ABP-671 at doses ranging from 1 mg to 12 mg once a day, ABP-671 at a dose of 1 mg had showed a substantial reduction of sUA. At doses of 6 mg and 8 mg, 100% of subjects achieved the primary clinical end point of < 6 mg/dL. Notably, 100% of subjects experienced sUA levels of < 5 mg/dL (300 μmol/L), and there were 57% and 87.5% of subjects with sUA levels < 4 mg/dL (240 μmol/L), respectively. Some subjects had sUA levels < 3 mg/dL (180 μmol/L). At a dose of 12 mg of ABP-671, 100% of the subjects achieved sUA levels < 4 mg/dL. The two studies showed efficacy of ABP-671 can be maintained up to 24 hours with once daily dosing, and there were no significant adverse effects (AEs) compared to the placebo group. Maintaining sUA levels of 5 mg/dL to 4 mg/dL in gout patients is recommended by many national gout treatment guidelines. At these levels gout tophi are re-dissolved, tophi size and quantity are reduced and eventually acute gout attacks are reduced. This is difficult for most market drugs to achieve. “In terms of safety, ABP-671 is well tolerated. Its adverse events of ABP-671 were mostly grade 1 (mild and generally not bothersome), and the incidence is comparable to that of the placebo group,” said Dr. Shi. “No severe adverse events have occurred with ABP-671 at the doses tested.” He also observed, “A Human Mass Balance study, which evaluates how drugs are absorbed, metabolized and excreted, showed that ABP-671 is mostly excreted in its original form and does not produce any similar metabolites seen with benzbromarone (a currently marketed drug for gout treatment) which causes severe liver toxicity.” Dr. Shi added, “All subjects taking ABP-671 had a significant decrease in their sUA levels, therefore, we also plan to investigate ABP-671 for the treatment of refractory gout. In addition, we submitted a Pre-IND application to the U.S. FDA in August for ABP-745, which is used to treat inflammation and acute gout. We expect to submit the IND application in the U.S. and China in November.” About Atom Bioscience Atom Bioscience (Jiangsu Atom Bioscience and Pharmaceutical Co. Ltd.) is a fast-growing innovative drug company, focused on development of best-in-class small molecule therapeutics for treatment of inflammatory and metabolic diseases. The company’s lead product, ABP-671, is in clinical development for treatment of chronic gout. Another small molecule ABP-745 has shown significant efficacy and good safety in animal models of anti-inflammation, and is expected to be in Phase 1 clinical trials soon. For more information, please visit: or atombp.us. View source version on businesswire.com: Contacts Business Development Contact: Roy J. Wu, MBA Sr. Vice President, Business Development Atom Bioscience and Pharmaceutical Co., Ltd Email: roy.wu@atombp.com Source: Atom Bioscience View this news release online at:

Clinical ResultPhase 2INDPhase 1

09 Oct 2023

·www.biospace.com

Atom Bioscience Doses First Patient in Phase 2b/3 Clinical Trial of a New Treatment for Chronic Gout

JIANGSU, China--(BUSINESS WIRE)-- Atom Bioscience (Jiangsu Atom Bioscience and Pharmaceutical Co., Ltd.), a clinical stage biotechnology company developing new treatments for inflammatory and metabolic diseases, announced today the first patient has been dosed in a Phase 2b/3 clinical trial of ABP-671, a novel orally administered URAT1 inhibitor, for the treatment of chronic gout. The multicenter, randomized, double-blind trial will enroll 580 patients worldwide, including the U.S. The results from Part 1 of the study are expected to be available in Q4/2024. Part 1 will evaluate the safety and efficacy of ABP-671 at different doses and regimens. Part 2 of the study will be a confirmatory study for dosing regimens of ABP-671 selected from Part 1. “Gout affects more than 50 million people worldwide and is on the rise in many countries,” said Atom Bioscience CEO, Chairman and Founder Dr. William Dongfang Shi. "The need for a safe and effective treatment has never been greater. We believe our unique, potent, orally-available drug, ABP-671, will be a better treatment option for patients as suggested by currently available safety and efficacy data.” ABP-671 works by reducing the abnormally high levels of serum uric acid (sUA) and increasing excretion of urate through urine. Gout is one of the most common types of inflammatory arthritis. It is caused by long-term hyperuricemia, an excessive concentration of serum uric acid (sUA) greater than 7 mg/dL (420 μmol/L). Gout seriously affects patients’ quality of life and is associated with other serious comorbidities, including kidney function injury, increasing the probability of sudden cardiac death. Existing drugs for treating chronic gout have poor efficacy and pose serious safety issues, such as leading to kidney failure, sudden cardiac death, or severe liver toxicity. In two Phase 2 clinical trials of ABP-671 at doses ranging from 1 mg to 12 mg once a day, ABP-671 at a dose of 1 mg had showed a substantial reduction of sUA. 100% of subjects with levels of sUA achieved the primary endpoint of < 6 mg/dL at doses of 6 mg and 8 mg. Notably, 100% of subjects also experienced sUA levels of < 5 mg/dL, and there were 57% and 87.5% of subjects with sUA levels < 4 mg/dL (240 μmol/L), respectively. Some subjects had sUA levels < 3 mg/dL (180 μmol/L). At a dose 12 mg of ABP-671, 100% of the subjects achieved sUA levels <4 mg/dL. The two studies showed that the efficacy of ABP-671 can be maintained up to 24 hours with once daily dosing, and there were no significant adverse events compared to the placebo group. “In terms of safety, ABP-671 is well tolerated. Its adverse events were mostly grade 1 (mild and generally not bothersome), and the incidence is comparable to that of the placebo group,” said Dr. Shi. “No severe adverse events have occurred with ABP-671 at the dose tested.” Dr. Shi also added, “A Human Mass Balance study, which evaluates how drugs are absorbed, metabolized and excreted, showed that ABP-671 is mostly excreted in its original form and does not produce any of similar metabolites seen with benzbromarone (a currently marketed drug for gout treatment) which causes severe liver toxicity.” Maintaining sUA levels of 5 mg/dL to 4 mg/dL in gout patients is recommended by many national gout treatment guidelines. At these levels gout tophi are re-dissolved, tophi size and quantity are reduced and eventually acute gout attacks are reduced. This is difficult for most market drugs to achieve. About Atom Bioscience Atom Bioscience (Jiangsu Atom Bioscience and Pharmaceutical Co. Ltd.) is a fast-growing innovative drug company, focused on development of best-in-class small molecule therapeutics for treatment of inflammatory and metabolic diseases. The company’s lead product, ABP-671, is in clinical development for treatment of chronic gout. Another small molecule ABP-745 has shown significant efficacy and good safety in animal models of anti-inflammation, and is expected to be in phase 1 clinical trials soon. For more information, please visit: or atombp.us. View source version on businesswire.com: Contacts Business Development Contact: Roy J. Wu, MBA Sr. Vice President, Business Development Atom Bioscience and Pharmaceutical Co., Ltd Email: roy.wu@atombp.com Phase 2b/3 clinical trial information: ( ; NCT05818085) Source: Atom Bioscience View this news release online at:

Clinical ResultPhase 2Phase 1

100 Deals associated with Benzbromarone

External Link

KEGG	Wiki	ATC	Drug Bank
D01056	Benzbromarone	M04AB03	DB12319

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Hyperuricemia	JP	Pfizer Japan, Inc.	04 Nov 1986
Gout	JP	TOA Eiyo Ltd.	01 Aug 1978
Hypertension	JP	TOA Eiyo Ltd.	01 Aug 1978

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EULAR2023	Not Applicable	Gout	98	Benzbromarone	zbrzclsqyq(wbrgzjjgka) = ygmffhslvk liwcmvwawh (vbjgqslsdw, 1.0) View more	-	31 May 2023
RBR-5wvg53s (ERS2022)	Phase 2	Pulmonary Cystic Fibrosis Adjuvant TMEM16A \| CFTR	9	Benzbromarone 100 mg/day	bslhefffet(cyajebctvb) = wrhxqpkdjy qhdoyimrfv (qfkhqzhery, 3 - 9)	Positive	04 Sep 2022
ESC2017	Not Applicable	Chronic Kidney Diseases	120	Urate lowing therapy (ULT) group	rnaphxikey(imunaxsfdr) = kodglxlygp fhypincddn (mwlfwolyxc ) View more	-	28 Aug 2017
				Control group	rnaphxikey(imunaxsfdr) = ahacytcpni fhypincddn (mwlfwolyxc ) View more
EULAR2010	Not Applicable	Gout PTX3	-	Benzbromarone	pfqujodtze(oeejctnqpy) = bzjayvgexu cafvkxhrlp (cearmuabva )	Positive	16 Jun 2010
				Allopurinol	pfqujodtze(oeejctnqpy) = pcdmipfveh cafvkxhrlp (cearmuabva )
EULAR2010	Not Applicable	Gout allantoin	-	Benzbromarone	luefxomcbw(aemonbpsbf) = ywdzdhjglf trneusqbme (nkeyyuypno, 3.5) View more	-	16 Jun 2010
				Benzbromarone	luefxomcbw(aemonbpsbf) = marnthlxro trneusqbme (nkeyyuypno, 2.3) View more
NCT00422318 (Pubmed \| Circ Heart Fail)	Phase 4	Heart Failure	82	Benzbromarone	izcxkvlayv(djnvqzcktg) = tzfcydwpqo ouqcgtikyj (gxaeixyfgh ) View more	-	01 Jan 2010
				Placebo	izcxkvlayv(djnvqzcktg) = ccjpmqwlyi ouqcgtikyj (gxaeixyfgh ) View more
EULAR2007	Not Applicable	Gout Second line	-	Allopurinol 300 mg	arxkhmatub(ldrbafmigr) = 10% stopped allopurinol because of adverse drug reactions sadidsfbyt (ppraxqqbht )	-	13 Jun 2007
EULAR2005	Not Applicable	First line	16	Benzbromarone 100-200 mg/day	gyztvqidvl(gxepnmqvhc) = yjjmquitng sngixbuwux (jvxbbqppyj, 8) View more	Positive	08 Jun 2005
				Allopurinol 100-300 mg/day	gyztvqidvl(gxepnmqvhc) = biltibrdpd sngixbuwux (jvxbbqppyj, 11) View more

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