Delving into the Latest Updates on Hyzetimibe with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

海泽麦布, 赛斯美

Target

NPC1L1

Mechanism

NPC1L1 inhibitors(Niemann-Pick C1-like protein 1 inhibitors), Cholesterol absorption inhibitors

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Primary hypercholesterolemia

Inactive Indication

AtherosclerosisCoronary Disease

Originator Organization

Zhejiang Hisun Pharmaceutical Co., Ltd.

Active Organization

Zhejiang Hisun Pharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (25 Jun 2021),

Primary hypercholesterolemia

RegulationSpecial Review Project (CN), Priority Review (CN)

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Structure

Molecular FormulaC25H21F2NO3

InChIKeyHEHHPZYUXSFAPV-GLGQCLCGSA-N

CAS Registry1266548-75-7

本试验旨在研究浙江海正药业股份有限公司研制、生产的海博麦布片（20 mg）在重度肾功能不全和健康受试者的药代动力学特征；观察海博麦布片（20 mg）在重度肾功能不全和健康受试者中的安全性；为肾功能不全患者的临床用药提供依据。

[Translation]

This study aims to study the pharmacokinetic characteristics of Hebomib tablets (20 mg) developed and produced by Zhejiang Hisun Pharmaceutical Co., Ltd. in severe renal insufficiency and healthy subjects; to observe the safety of Hebomib tablets (20 mg) in severe renal insufficiency and healthy subjects; and to provide a basis for clinical medication in patients with renal insufficiency.

Start Date29 Aug 2023

Sponsor / Collaborator

Zhejiang Hisun Pharmaceutical Co., Ltd.

CTR20232181 / CompletedPhase 4

评估海博麦布片在肝功能不全和健康受试者中的多中心、非随机、开放、平行对照的药代动力学研究

[Translation] A multicenter, non-randomized, open-label, parallel-controlled pharmacokinetic study to evaluate the efficacy of Hebomib tablets in subjects with hepatic impairment and healthy subjects

主要研究目的：评价海博麦布片单次给药后，在不同程度肝功能不全和健康受试者中的药代动力学特征，评估不同程度肝功能不全对药物药代动力学（PK）的影响，为肝功能不全患者的临床用药提供依据。次要研究目的：评价海博麦布片单次给药后，在不同程度肝功能不全和健康受试者中的安全性。

[Translation]

Main study objectives: To evaluate the pharmacokinetic characteristics of Hebomib tablets in subjects with different degrees of hepatic insufficiency and healthy subjects after a single administration, to assess the effects of different degrees of hepatic insufficiency on drug pharmacokinetics (PK), and to provide a basis for clinical medication in patients with hepatic insufficiency. Secondary study objectives: To evaluate the safety of Hebomib tablets in subjects with different degrees of hepatic insufficiency and healthy subjects after a single administration.

Start Date23 Aug 2023

Sponsor / Collaborator

Zhejiang Hisun Pharmaceutical Co., Ltd.

CTR20231843 / CompletedNot Applicable

海博麦布片和非诺贝特胶囊在健康受试者中的药物相互作用研究

[Translation] Study on drug interaction between Hebomib tablets and fenofibrate capsules in healthy subjects

主要目的：评价健康受试者口服海博麦布片和非诺贝特胶囊的药物代谢动力学相互作用。次要目的：评价健康受试者口服海博麦布片和非诺贝特胶囊的安全性和耐受性。

[Translation]

Primary objective: To evaluate the pharmacokinetic interaction of oral Hebomib tablets and fenofibrate capsules in healthy subjects. Secondary objective: To evaluate the safety and tolerability of oral Hebomib tablets and fenofibrate capsules in healthy subjects.

Start Date25 Jun 2023

Sponsor / Collaborator

Zhejiang Hisun Pharmaceutical Co., Ltd.

100 Clinical Results associated with Hyzetimibe

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100 Translational Medicine associated with Hyzetimibe

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100 Patents (Medical) associated with Hyzetimibe

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6

Literatures (Medical) associated with Hyzetimibe

01 Nov 2023·European Journal of Pharmaceutical Sciences

Physiologically based pharmacokinetic modeling to characterize enterohepatic recirculation and predict food effect on the pharmacokinetics of hyzetimibe

Article

Author: Jiang, Bo ; Ruan, Zourong ; Shao, Rong ; Chen, Jinliang ; Yang, Dandan ; Chen, Wenjun ; Lou, Honggang

BACKGROUND AND OBJECTIVEHyzetimibe is a cholesterol absorption inhibitor indicated for the treatment of hypercholesterolemia. This study aims to describe the multiple-peak pharmacokinetics (PK) of hyzetimibe and its active metabolite M1 through physiologically-based pharmacokinetic (PBPK) modeling, and to compare the model predictions of a virtual food effect study with the results of a clinical food effect study.METHODSThe plasma concentration data used for PBPK modeling were obtained from a single-dose, two-period crossover bioequivalence study in the fasted state. Advanced Compartmental Absorption and Transit model was used for absorption. Enterohepatic recirculation process was modeled by changing the gut physiological state from fasted to fed at meal time. Based on the established PBPK models, a virtual food effect study was simulated. A clinical food effect study was used for model external validation.RESULTSPK profiles of hyzetimibe and M1 under fasting condition could be well described by the PBPK model, and the errors of C_max, AUC_0-∞, and AUC_0-t were within the two-fold range. Simulated geometric mean ratios (GMRs, fed/fasted) showed that a high-fat breakfast slightly affected the PK of hyzetimibe, expressed as increased C_max of hyzetimibe (130.6%). Simulated GMRs and 90% confidence intervals of AUC were within the preset bioequivalent range. The results of the simulated virtual food effect trial were consistent with those of the clinical food effect trial.CONCLUSIONSThe established PBPK model could describe the concentration-time profiles of hyzetimibe and M1 well with good prediction performance. A fully mechanistic model of enterohepatic recirculation warrants further investigation.

01 Jul 2022·British Journal of Clinical PharmacologyQ2 · MEDICINE

Population pharmacokinetics and enterohepatic recirculation of hyzetimibe and its main metabolite in Chinese healthy subjects

Q2 · MEDICINE

Article

Author: Jiang, Bo ; Ruan, Zourong ; Shao, Rong ; Lou, Honggang ; Yang, Dandan ; Chen, Jinliang ; Chen, Wenjun

AimsHyzetimibe (HS‐25), a new drug approved for hypercholesterolaemia, exhibits obvious enterohepatic recirculation (EHC) after oral administration. Up to now, little is known about the kinetics of HS‐25. Therefore, we performed this population pharmacokinetic (PopPK) analysis aiming to describe the PK behaviour of HS‐25 and its main metabolite (M1), and to identify significant covariates contributing to the variability.MethodsThe plasma concentration data used for modelling were obtained from an open‐label, single‐dose, randomized, 2‐period crossover bioequivalence study. PopPK modelling was performed with NONMEM 7.4.1 using nonlinear mixed effect modelling approach. Goodness of fit plots, bootstrap and visual predictive check were used for model internal validation. Data from another study were used for external validation.ResultsData from 16 male and 8 female subjects were used in the PopPK analysis. HS‐25 and M1 concentrations in the modelling cohort were well described by a 1‐compartment model incorporating first‐pass metabolism and a gallbladder compartment, accounting for the EHC process. The release kinetic of gall was mimicked by a first‐order constant plus a switch on/off effect. Body weight was identified as a significant covariate effecting on the clearance and apparent distribution volume of HS‐25, as well as , the transfer rate from metabolite compartment to gallbladder compartment. Internal and external validation demonstrated an acceptable predictive ability of the final model.ConclusionWe present the first PopPK model describing HS‐25 and M1 concentrations simultaneously, with the EHC process considered. The modelling and simulation results could provide reference for the clinical use of HS‐25.

01 Aug 2015·BioanalysisQ4 · MEDICINE

Simultaneous Determination of Hyzetimibe and its Main Active Metabolite in Plasma by LC–MS/MS and its Application in PK Study

Q4 · MEDICINE

Article

Author: Shao, Rong ; Jiang, Bo ; Lou, Honggang ; Ruan, Zourong ; Chen, Jinliang ; Wang, Jian’an

Background: Hyzetimibe is a new compound belonging to a novel class of selective cholesterol absorption inhibitors. A simple, highly sensitive LC–MS/MS method has been developed for the quantification of hyzetimibe and its main active metabolite, hyzetimibe-glucuronide, in human plasma. Results: Analytical samples were prepared using a protein precipitation method coupled with a concentration process. The linearity of this method was established for concentrations in the ranges of 0.05–50 and 0.5–500 ng/ml for hyzetimibe and hyzetimibe-glucuronide, respectively. The accuracy and precision of the method varied from 97.9 to 105% and 2.6 to 7.4%, respectively. Conclusion: This study represents the first reported example of an LC–MS/MS assay for the simultaneous quantification of hyzetimibe and its main active metabolite, hyzetimibe-glucuronide, in human plasma. Furthermore, this method has been successfully applied to a PK study.

100 Deals associated with Hyzetimibe

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	C10AX	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Primary hypercholesterolemia	CN	Zhejiang Hisun Pharmaceutical Co., Ltd.	25 Jun 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Atherosclerosis	Phase 1	CN	Zhejiang Hisun Pharmaceutical Co., Ltd.	07 Jun 2016
Coronary Disease	Phase 1	-	Zhejiang Hisun Pharmaceutical Co., Ltd.	07 Jun 2016
Primary hypercholesterolemia	Phase 1	-	Zhejiang Hisun Pharmaceutical Co., Ltd.	28 Feb 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03433196 (NEWS) Manual	Phase 3	Primary hypercholesterolemia	255	Atorvastatin strontium+海泽麦布	(hduwbbtshd) = qwivovyfdp jidccfhibp (qxhbwasmzp ) View more	Superior	12 Sep 2018
				Atorvastatin strontium+Atorvastatin strontium	(hduwbbtshd) = awrdepmgba jidccfhibp (qxhbwasmzp ) View more
NCT03413462 (NEWS) Manual	Phase 3	Primary hypercholesterolemia	374	海泽麦布	(voztvcaplk) = ssxqdeizyi wnhgqbccul (rgyvsoetqa )	Positive	12 Sep 2018
				Placebo	-