Delving into the Latest Updates on Cofrogliptin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

DPP-4

Mechanism

DPP-4 inhibitors(Dipeptidyl peptidase IV inhibitors)

Therapeutic Areas

Endocrinology and Metabolic DiseaseUrogenital Diseases

Active Indication

Diabetes Mellitus, Type 2Renal Insufficiency

Inactive Indication

Glucose Intolerance

Originator Organization

Sichuan Haisco Pharmaceutical Co., Ltd.

Active Organization

Haisco Pharmaceutical Group Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (18 Jun 2024),

Diabetes Mellitus, Type 2

RegulationSpecial Review Project (CN)

Login to view timeline

Structure

Molecular FormulaC18H19F5N4O3S

InChIKeyGUBOXFWNNXSQNH-SVGFKBNWSA-N

CAS Registry1844874-26-5

AbstractAimWe evaluated the efficacy and safety of cofrogliptin, a novel dipeptidyl peptidase‐4 inhibitor taken once every 2 weeks (Q2W), compared with linagliptin (taken daily) in patients with type 2 diabetes inadequately controlled on metformin in China.Materials and MethodsIn this phase 3 randomized, double‐blind, active‐controlled, multicentre study, patients were randomly assigned 1:1:1 to receive cofrogliptin 10 mg Q2W, cofrogliptin 25 mg Q2W, or linagliptin 5 mg daily, all as an add‐on treatment to metformin, for 24 weeks. Eligible patients could enter an open‐label extension period and receive cofrogliptin 25 mg Q2W for an additional 28 weeks. The primary endpoint was change in glycated haemoglobin from baseline to 24 weeks, with a non‐inferiority margin of 0.4% for cofrogliptin versus linagliptin treatment.ResultsOverall, 465 patients entered the 24‐week treatment period (median age: 57.0 years). The least‐squares mean (standard error) change in glycated haemoglobin from baseline to week 24 was −0.96 (0.063), −0.99 (0.064) and −1.07 (0.065) for the cofrogliptin 10 mg, cofrogliptin 25 mg and linagliptin 5 mg groups, respectively. The between‐group difference met the predefined margin for non‐inferiority of cofrogliptin (10 and 25 mg) versus linagliptin treatment. The incidence of common adverse events (≥5% patients) during the 24‐week treatment period was similar between treatment groups. There were no serious hypoglycaemic events.ConclusionIn Chinese patients with type 2 diabetes inadequately controlled on metformin, the glucose‐lowering effect of cofrogliptin (Q2W) was non‐inferior to linagliptin (daily), with a similar safety profile maintained over 52 weeks of treatment.

01 Jul 2024·Clinical Pharmacology in Drug Development

Concentration‐QTc Modeling of the DPP‐4 Inhibitor HSK7653 in a First‐in‐Human Study of Chinese Healthy Volunteers

Article

Author: Wu, Qinghe ; Chen, Kai ; Yan, Pangke ; Wang, Xiaoxu ; Niu, Xiaoye ; Niu, Shu ; Li, Fangqiong ; Li, Haiyan ; Wu, Nan ; Liu, Hongzhong ; Hu, Bei ; Cui, Cheng ; Liu, Dongyang

AbstractCofrogliptin (HSK7653) is a long‐acting dipeptidyl peptidase‐4 inhibitor for the treatment of type 2 diabetes mellitus with a twice‐monthly dosing regimen. This study included 62 participants (48 without food effect, 14 with food effect) receiving single doses of HSK7653 (5, 10, 25, 50, 100, and 150 mg) or placebo. Pharmacokinetic samples were collected over 24 hours postdosing and sampling times are aligned with 12‐lead electrocardiograms (ECGs) which were derived from continuous ECG recordings. For the concentration‐QT interval corrected for heart rate (C‐QTc) analysis, we used linear mixed‐effects modeling to characterize the correlation between plasma concentrations of HSK7653 and the change from baseline in the QT interval which was corrected by Fridericia's formula (ΔQTcF). The result showed that a placebo‐corrected Fridericia corrected QT interval (ΔΔQTcF) prolongation higher than 10 milliseconds is unlikely at the mean maximum observed concentration (Cmax) (411 ng/mL) associated with the recommended therapeutic doses (25 mg twice‐monthly), even at the highest supratherapeutic concentration (2425 ng/mL). Thus, HSK7653 does not significantly affect QT prolongation at either recommended doses or the highest supratherapeutic concentration.

01 Jul 2024·Diabetes, Obesity and Metabolism

Biotransformation and disposition characteristics of HSK7653, a novel long‐acting dipeptidyl peptidase‐4 inhibitor for the treatment of type 2 diabetes

Article

Author: Zhang, Hua ; Ma, Sheng ; Meng, Jian ; Bian, Yi‐cong ; Wu, Qing‐he ; Zhang, Feng‐yi ; Chen, Xiao‐yan ; Huang, Chen‐rong ; Miao, Li‐yan ; Hu, Tao

AbstractAimTo investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants.MethodsA single oral dose of 80 μCi (25 mg) [14C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood‐to‐plasma ratio, mass balance and metabolism of HSK7653.ResultsThe drug was well absorbed and reached a maximum concentration at 1.25 h. The drug‐related components (HSK7653 and its metabolites) were eliminated slowly, with a half‐life (t1/2) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood‐to‐plasma ratio (0.573‐0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6‐2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation.ConclusionHSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t1/2 of HSK7653 may contribute to its long‐lasting efficacy as a long‐acting dipeptidyl peptidase‐4 inhibitor.

100 Deals associated with Cofrogliptin

Login to view more data

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	CN	Haisco Pharmaceutical Group Co., Ltd.	18 Jun 2024

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Glucose Intolerance	Phase 2	CN	Haisco Pharmaceutical Group Co., Ltd.	19 Mar 2021
Renal Insufficiency	Phase 1	CN	Haisco Pharmaceutical Group Co., Ltd.	04 Aug 2022

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04564872 (HSK7653, EASD2023)	Phase 3	Diabetes Mellitus, Type 2 Add-on	-	HSK7653 10mg	(gxqiwiyvct) = zbwqahdtrd wsxdaaztln (eeytqwmidn, -1.08 to -0.83)	Positive	03 Oct 2023
				HSK7653 25mg	(gxqiwiyvct) = xjxhdamulu wsxdaaztln (eeytqwmidn, -1.12 to -0.87)
HSK7653 (ADA2023)	Not Applicable	Diabetes Mellitus, Type 2	475	HSK7653 10mg	(mcrjqlgkaz) = eryldtejnj judhpscwvi (ahsrujtjuz )	Positive	20 Jun 2023
				HSK7653 25mg	(mcrjqlgkaz) = lxnaymzwkw judhpscwvi (ahsrujtjuz )
NCT04556851 (NEWS) Manual	Phase 3	Diabetes Mellitus, Type 2	462	HSK 7653	(friefihoww) = HSK7653 片的两个剂量组均达到了临床终点，均能有效降低 2 型糖尿病患者的糖化血红蛋白，且显著优于安慰剂组，安全性与安慰剂类似 aorwooidoe (yciituujxd )	Positive	25 Aug 2022
				Placebo
NCT04564872 (NEWS) Manual	Phase 3	Diabetes Mellitus, Type 2	450	Metformin+HSK 7653	(lkvsihxjun) = 两个剂量组均能有效降低患者糖化血红蛋白，且每两周服用一次 HSK7653 片与每天服用一次阳性对照药利格列汀片的降幅相当 kurighhwza (eeajcgmvgh )	Non-inferior	25 Aug 2022
				Metformin+Linagliptin