Delving into the Latest Updates on Crisugabalin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

克利加巴林

+ [2]

Target

CACNA2D1

Mechanism

CACNA2D1 blockers(Voltage-gated calcium channel alpha2/delta subunit 1 blockers)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic DiseaseOther Diseases+ [3]

Active Indication

Neuralgia, PostherpeticDiabetic peripheral neuropathic painNeuralgia+ [5]

Inactive Indication-

Originator Organization

Haisco Pharmaceutical Group Co., Ltd.

Active Organization

Haisco Pharmaceutical Group Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (15 May 2024),

Diabetic peripheral neuropathic pain

Regulation-

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Structure/Sequence

Molecular FormulaC12H19NO2

InChIKeyWCEFMBSFXJUREW-LIJGXYGRSA-N

CAS Registry2209104-84-5

主要目的与安慰剂比较，评估 HSK16149 胶囊（以下简称为 HSK16149）治疗中重度中枢神经病理性疼痛的有效性。次要目的评估 HSK16149 相比安慰剂治疗中重度中枢神经病理性疼痛的安全性。评估 HSK16149 治疗中重度中枢神经病理性疼痛（52 周）的长期安全性和有效性。评估 HSK16149 在中国中重度中枢神经病理性疼痛患者中的药代动力学（PK）特征。

[Translation]

Primary Objective To evaluate the efficacy of HSK16149 capsules (hereinafter referred to as HSK16149) in the treatment of moderate to severe central neuropathic pain compared with placebo. Secondary Objectives To evaluate the safety of HSK16149 compared with placebo in the treatment of moderate to severe central neuropathic pain. To evaluate the long-term safety and efficacy of HSK16149 in the treatment of moderate to severe central neuropathic pain (52 weeks). To evaluate the pharmacokinetic (PK) characteristics of HSK16149 in Chinese patients with moderate to severe central neuropathic pain.

Start Date23 May 2024

Sponsor / Collaborator

Haisco Pharmaceutical Group Co., Ltd.

[+1]

100 Clinical Results associated with Crisugabalin

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100 Translational Medicine associated with Crisugabalin

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100 Patents (Medical) associated with Crisugabalin

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7

Literatures (Medical) associated with Crisugabalin

01 Jan 2025·Journal of Chromatography B

Quantification of crisugabalin (HSK16149) in biological matrix by LC-MS/MS method: An application to rat pharmacokinetic and tissue distribution studies

Article

Author: Dou, Caixia ; Li, Yao ; Wang, Ju ; Chen, Xiaoyan ; Tang, Pingming ; Peng, Ni ; Shen, Jiale ; Wang, Zeyu

Crisugabalin (HSK16149), a novel VGCC α2δ ligand, has been approved for the treatment of adult diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN). In this study, an LC-MS/MS method was developed for the determination of crisugabalin in rat plasma and tissues homogenate. Samples were extracted by protein precipitation and separated on a Hypersil GOLD aQ column with methanol and 2 mM ammonium acetate in water containing 0.1 % formic acid as mobile phase. Crisugabalin and its internal standard HSK7891 were ionized by electrospray ionization source and detected by multiple reaction monitoring with transitions of m/z 210.9 → 134.4 and m/z 246.0 → 129.3. Over the range of 0.0100-10.0 μg/mL, the selectivity, linearity, precision and accuracy, matrix effect, stability, recovery and dilution integrity of crisugabalin were validated in rat plasma. Validation was also performed in rat liver homogenate at concentrations ranging from 0.0200-20.0 μg/g. The method was then successfully applied to determine the pharmacokinetics and tissue distribution of crisugabalin. In rats, orally administered crisugabalin was completely and rapidly absorbed with a peak time of about 0.57 h, and was mainly distributed to kidney, bladder and liver tissues. Crisugabalin exhibited linear pharmacokinetics over the oral dose range of 3-30 mg/kg.

01 Nov 2024·JAMA Dermatology

Efficacy and Safety of Crisugabalin (HSK16149) in Adults with Postherpetic Neuralgia

Article

Author: Qin, Lanying ; Chen, Xiaoyan ; Wang, Yaping ; Wu, Liming ; Bai, Nianyue ; Yang, Chunjun ; Li, Xiangkui ; Cheng, Zhigang ; Zhang, Tangde ; Yang, Zhenling ; Yu, Chunshui ; Yang, Xiumin ; Jin, Zhehu ; Wu, Wenzhong ; Chen, Rixin ; Yang, Dong ; Sun, Hui ; Shi, Jihai ; Li, Fangqiong ; Lei, Tiechi ; Wang, Dongmei ; Yu, Nan ; Wu, Tingting ; Li, Chenyu ; Zhang, Daying ; Zhu, Shoumin ; Wang, Yu ; Ba, Xiaohong ; Feng, Zhiying ; Lu, Qianjin ; Lin, Xuewu ; Zhang, Tong ; Ye, Zhijian ; Zhang, Jianglin ; Zhang, Shoumin ; Zhang, Weiyi ; Shi, Kemei ; Lu, Jianyun ; Zhang, Zhuobo ; Zhang, Guoqiang ; Yin, Wenhao ; Han, Xiuping ; Lu, Shousi ; Qin, Pingping ; Li, Xin ; Wan, Li ; Gao, Ying ; Li, Linfeng ; Wang, Huiping ; Liu, Changyi ; Wang, Guonian

ImportanceChina carries a heavy burden of postherpetic neuralgia, with an unmet need for novel drugs with greater efficacy and less prominent neurotoxic effects than existing calcium channel ligands.ObjectiveTo investigate the efficacy and safety of crisugabalin, an oral calcium channel α2δ-1 subunit ligand, for postherpetic neuralgia.Design, Setting, and ParticipantsThis randomized clinical trial, carried out between November 9, 2021, and January 5, 2023, at 48 tertiary care centers across China had 2 parts. Part 1 was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisting of a 2-week screening period, a 7-day run-in period, and a 12-week double-blind treatment period. Part 2 was a 14-week open-label extension study. Investigators, statisticians, trial clinicians, and patients were blinded to trial group assignments. Participants included adults with postherpetic neuralgia with an average daily pain score (ADPS) of at least 4 on the 11-point Numeric Pain Rating Scale over the preceding week, with the exclusion of patients with pain not controlled by prior therapy with pregabalin (≥300 mg/d) or gabapentin (≥1200 mg/d).InterventionsPatients were randomized 1:1:1 to receive crisugabalin, 20 mg twice daily (ie, 40 mg/d), and crisugabalin, 40 mg twice daily (ie, 80 mg/d), or placebo for 12 weeks. Eligible patients received crisugabalin, 40 mg, twice daily during extension.Main Outcome and MeasureThe primary efficacy end point was the change from baseline in ADPS at week 12.ResultsThe study enrolled 366 patients (121 patients receiving crisugabalin, 40 mg/d; 121 patients receiving crisugabalin, 80 mg/d; 124 patients receiving placebo; median [IQR] age, 63.0 [56.0-69.0] years; 193 men [52.7%]). At week 12, the least squares mean (SD) change from baseline in ADPS was −2.2 (0.2) for crisugabalin, 40 mg/d, and −2.6 (0.2) for crisugabalin, 80 mg/d, vs −1.1 (0.2) for placebo, with a least squares mean difference of −1.1 (95% CI, −1.6 to −0.7; P &lt; .001) and −1.5 (−95% CI, −2.0 to −1.0; P &lt; .001) vs placebo, respectively. No new safety concerns emerged.Conclusions and RelevanceCrisugabalin, 40 mg/d, or crisugabalin, 80 mg/d, was well tolerated and demonstrated a statistically significant improvement in ADPS over placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT05140863

01 Jun 2023·Pharmacology research & perspectives

Effect of a high-fat and high-calorie food on the pharmacokinetics of a novel, potent GABA analog HSK16149 in healthy subjects.

Article

Author: Wang, Wei ; Zhang, Mengqi ; Zeng, Weifang ; Jia, Jingying ; Wu, Qingqing ; Li, Fangqiong ; Zhu, Huijuan ; Yu, Chen ; Liu, Yanmei ; Song, Rong

HSK16149 is a novel, potent gamma-aminobutyric acid (GABA) analog for the treatment of neuropathic pain. The purpose of this study was to assess the effect of a high-fat and high-calorie meal on the pharmacokinetics of HSK16149 in healthy Chinese subjects. An open-label, two-period crossover design was applied in this study. Twenty-six subjects were enrolled and were randomly divided into two groups: a fasted-fed group and a fed-fasted group, with 13 subjects in each group. Subjects took a single oral dose of 45 mg of HSK16149 under fasted or fed conditions on Day 1 and Day 4. A series of blood samples were collected for PK analysis. Safety was evaluated throughout the study by physical examinations, clinical laboratory tests, 12-lead ECGs, vital signs, and adverse events (AEs). The parameters AUC_0-∞ , AUC_0-t , and C_max of HSK16149 were compared to assess the bioequivalence of HSK16149 under fasted and fed conditions. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) of AUC_0-t and AUC_0-∞ under the fed condition compared with the fasted condition were 95.84% (91.94-99.90%) and 95.79% (91.89-99.84%), respectively, which were all within the bioequivalent interval (80.00-125.00%). The GMR (90% CI) of C_max under the fed condition compared with the fasted condition was 66.04% (59.45-73.36%), which was not within the bioequivalent range (80.00-125.00%). All adverse events were transient and resolved. This study demonstrated that HSK16149 can be administered with or without food.

100 Deals associated with Crisugabalin

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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Neuralgia, Postherpetic	CN	Haisco Pharmaceutical Group Co., Ltd.	28 Jun 2024
Diabetic peripheral neuropathic pain	CN	Haisco Pharmaceutical Group Co., Ltd.	15 May 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neuralgia	Phase 3	-	Haisco Pharmaceutical Group Co., Ltd.	30 May 2024
Peripheral neuralgia	Phase 3	CN	Haisco Pharmaceutical Group Co., Ltd.	17 Feb 2022
Pain, Postoperative	Phase 2	CN	Haisco Pharmaceutical Group Co., Ltd.	08 Mar 2023
Diabetic peripheral neuropathy	Phase 2	CN	Haisco Pharmaceutical Group Co., Ltd.	01 Apr 2021
Post-herpetic neuritis	Phase 1	CN	Haisco Pharmaceutical Group Co., Ltd.	20 Mar 2023
Renal Insufficiency	Phase 1	CN	Haisco Pharmaceutical Group Co., Ltd.	12 Dec 2022
Fibromyalgia	IND Approval	CN	Haisco Pharmaceutical Group Co., Ltd.	17 Apr 2024
Diabetic Neuropathies	Preclinical	CN	Haisco Pharmaceutical Group Co., Ltd.	28 Dec 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06122012 (ADA2024) Manual	Phase 2	Diabetic peripheral neuropathic pain	134	Crisugabalin with Acetyl-Levo-Carnitine	(asltwmkxce) = jlotcaogap zwwfwdppgc (dptmdyklwh )	Positive	21 Jun 2024
				lipoic acid (LA) combined with acetyl-levo-carnitine	(asltwmkxce) = ntmmppmzot zwwfwdppgc (dptmdyklwh )
ADA2023	Not Applicable	Diabetic peripheral neuropathic pain	-	Placebo	lqntpwgcxz(hszoslsksm) = itnyzkbvhx qlmllbbdjq (zpcorzoplr )	Positive	20 Jun 2023
				HSK 16149 40mg/d	lqntpwgcxz(hszoslsksm) = uskgcoyzsz qlmllbbdjq (zpcorzoplr )