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 DiseaseUrogenital Diseases+ [2]

Active Indication

Neuralgia, PostherpeticDiabetic peripheral neuropathic painNeuralgia+ [4]

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

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]

NCT06490484 / RecruitingPhase 2

Efficacy and Safety of HSK16149 Capsule in Chinese Patients With Diabetic Peripheral Neuropathic Pain Who Had an Inadequate Response to Pregabalin: A Prospective, Multicenter, Randomized, Double-Blind, Double-Dummy, Pregabalin-controlled Phase 2 Study

Investigate the efficacy and safety of HSK16149 capsule in Chinese patients with Diabetic Peripheral Neuropathic Pain (DPNP) who had an inadequate response to Pregabalin, following 4 weeks treatment in comparison to Pregabalin

Start Date19 Apr 2024

Sponsor / Collaborator

Haisco Pharmaceutical Group Co., Ltd.

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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6

Literatures (Medical) associated with Crisugabalin

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.

01 Mar 2021·Journal of Pharmacology and Experimental TherapeuticsQ3 · MEDICINE

Pharmacology and Mechanism of Action of HSK16149, a Selective Ligand of α2δ Subunit of Voltage-Gated Calcium Channel with Analgesic Activity in Animal Models of Chronic Pain

Q3 · MEDICINE

Article

Author: Ye, Fei ; Yu, Xiaojuan ; Li, Yao ; Tan, Bowei ; Chen, Lei ; Gou, Xiaoli ; Shi, Zongjun ; Bai, Dongdong ; Zheng, Xiaoxiao ; Liang, Yong ; Qian, Meilin ; Cao, Pingfeng ; Ni, Jia

Chronic pain is a public health problem because current treatments are unsatisfactory with small therapeutic index. Although pregabalin is effective for treating chronic pain, the clinical use is limited because of its side effects. Therefore, improving its therapeutic index is essential. In this study, HSK16149 was found to be a novel ligand of voltage-gated calcium channel (VGCC) α ₂ δ subunit. HSK16149 inhibited [³H]gabapentin binding to the α ₂ δ subunit and was 23 times more potent than pregabalin. In two rat models of neuropathic pain, the minimum effective dose (MED) of HSK16149 was 10 mg/kg, and the efficacy was similar to that of 30 mg/kg pregabalin. Moreover, the efficacy of HSK16149 could persist up to 24 hours postadministration at 30 mg/kg, whereas the efficacy of pregabalin lasted only for 12 hours at 30 mg/kg in streptozotocin-induced diabetic neuropathy model, indicating that HSK16149 might be a longer-acting drug candidate. HSK16149 could also inhibit mechanical allodynia in intermittent cold stress model and decrease phase II pain behaviors in formalin-induced nociception model. In addition, the locomotor activity test showed that the MED of HSK16149 was similar to that of pregabalin, whereas in the Rotarod test, the MEDs of HSK16149 and pregabalin were 100 and 30 mg/kg, respectively. These findings indicated that HSK16149 might have a better safety profile on the central nervous system. In summary, HSK16149 is a potent ligand of VGCC α ₂ δ subunit with a better therapeutic index than pregabalin. Hence, it could be an effective and safe drug candidate for treating chronic pain. SIGNIFICANCE STATEMENT: As a novel potent ligand of voltage-gated calcium channel α ₂ δ subunit, HSK16149 has the potential to be an effective and safe drug candidate for the treatment of chronic pain.

International Journal of Molecular Sciences

Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials

Review

Author: García-Parra, Beliu ; Huerta, Miguel Á ; Serrano-Afonso, Ancor ; Paniagua, Nancy ; Garcia, Miguel M

The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.

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
Pain, Postoperative	Phase 2	CN	Haisco Pharmaceutical Group Co., Ltd.	08 Mar 2023
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

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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	(hhphuzfrdr) = dbiyjgjiiu lqfgehcwah (ppocqztxly )	Positive	21 Jun 2024
				lipoic acid (LA) combined with acetyl-levo-carnitine	(hhphuzfrdr) = wtsjcikopv lqfgehcwah (ppocqztxly )
ADA2023	Not Applicable	Diabetic peripheral neuropathic pain	-	Placebo	dvnqodigin(fgsffqmvvv) = ybczwgtxgu tfuwjwwttt (wlulwomhfu )	Positive	20 Jun 2023
				HSK 16149 40mg/d	dvnqodigin(fgsffqmvvv) = fgpgdzzqpq tfuwjwwttt (wlulwomhfu )