Delving into the Latest Updates on Evocalcet with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Evocalcet (JAN/INN), 伊万卡塞

+ [5]

Target

CaSR

Mechanism

CaSR agonists(Calcium sensing receptor agonists)

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseOther Diseases+ [1]

Active Indication

HypercalcemiaHyperparathyroidism, PrimaryParathyroid Neoplasms+ [2]

Inactive Indication-

Originator Organization

Mitsubishi Tanabe Pharma Corp.

Active Organization

Kyowa Kirin Co., Ltd.Kyowa Kirin Korea Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (23 Mar 2018),

Hyperparathyroidism, Secondary

Regulation-

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Structure/Sequence

Molecular FormulaC24H26N2O2

InChIKeyRZNUIYPHQFXBAN-XLIONFOSSA-N

CAS Registry870964-67-3

主要试验目的：在健康受试者体内，分别在空腹和餐后状态下，以協和キリン株式会社持有的依伏卡塞片（规格：2 mg；商品名：Orkedia®）为参比制剂，研究仁合益康汇泽药业河北有限公司研制的依伏卡塞片（规格：2 mg；受试制剂）的药代动力学，评价受试制剂与参比制剂是否具有生物等效性。次要试验目的：观察受试制剂和参比制剂在健康受试者中的安全性。

[Translation]

Main purpose of the test: In healthy subjects, under fasting and postprandial conditions, evocarnet tablets (specification: 2 mg; trade name: Orkedia®) held by Kyowa Coron Co., Ltd. were used as the reference preparation. Study the pharmacokinetics of evocarnet tablets (specification: 2 mg; test preparation) developed by Renhe Yikang Huize Pharmaceutical Hebei Co., Ltd., and evaluate whether the test preparation and the reference preparation are bioequivalent. Secondary test purpose: to observe the safety of the test preparation and reference preparation in healthy subjects.

Start Date03 May 2024

Sponsor / Collaborator

Renhe Yikang Huize Pharmaceutical Hebei Co., Ltd.

CTR20241321

/ CompletedNot Applicable

依伏卡塞片人体生物等效性试验

[Translation] Bioequivalence study of Ivocasert tablets in human subjects

以中国健康受试者为试验对象，采用自身交叉对照的试验设计，测定杭州仟源保灵药业有限公司研制的依伏卡塞片（规格：2 mg）给药后依伏卡塞在健康受试者体内的血药浓度经时过程，估算相应的药代动力学参数，并以协和麒麟株式会社持证和生产的依伏卡塞片(规格：2 mg，商品名：Orkedia®)为参比制剂，考察受试制剂的相对生物利用度，评价制剂间的生物等效性，并观察受试制剂和参比制剂在中国健康受试者中的安全性。

[Translation]

Healthy Chinese subjects were used as test subjects. A self-crossover design was used to determine the time course of plasma concentration of ivocate in healthy subjects after administration of ivocate tablets (specification: 2 mg) developed by Hangzhou Qianyuan Baoling Pharmaceutical Co., Ltd., and to estimate the corresponding pharmacokinetic parameters. Ivocasert tablets (specification: 2 mg, trade name: Orkedia®) certified and produced by Kyowa Kirin Co., Ltd. were used as reference preparations to investigate the relative bioavailability of the test preparations, evaluate the bioequivalence between the preparations, and observe the safety of the test preparations and reference preparations in healthy Chinese subjects.

Start Date21 Apr 2024

Sponsor / Collaborator

Hangzhou QIANYUAN Pollen Pharmaceutical Co., Ltd.

CTR20240573

/ CompletedNot Applicable

中国健康受试者空腹及餐后状态下单次口服依伏卡塞片（规格：2mg）的一项单中心、随机、开放、两制剂、两序列、两周期交叉生物等效性试验

[Translation] A single-center, randomized, open-label, two-formulation, two-sequence, two-period crossover bioequivalence study of a single oral dose of ivocate tablets (strength: 2 mg) in healthy Chinese subjects under fasting and fed conditions

主要研究目的：考察中国健康受试者空腹及餐后条件下单次口服依伏卡塞片受试制剂（规格：2mg，生产厂家：江西科睿药业有限公司）及参比制剂（商品名：Orkedia®，规格：2mg，持证商：協和キリン株式会社）后的药代动力学特征，评价两制剂在空腹和餐后条件下是否具有生物等效性。次要研究目的：评价依伏卡塞片受试制剂（规格：2mg）及参比制剂（商品名：Orkedia®，规格：2mg）在健康受试者中的安全性。

[Translation]

Main research purpose: To examine the test preparation (specification: 2 mg, manufacturer: Jiangxi Kerui Pharmaceutical Co., Ltd.) and the reference preparation (trade name) of evocarset tablets taken orally in Chinese healthy subjects under fasting and postprandial conditions. : Orkedia®, strength: 2 mg, license holder: Kyowa Kirin Co., Ltd.) to evaluate whether the two preparations are bioequivalent under fasting and postprandial conditions. Secondary research purpose: To evaluate the safety of the test preparation (strength: 2 mg) of evocarset tablets and the reference preparation (trade name: Orkedia®, strength: 2 mg) in healthy subjects.

Start Date26 Mar 2024

Sponsor / Collaborator

Jiangxi Kerui Pharmaceutical Co., Ltd

100 Clinical Results associated with Evocalcet

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100 Translational Medicine associated with Evocalcet

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100 Patents (Medical) associated with Evocalcet

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49

Literatures (Medical) associated with Evocalcet

01 Jan 2025·BMJ Case Reports

Severe hypophosphataemia following denosumab administration successfully managed using a calcimimetic agent

Article

Author: Matsukawa, Yukihiro ; Ikeda, Yuhachi ; Omori, Makiko ; Sakai, Tomoyuki

Denosumab, an anti-RANKL antibody, induces bone metabolism to a low-turnover bone status by arresting osteoclast activity. Frequent adverse events include infusion reactions, fever and hypocalcaemia but not hypophosphataemia. We report a case of severe hypophosphataemia associated with secondary hyperparathyroidism following denosumab administration in a young boy with recurrent osteosarcoma who was successfully treated with evocalcet. He developed hypocalcaemia and severe refractory hypophosphataemia after receiving denosumab for bone metastases despite calcium, cholecalciferol and phosphorus supplementation. Laboratory data revealed secondary hyperparathyroidism due to denosumab-induced hypocalcaemia as the cause of hypophosphataemia. Evocalcet contributed to the normalised parathyroid hormone and phosphorus levels, allowing the discontinuation of phosphorus supplementation. This case highlights the complexity of managing electrolyte imbalances induced by bone-modifying agents, such as denosumab, underscoring the importance of monitoring bone metabolism markers and the potential effectiveness of evocalcet in managing drug-induced secondary hyperparathyroidism and hypophosphataemia.

01 Nov 2024·BMJ Case Reports

Paradoxical cerebral embolism caused by patent foramen ovale in a patient with multiple endocrine neoplasia type 1 and severe primary hyperparathyroidism

Article

Author: Sekiya, Motohiro ; Matsuda, Takaaki ; Shimano, Hitoshi ; Osaki, Yoshinori

A man in his late 30s with gait difficulty, dysarthria, impaired consciousness and polyuria was diagnosed with left thalamic infarction. Hypercalcaemia (3.52 mmol/L (2.15–2.52)), high intact-parathyroid hormone (i-PTH) levels (88.8 pmol/L (1.1–6.9)) and high D-dimer levels (14.7 mg/L (<1.0)) were identified, followed by a positive microbubble test on transesophageal echocardiogram, suggesting high-risk patent foramen ovale (PFO) for ischaemic stroke. Paradoxical cerebral embolism via PFO, complicated by a hypercoagulable state and hypercalcemic dehydration, was considered. Polyglandular parathyroid hyperplasia, plus radiolucent mandibular tumours, suggested multiple endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumour syndrome. Genetic testing confirmed MEN1. Treatment was 24 mg of oral evocalcet and total parathyroidectomy with forearm autotransplantation, resulting in improved serum calcium and i-PTH levels. Finally, he underwent transcatheter PFO closure. We emphasise careful, etiological pursuit in young-onset stroke and the usefulness of genetic testing in differentiating hyperparathyroidism associated with mandibular tumours.

01 Oct 2024·European Journal of Clinical Pharmacology

Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis

Article

Author: Yang, Rui ; Jin, Lie ; Zhou, Limei ; Liu, Xing ; Li, Zhouzhou ; Zheng, Peimin ; Chen, Peipei ; Mei, Ziwei ; Liu, Yichen ; Xie, Xun

OBJECTIVEActive vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism.METHODSWe included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes.RESULTSTwenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions.CONCLUSIONThe same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

100 Deals associated with Evocalcet

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External Link

KEGG	Wiki	ATC	Drug Bank
D11063	Evocalcet	H03	DB12388

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hypercalcemia	JP	Kyowa Kirin Co., Ltd.	20 Dec 2019
Hyperparathyroidism, Primary	JP	Kyowa Kirin Co., Ltd.	20 Dec 2019
Parathyroid Neoplasms	JP	Kyowa Kirin Co., Ltd.	20 Dec 2019
Hyperparathyroidism, Secondary	JP	Kyowa Kirin Co., Ltd.	23 Mar 2018

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperparathyroidism, Secondary	Phase 3	TW	Kyowa Kirin Co., Ltd.	09 Apr 2019
Hyperparathyroidism, Secondary	Phase 3	HK	Kyowa Kirin Co., Ltd.	09 Apr 2019
Chronic Kidney Diseases	Phase 3	CN	Kyowa Kirin Co., Ltd.	13 Feb 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2022	Not Applicable	Uremia	-	Evocalcet	svgefgohdd(sywfddnxah) = ljgauiznto opluoyrggj (jhfwunljiv ) View more	Positive	03 Nov 2022
ASN2022	Not Applicable	Uremia	-	Cinacalcet	svgefgohdd(sywfddnxah) = gxcweapjvv opluoyrggj (jhfwunljiv ) View more	Positive	03 Nov 2022
NCT03822507 (ORCHESTRA Trial, ASN2022)	Phase 3	Hyperparathyroidism, Secondary iPTH level	-	Evocalcet	bloogotlej(hazhlxvyyt) = pkbppbudvm odtlxsclek (ygyjqsbztt ) View more	Positive	03 Nov 2022
NCT03822507 (ORCHESTRA Trial, ASN2022)	Phase 3	Hyperparathyroidism, Secondary iPTH level	-	Cinacalcet	bloogotlej(hazhlxvyyt) = rvqxhpqtdt odtlxsclek (ygyjqsbztt ) View more	Positive	03 Nov 2022
NCT03280264 (CTgov)	Phase 3	Hypercalcemia \| Hyperparathyroidism, Primary \| Parathyroid Neoplasms	18	KHK7580	qaoxosyrac(fykkteweuv) = reiswckrvp yasgmwfpkr (vrprqfclvz, mviajxdmtg - olcuvgmaqs) View more	-	27 May 2021
NCT03280264 (Pubmed \| J Bone Miner Metab) Manual	Phase 3	Hyperparathyroidism, Primary	18	Evocalcet	(hvttuvkefk) = arzdkjqltq husfpoyuat (bqdymcuwpk, 52.4 - 93.6) View more	Positive	01 Sep 2020
P0886 (ERA2020)	Not Applicable	-	34	Evocalcet	(wrdcwnwdig) = occurred in 2 patients jbvhkcjjbi (meqfabpjzk ) View more	Positive	06 Jun 2020
NCT02549417 \| JPRN-JapicCTI-153016 (Pubmed \| Clin Exp Nephrol)	Phase 3	-	39	Evocalcet 1-8 mg	(hiublmzonb) = Adverse drug reactions occurred in 46.2% (18/39) of patients, with most being of mild-to-moderate severity including GI-related events txfdfqikze (bjospsadaw )	Positive	01 Jun 2019
NCT02549391 (Pubmed) Manual	Phase 3	Hyperparathyroidism, Secondary	634	Evocalcet	(bsveqkirjj) = fztgvtjhup frgshqizwh (uexnsitttd ) View more	Non-superior	01 Oct 2018
NCT02549391 (Pubmed) Manual	Phase 3	Hyperparathyroidism, Secondary	634	Cinacalcet	(bsveqkirjj) = efamlyxwrh frgshqizwh (uexnsitttd ) View more	Non-superior	01 Oct 2018