[Translation] A single-center, open-label, randomized, single-dose, four-period, two-sequence, fully repeated crossover bioequivalence study was conducted to evaluate the bioequivalence of the test preparation, sodium valproate extended-release tablets (I) (strength: 0.5 g), and the reference preparation, Depakine (strength: 0.5 g), in healthy adult subjects in the fasting and fed state.

主要研究目的：研究空腹和餐后状态下单次口服受试制剂丙戊酸钠缓释片（I）（规格：0.5g，辰欣药业股份有限公司生产）与参比制剂丙戊酸钠缓释片（I）（德巴金，规格：0.5g，赛诺菲（杭州）制药有限公司生产）在健康受试者体内的药代动力学，评价空腹和餐后状态下口服两种制剂的生物等效性。次要研究目的：评估受试制剂丙戊酸钠缓释片（I）（规格：0.5g）和参比制剂丙戊酸钠缓释片（I）（德巴金，规格：0.5g）在健康受试者中的安全性。

[Translation]

The main purpose of the study is to study the pharmacokinetics of the test preparation sodium valproate sustained-release tablets (I) (specification: 0.5g, produced by Chenxin Pharmaceutical Co., Ltd.) and the reference preparation sodium valproate sustained-release tablets (I) (Depakin, specification: 0.5g, produced by Sanofi (Hangzhou) Pharmaceutical Co., Ltd.) in healthy subjects after a single oral administration under fasting and fed conditions, and to evaluate the bioequivalence of the two preparations when taken orally under fasting and fed conditions. Secondary purpose of the study is to evaluate the safety of the test preparation sodium valproate sustained-release tablets (I) (specification: 0.5g) and the reference preparation sodium valproate sustained-release tablets (I) (Depakin, specification: 0.5g) in healthy subjects.

Start Date04 Jun 2024

Sponsor / Collaborator

Cisen Pharmaceutical Ltd.

CTR20240582 / CompletedNot Applicable

丙戊酸钠缓释片（Ⅰ）（0.5g）在中国健康受试者中餐后给药条件下随机、开放、单剂量、两序列、四周期、完全重复交叉生物等效性试验

[Translation] A randomized, open-label, single-dose, two-sequence, four-period, fully repeated crossover bioequivalence study of sodium valproate sustained-release tablets (I) (0.5 g) in Chinese healthy subjects after meal administration

主要研究目的：按有关生物等效性试验的规定，选择Sanofi Aventis France为持证商且生产的丙戊酸钠缓释片（商品名：Depakine® Chrono，规格：500mg）为参比制剂，对四川科伦药业股份有限公司生产并提供的受试制剂丙戊酸钠缓释片（I）（规格：0.5g）进行餐后给药人体生物等效性试验，比较受试制剂中药物的吸收速度和吸收程度与参比制剂的差异是否在可接受的范围内，评价两种制剂在餐后给药条件下的生物等效性。次要研究目的：观察健康受试者口服受试制剂丙戊酸钠缓释片（I）（规格：0.5g）和参比制剂丙戊酸钠缓释片（商品名：Depakine® Chrono，规格：500mg）的安全性。

[Translation]

Main study purpose: According to the relevant provisions of bioequivalence test, the sodium valproate sustained-release tablets (trade name: Depakine® Chrono, specification: 500mg) produced by Sanofi Aventis France as the licensee was selected as the reference preparation, and the test preparation sodium valproate sustained-release tablets (I) (specification: 0.5g) produced and provided by Sichuan Kelun Pharmaceutical Co., Ltd. were used for postprandial human bioequivalence test, to compare whether the absorption rate and degree of the drug in the test preparation were within the acceptable range with the reference preparation, and to evaluate the bioequivalence of the two preparations under postprandial administration conditions. Secondary study purpose: To observe the safety of oral administration of the test preparation sodium valproate sustained-release tablets (I) (specification: 0.5g) and the reference preparation sodium valproate sustained-release tablets (trade name: Depakine® Chrono, specification: 500mg) in healthy subjects.

Start Date27 Mar 2024

Sponsor / Collaborator

Sichuan Kelun Pharmaceutical Co., Ltd.

CTR20234171 / CompletedNot Applicable

丙戊酸钠缓释片（I）在中国健康受试者中单中心、随机、开放、单剂量、两制剂、四周期、两序列、重复交叉空腹/餐后状态下生物等效性试验

[Translation] A single-center, randomized, open-label, single-dose, two-formulation, four-period, two-sequence, repeated crossover bioequivalence study of sodium valproate extended-release tablets (I) in Chinese healthy subjects under fasting/fed conditions

主要研究目的：健康受试者空腹或餐后状态下，单次口服山东中健康桥制药有限公司生产的受试制剂丙戊酸钠缓释片（I）[规格：0.5g（以丙戊酸钠计，每片含丙戊酸钠333mg、丙戊酸145mg））]或持证商为Sanofi Aventis France的参比制剂丙戊酸钠缓释片[商品名：Depakine Chrono®；规格：500mg（以丙戊酸钠计）]，分别考察空腹或餐后状态下受试制剂与参比制剂在健康受试者体内的药代动力学参数，评价两制剂的生物等效性。次要研究目的：考察受试制剂和参比制剂在健康受试者中的安全性。

[Translation]

Main study objectives: Healthy subjects were given a single oral dose of the test preparation sodium valproate sustained-release tablets (I) [Specification: 0.5g (calculated as sodium valproate, each tablet contains 333mg sodium valproate and 145mg valproic acid)] produced by Shandong Zhongjiankangqiao Pharmaceutical Co., Ltd. or the reference preparation sodium valproate sustained-release tablets [trade name: Depakine Chrono®; Specification: 500mg (calculated as sodium valproate)] produced by Sanofi Aventis France, in the fasting or postprandial state, to investigate the pharmacokinetic parameters of the test preparation and the reference preparation in healthy subjects, respectively, and to evaluate the bioequivalence of the two preparations. Secondary study objectives: Investigate the safety of the test preparation and the reference preparation in healthy subjects.

Start Date04 Jan 2024

Sponsor / Collaborator

Shandong Baicao Medicine Co. Ltd.

100 Clinical Results associated with Sodium Valproate

100 Translational Medicine associated with Sodium Valproate

100 Patents (Medical) associated with Sodium Valproate

4,009

Literatures (Medical) associated with Sodium Valproate

30 Dec 2024·Acta neurologica Taiwanica

Taste Disorder and Tongue Numbness After Lithium Overdose.

Article

Author: Chu, Si-Yu ; Wang, Huang-Chi ; Hsieh, Ming-Hong ; Chang, Cheng-Chen

PURPOSE:

Drug-induced taste disturbances are prevalent in clinical practice, with dysgeusia being a frequent manifestation. This study aims to present a case of taste disorders and tongue numbness induced by a lithium overdose.

CASE REPORT:

A 33-year-old woman with bipolar II disorder attempted suicide by ingesting multiple drugs, including lithium and benzodiazepines. She exhibited weakness but was conscious after admission. Laboratory analyses indicated elevated serum lithium and urine benzodiazepine levels. Admitted to a psychiatric ward, her symptoms included diarrhea, poor appetite, and postprandial nausea. Two weeks later, she reported altered taste sensations and tongue numbness following the overdose. Her ongoing medication included venlafaxine, valproate sodium, and clozapine. Symptoms improved over time without specific treatment, aligning with increased appetite and weight gain.

CONCLUSION:

Drug-induced taste disturbances have a substantial impact on patients' quality of life and medication adherence. This case brings attention to taste disorders induced by lithium and suggests potential mechanisms that could contribute to taste alterations. It underscores the importance of conducting thorough assessments in patients experiencing gustatory symptoms, particularly during the ongoing pandemic.

01 Feb 2024·Epilepsy research

The impact of antiseizure medication on bone health: A systematic review of animal studies

Review

Author: Parveen, Abida ; Parveen, Bushra ; Parveen, Rabea ; Vohora, Divya ; Penumallu, Naveen Reddy ; Shaik, Abdul Rahaman

BACKGROUND:

Antiseizure medications (ASMs) are known to potentially impact bone health, but existing literature presents conflicting results regarding their specific effects on bone mineralization, metabolism, and quality.

OBJECTIVE:

This systematic review aims to establish a consensus regarding the influence of ASMs on bone health based on existing preclinical studies.

METHODS:

Following SYRCLE and PRISMA guidelines, we conducted a systematic search in PubMed, Science Direct, and Google Scholar to identify relevant studies. Ultimately, 21 articles were selected for inclusion in this review.

RESULTS:

Among the chosen studies, approximately half involved Wistar rats as experimental subjects. Levetiracetam and sodium valproate were the most frequently investigated drugs, with a typical treatment duration of 10-12 weeks. These studies exhibited a low risk of bias in aspects like sequence generation, random housing, random outcome assessment, and reporting bias. However, blinding in performance, allocation concealment, and detection were often rated as having a high risk of bias. The collective findings suggest that prolonged ASM use leads to reduced bone mineral density, altered bone turnover marker levels (including hypovitaminosis D, hypocalcemia, and secondary hyperparathyroidism), deterioration of bone microarchitecture, and decreased mechanical strength.

CONCLUSION:

The adverse effects on bone associated with ASMs are not limited to enzyme-inducing drugs, as newer generation ASMs may also contribute to these effects. Hypovitaminosis D alone may not be solely responsible for ASM-induced bone issues, suggesting the involvement of other mechanisms. Furthermore, substantial variations were observed in the results of different preclinical studies on individual ASMs, highlighting the need to standardize animal study methodologies to enhance reproducibility and reduce variation.

01 May 2024·Coronary artery disease

Sacubitril/valsartan improves the prognosis of acute myocardial infarction: a meta-analysis

Article

Author: Wang, Fang ; Zhang, Xuezheng ; Li, Chengde

Objective:

To systematically evaluate the effect of sacubitril/valsartan (SV) on the prognosis of patients with acute myocardial infarction (AMI), and to provide evidence for expanding the clinical application of SV.

Methods:

PubMed, EMbase, Web of Science, and Cochrane Library were searched from inception to October 2023 for randomized controlled trials (RCTs) of SV in patients with AMI. The article was screened and evaluated by the Cochrane 5.1.0 bias risk assessment tool. RevMan5.3 was used for meta-analysis of the outcome indicators.

Results:

Ten RCTs involving 7230 patients were included. The results showed that SV increased left ventricular eject fraction (MD = 2.86, 95% CI [1.81–3.90], P < 0.00001) and reduced readmission rate (RR = 0.46, 95% CI [0.32–0.68], P < 0.0001), decreased N-terminal pro-brain natriuretic peptide (MD = −477.46, 95% CI [−914.96 to −39.96], P = 0.03), and reduced major adverse cardiovascular and cerebrovascular event (MACCE) (RR = 0.48, 95% CI [0.27–0.85], P = 0.01). There was no significant difference in the rate of adverse reaction (AR) between the trial group and the control group (RR = 0.88, 95% CI [0.60–1.30], P = 0.52).

Conclusion:

SV can effectively improve the prognosis of AMI, prevent complications, and there is no significant difference in safety compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker.

News (Medical) associated with Sodium Valproate

16 Jan 2024

·www.pharmaceutical-technology.com

UK MHRA announces new data flagging potential valproate risks

A new study highlights that 5 out of 100 children born to fathers treated with valproate during conception were diagnosed with a neurodevelopmental disorder. Credit: luchschenF via Shutterstock. A recent study, commissioned by the European Medicines Agency, has raised flags regarding potential heightened risks of neurodevelopmental disorders in children fathered by men on valproate around conception. The study indicates that approximately five out of 100 children born to fathers treated with valproate during conception were diagnosed with a neurodevelopmental disorder, in contrast to three out of 100 children whose fathers were on Lamictal (lamotrigine) or Keppra (levetiracetam), two other anti-seizure medicines. The study was resubmitted in August after the trial sponsor, Sanofi , revealed errors that could impact the results. The regulatory authorities are scrutinising the revised study results with forthcoming guidance for patients and healthcare professionals in the pipeline from the Commission on Human Medicines. UK regulators initially recommended strengthened safety measures for valproate, setting them for implementation in January 2024. These measures include restrictions on initiating valproate in new patients under the age of 55 unless there are no other effective treatments or compelling reasons to justify its use. The UK Medicines and Healthcare products Regulatory Agency (MHRA) published guidance in October 2023, introducing original pack dispensing on medicines containing valproate, informing patients about the risks to an unborn baby. Sanofi’s Depakine (sodium valproate) is a drug used to treat conditions such as epilepsy, migraine, and bi-polar disorder. The drug works by affecting certain neurotransmitters in the brain, helping to control seizures. The drug has been linked to an increased risk of birth defects and developmental issues in children when taken by pregnant individuals. In May 2022, a French court ordered Sanofi to pay more than $400,000 in damages to a family that were not made aware about the potential for birth defects related to its drug Depakine. The case involved a child whose autism was said to be linked to the mother taking the drug during pregnancy. The court ruled Sanofi at fault due to inadequate labelling information for Depakine. In 2020, Sanofi was hit with a formal investigation regarding manslaughter charges for the death of four babies, whose mothers took Depakine during their pregnancies. The company denied the charges at the time and said it would challenge the findings of the investigation.

Clinical ResultPatent Infringement

12 Dec 2023

·www.fiercepharma.com

After leak of neurotoxin, Sanofi plant in France is under scrutiny again

A Sanofi plant in France, which was closed down in 2018 for emitting a dangerous neurotoxin, is under scrutiny again after a leak last month. A Sanofi manufacturing facility in France, which was temporarily closed five years ago for emitting dangerous emissions, is under the microscope again after a recent leak caused the release of the same neurotoxin, bromopropane. The plant, which produces epilepsy drug Depakine (sodium valproate), released 75 times the allowable amount of bromopropane in mid-November, according to a report in the French news outlet Le Monde. The facility, located in Mourenx, stopped production “immediately" after noting “inconsistent measurements” of bromopropane emissions, according to a Sanofi spokesperson. “We quickly identified that this isolated and very brief event was linked to the degradation of the treatment unit’s activated carbons following the bad weather and heavy rains that had affected the region in the preceding days,” Sanofi said. “The coals were replaced and bromopropane emissions returned to normal, enabling production to resume after approval from the authorities.” Bromopropane—which is used in the production of Depakine—is classified as a possible carcinogen by the World Health Organization. Manufacturers using bromopropane are required to self-monitor their emissions of the neurotoxin. The drug itself, Depakine, has been under the microscope in France for years. In 2020, France launched an investigation into alleged safety risks for babies when valproate is taken by pregnant mothers. The company has denied the charges. Last month, Le Monde reported that a woman in France, who never took Depakine but has worked next door to the plant since 2011, filed a complaint against Sanofi, saying that her two epileptic children—who were born in 2014 and 2016—have disorders similar to those shown in children whose mothers took the drug during pregnancy. In 2018, after the plant was shut down, French officials continued their scrutiny of the Mourenx facility. In August 2022, a public health investigation was launched, ramping up pressure on the site to remain compliant.

Clinical StudyDrug Approval

07 Nov 2023

·www.fiercepharma.com

Sanofi stands behind 'accuracy of our accounts' amid reports of French manipulation probe

The investigation was first reported by French news outlet La Lettre. Since launching the Regeneron-partnered antibody Dupixent in 2017, Sanofi has relied on the star medicine for sales growth. Now, though, an investigation in France calls into question some of the company's prior financial communications about the launch, according to press reports. According to French publication La Lettre, France’s economic crime authority in March opened a preliminary probe into the company. The case centers on "financial communication" around the launch of Dupixent, according to the publication. Financial news outlet CNBC said it confirmed the probe with a "judicial source." The publication reports that the investigation centers on "possible market manipulation." For its part, Sanofi says it has “not been contacted” in relation to any preliminary investigation by the Parquet National Financier, the company told Fierce Pharma. “We stand by the accuracy of our accounts. As a listed company, the financial information published by Sanofi is duly audited by two auditing firms. Sanofi reserves the right to take legal action against any false or defamatory allegations,” the statement continued. When Sanofi debuted its Regeneron-partnered Dupixent in its first indication in atopic dermatitis, the company pegged expected sales to land in the $3 billion-plus range across several future other uses. These days, the drug is charted to surpass the $20 billion mark later this decade if approved in chronic obstructive pulmonary disease (COPD), analysts at Evercore ISI said in March. With a label that now includes several diseases beyond atopic dermatitis, Dupixent is showing no signs of slowing. Last year, the drug generated full-year sales of $8.7 billion, good for 40% growth from the previous year. Meanwhile, this reported investigation isn't the first time that Sanofi has faced legal scrutiny from officials in its home country. After years of probing potential birth defects tied to its epilepsy medicine Depakine, the case moved forward in 2020 on a manslaughter charge.

Patent Infringement

100 Deals associated with Sodium Valproate

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	N03AG01	-

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Epilepsies, Partial	US	AbbVie, Inc.	30 Dec 1996
Epilepsy, Absence	US	AbbVie, Inc.	30 Dec 1996
Nervous System Diseases	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	01 Jan 1982
Bipolar Disorder	JP	Sumitomo Pharma Co., Ltd.	01 Sep 1981
Migraine Disorders	JP	Sumitomo Pharma Co., Ltd.	01 Sep 1981
Epilepsy	JP	Kyowa Kirin Co., Ltd.	24 May 1974

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EADV 12023 \| EADV 22023	Not Applicable	Alopecia Areata beta catenin	66	Topical Sodium Valproate (SV) -loaded nanospanlastics	umwqnunwdl(cmiltavxbm) = Baseline beta catenin was found to significantly negatively correlate with improvement in the representative patch in patients with baseline level above 0.42 ng/ml klmdsprtdg (pwakomvybv ) View more	-	11 Oct 2023
				Topical Mometasone Furoate Lotion
NCT04698525 (CTgov)	Phase 3	Migraine Disorders	33	Valproate Sodium (Valproate Group)	kgjqhdxsab(fuwtokgsqg) = zygndjheta hefjwqqcwi (lbcagihmxp, lmwtbkhisu - tuhdmnfoqk) View more	-	17 May 2023
				memantine (Memantine)	kgjqhdxsab(fuwtokgsqg) = gzfygctszl hefjwqqcwi (lbcagihmxp, osyptcttir - dgmavcpbij) View more
CTRI/2020/01/022781 (ESMO_ASIA2022)	Phase 2	Platinum-Resistant Ovarian Carcinoma	27	Oral etoposide + Sodium valproic acid (VPA)	vcfaukvlma(ckgyzimynd) = pmrbonofyn aiwmancvrh (dhrdaozdez ) View more	-	03 Dec 2022
NCT01622439 (VALFRID, Pubmed) Manual	Phase 1	Diffuse Large B-Cell Lymphoma First line	-	CHOP+rituximab+Valproate	ifaqwlshtt(ufevburusp) = Valproate（60 mg/kg per day） rubnrsdcyo (idrwwrdkdh ) View more	Positive	26 Jun 2018
IRCT201202199014N1 (Pubmed \| J Biol Chem)	Phase 3	Migraine Disorders	104	Intravenous sodium valproate	wsfzjnzrxe(belihbtrjt) = niyuhulnub uftqnrswjx (dmjurpxahl )	-	01 Jan 2015
				Intravenous dexamethasone	wsfzjnzrxe(belihbtrjt) = cvhzytyuvq uftqnrswjx (dmjurpxahl )
NCT00203242 (CTgov)	Not Applicable	Cluster Headache	15	Depakote+Depacon IV	aishvhfjqo(majowqlebt) = vykjjhzqdh lqunpavgpc (kjxldvdsin, fhyycptolb - woartspjdz) View more	-	06 Jul 2011

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