[Translation] A single-center, randomized, open-label, single-dose (fasting/postprandial), two-formulation, two-sequence, two-period, crossover bioequivalence study of metformin and glibenclamide tablets in healthy Chinese subjects

主要目的：观察中国健康受试者在空腹/餐后状态下单次口服受试制剂二甲双胍格列本脲片（规格：500mg/2.5mg）和参比制剂二甲双胍格列本脲片（商品名：Glucovance®；规格：500mg/2.5mg；持证商：Merck SANTE S.A.S）后的药代动力学特征，评价两种制剂在空腹/餐后状态下的生物等效性。次要目的：观察受试制剂二甲双胍格列本脲片和参比制剂二甲双胍格列本脲片（Glucovance®）在中国健康受试者中的安全性。

[Translation]

Primary objective: To observe the pharmacokinetic characteristics of the test preparation metformin glibenclamide tablets (specification: 500mg/2.5mg) and the reference preparation metformin glibenclamide tablets (trade name: Glucovance®; specification: 500mg/2.5mg; licensee: Merck SANTE S.A.S) after a single oral administration in the fasting/postprandial state in healthy Chinese subjects, and to evaluate the bioequivalence of the two preparations in the fasting/postprandial state. Secondary objective: To observe the safety of the test preparation metformin glibenclamide tablets and the reference preparation metformin glibenclamide tablets (Glucovance®) in healthy Chinese subjects.

Start Date18 Nov 2023

Sponsor / Collaborator

Tonghua Wantong Pharmaceutical Co. Ltd.

NCT04930744

/ RecruitingPhase 2IIT

A Prospective, Randomized Open-Label Phase II Study of the Safety and Tolerability of Metformin in Combination With Standard Antimicrobial Treatment of Pulmonary Tuberculosis in People With TB and Co-infected With HIV

The METHOD study will examine whether adding metformin to standard antibiotic treatment for tuberculosis (TB) in people with HIV is safe and well tolerated. The study will also test if adding metformin clears the infection more quickly and with less lung damage. When enrolled, participants will have an equal chance of being in the group that takes standard TB medicines alone or in the group that also takes metformin. Participants will have a chance to be put on either: 1) standard TB medicines (isoniazid, rifampicin, ethambutol and pyrazinamide for two months, continuing isoniazid and rifampin for four more months) only; or 2) the same standard TB medicines plus metformin. Participants randomized to the metformin arm will take metformin for eleven weeks, starting one week after starting the standard TB medicines. In addition to monitoring for side effects, all participants will have studies of drug levels and lung and immune function.

Start Date26 Aug 2021

Sponsor / Collaborator

University of Massachusetts

[+4]

CTR20211771

/ CompletedNot Applicable

三门峡赛诺维制药有限公司生产的二甲双胍格列本脲片（Ⅱ）（500 mg/5 mg）与Merk SANTE S.A.S 持证的二甲双胍格列本脲片（商品名：GlucovanceTM，500 mg/5 mg）在健康受试者中的单次给药、随机、开放、两周期、双交叉、空腹及餐后状态下的生物等效性研究

[Translation] A single-dose, randomized, open-label, two-period, double-crossover, fasting and fed bioequivalence study of metformin glibenclamide tablets (II) (500 mg/5 mg) produced by Sanmenxia Sanowei Pharmaceutical Co., Ltd. and metformin glibenclamide tablets (trade name: GlucovanceTM, 500 mg/5 mg) certified by Merk SANTE S.A.S in healthy subjects

主要研究目的：以 Merk SANTE S.A.S 持证的二甲双胍格列本脲片（商品名：GlucovanceTM）为参比制剂，以三门峡赛诺维制药有限公司生产的二甲双胍格列本脲片（Ⅱ）为受试制剂，通过单中心、随机、开放、单次给药、两周期、双交叉临床研究来评价两种制剂的人体生物等效性。次要研究目的：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]

The main purpose of the study is to use the certified metformin glibenclamide tablets (trade name: GlucovanceTM) of Merk SANTE S.A.S as the reference preparation and the metformin glibenclamide tablets (II) produced by Sanmenxia Sanowei Pharmaceutical Co., Ltd. as the test preparation to evaluate the bioequivalence of the two preparations in humans through a single-center, randomized, open, single-dose, two-cycle, double-crossover clinical study. Secondary purpose of the study: to observe the safety of the test preparation and the reference preparation in healthy Chinese subjects.

Start Date11 Aug 2021

Sponsor / Collaborator

Sanmenxia Sinovi Pharmaceutical Co., Ltd.

100 Clinical Results associated with Glyburide/Metformin Hydrochloride

100 Translational Medicine associated with Glyburide/Metformin Hydrochloride

100 Patents (Medical) associated with Glyburide/Metformin Hydrochloride

Literatures (Medical) associated with Glyburide/Metformin Hydrochloride

01 May 2023·Clinical Pharmacology in Drug Development

Pharmacokinetic and Bioequivalence Studies of 2 Metformin Glibenclamide Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions

Article

Author: Chen, Lin ; Huang, Jiao ; Huang, Xiaolun ; Li, Xinjing

AbstractThe rational combination of oral antidiabetic agents is more likely to provide better glycemic control than monotherapy. Metformin glibenclamide tablets can be used as second‐line therapy for patients with type 2 diabetes mellitus who cannot successfully control their blood glucose levels by diet and exercise plus metformin or sulfonylureas. The aim of this study was to evaluate the bioequivalence and safety of metformin hydrochloride and glibenclamide tablets (500 mg/5 mg) prepared by 2 different vendors in healthy Chinese subjects under fasting and fed conditions. This is an open‐label, single‐center, randomized, 2‐formulation, 2‐period crossover study. After screening, 40 subjects were enrolled in the fasting trial, while 40 subjects were enrolled in the fed trial. Qualified subjects were randomly assigned to receive a monotherapy dose of 500 mg/5 mg of the test or reference formulation, and after a 1‐week washout period, they took the alternative formulation. Blood samples were collected from 24 blood collection sites per cycle for pharmacokinetic analysis until 36 hours after oral administration. In total, 78 subjects completed the study. Under fasting and fed conditions, the geometric mean ratios of maximum plasma concentration, area under the plasma concentration–time curve (AUC) from time 0 to time of last quantifiable drug level , and AUC from time 0 to infinity between the 2 products, as well as the corresponding 90%CIs, were all within the range of 80%–125%. It was found that exposure (AUC from time 0 to infinity) to metformin is decreased by about 25% in the fed state compared to fasting, whereas glibenclamide exposure is increased by about 30% in the fed state. No severe adverse events were observed in the study.

17 Feb 2022·BiomarkersQ4 · MEDICINE

Ameliorative effect of flavonoid-rich extracts from Gongronema latifolium against diabetic cardiomyopathy via serpin A₃ and socs3-a in streptozocin treated rats

Q4 · MEDICINE

Article

Author: Omotuyi, Olaposi Idowu ; Brai, Bartholomew I. C. ; Johnson, Oluwafolakemi ; Ajiboye, Basiru Olaitan ; Ejeje, Jerius Nkwuda ; Owolabi, Olutunmise Victoria ; Oyinloye, Babatunji Emmanuel

INTRODUCTIONThe present study access the effect of the flavonoid-rich extract from Gongronema latifolium against cardiomyopathy streptozotocin-induced diabetic rats.MATERIALS AND METHODSThe flavonoid-rich extract from G. latifolium leaf (FREGL) was prepared using a standard method. Diabetes was induced by a single intraperitoneal (i.p.) injection of streptozotocin. The experimental animals were divided into five groups as non-diabetic rats, diabetic control, diabetic rats administered low and high doses of FREGL (13 and 26 mg/kg), and metformin-glibenclamide orally for 21 days. Hence, the experimental animals were sacrificed; blood and heart were harvested to determine diverse biochemical parameters, including the gene expressions of serpin A₃ and socs3-a as well as histological examination.RESULTSThe results demonstrated that FREGL significantly (p < 0.05) reduced fasting blood glucose, total cholesterol, low density lipoprotein (LDL), triglyceride (TG), lipid peroxidation levels, as well as the activities of lactate dehydrogenase and creatine kinase-MB, including the relative gene expressions of serpin A₃ and Socs3-A in diabetic rats. Also, diabetic rats that received different doses of FREGL showed a substantial rise in insulin and high density lipoprotein (HDL) levels, antioxidant enzyme activities, as well as, normal histoarchitecture of the heart tissues.CONCLUSIONTherefore, FREGL may be beneficial in alleviating diabetic cardiomyopathy.

01 Jan 2022·European Journal of Pharmaceutical SciencesQ2 · MEDICINE

NDMA analytics in metformin products: Comparison of methods and pitfalls

Q2 · MEDICINE

Article

Author: Kirsch, Annette ; Barrau, Elodie ; Baranowski, Romane ; Goettsche, Anja ; Blom, Giorgio ; O'Neill, Nicholas ; Bristow, Tony ; Seegel, Maic ; Reifenberg, Philipp ; Keitel, Judith ; Schlingemann, Joerg ; Fritzsche, Matthias ; Krueger, Phillip ; Desmartin, Emmanuel ; Harrison, Mark ; Guessregen, Brunhilde ; Mouton, Bruno ; Leicht, Stefan ; Hickert, Sebastian ; Cimelli, Alexandra ; Saal, Christoph

BACKGROUNDFor nearly three years, the concerns regarding trace levels of N-nitrosamines in pharmaceuticals and the associated cancer risk have significantly expanded and are a major issue facing the global pharmaceutical industry. N-nitrosodimethylamine (NDMA) found in formulations of the popular anti-diabetic drug metformin is a prominent example. This has resulted in product recalls raising the profile within the media. Issues of method robustness, sample preparation and several unexpected sources of nitrosamine contamination have been highlighted as false positive risks. It has become apparent that the identification of the root causes of artefactual formation of nitrosamines must be identified to mitigate risk associated with the analysis.METHODSA comparison study between four laboratories, across three companies was designed, employing orthogonal mass spectrometric methods for the quantification of NDMA in two metformin immediate release (IR) formulations and one extended release (XR) formulation. These were 2x LC-MS/MS, GC-MS/MS and GC-HRMS.RESULTSGood agreement of results was obtained for the IR formulations. However, we measured higher concentrations of NDMA in the XR formulation using GC-MS/MS compared to LC-MS/MS. We could show that this was due to artefactual (in situ) formation of NDMA when samples were extracted with dichloromethane. Removal of dimethylamine (DMA) and nitrite from the extracted sample or the addition of a nitrosation scavenger are shown to be effective remedies. NDMA in situ formation was not observed in 10% MeOH or acetonitrile.CONCLUSIONMetformin pharmaceuticals contain traces of the API impurity DMA as well as inorganic nitrite from excipients. This can lead to artefactual formation of NDMA and hence false positive results if DCM is used for sample extraction. Similar artefacts are likely also in other pharmaceuticals if these contain the secondary amine precursor of the respective nitrosamine analyte.

100 Deals associated with Glyburide/Metformin Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	A10BD02	-

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Mellitus	Australia	Alphapharm Pty Ltd.	05 Aug 2004
Diabetes Mellitus, Type 2	China	Shanxi Aoxun Medicine Co., Ltd.	01 Jan 2001

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00836472 (CTgov)	Phase 1	-	60	Glyburide/Metformin 5 mg/500 mg Tablets (Glyburide Metformin)	eughyzuvyf(rmobeelghh) = xxqgkpwojs nsuovqyepp (ztxhjuwyra, ukaywxjifv - exdcgjtjky) View more	-	04 Aug 2009
				Glucovance® 5 mg/500 mg Tablets (Glucovance®)	eughyzuvyf(rmobeelghh) = rjfcqdooxm nsuovqyepp (ztxhjuwyra, ttsgjhbgwl - hpcbgpzvjm) View more
NCT00835991 (CTgov)	Phase 1	-	60	Glyburide/Metformin 5 mg/500 mg Tablets (Glyburide Metformin)	qszcaaymee(uikhmlouvm) = nwjpcwvjyn zfxwdppzvo (ttmrlvbddo, ykdlzztaxt - zltjpkmejw) View more	-	04 Aug 2009
				Glucovance® 5 mg/500 mg Tablets (Glucovance®)	qszcaaymee(uikhmlouvm) = mywktwtccu zfxwdppzvo (ttmrlvbddo, huihitorip - jfwymitfxc) View more

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