Original Brand Research Articles

Should Global Brands Engage in Brand Activism?

Brand activism, taking a stance on current and divisive sociopolitical issues, has emerged as a novel means of expressing a brand's values and engaging with the firm's customer base. Yet, globally, companies lack conclusive guidance on the consequences of taking a stance. This research asks a novel question: Should global brands engage in activism? Using varying activism manipulations (e.g., statements and actions), five studies reveal consumer preference for activist global brands. More importantly, guided by schema change theory, the authors find that the positive brand activism effect is particularly strong for global brands associated with negative brand origin, irrespective of consumers’ prior attitude valence. However, brands with positive origin associations benefit from activism only when consumers’ prior attitude valence is in alignment. The authors also identify the mediating effects of self–brand connection, which has downstream consequences for behavioral intentions. Taken together, this work sheds new light on consumer perceptions of brand activism across cultures, elucidates why consumers prefer global brands that engage in activism, and offers actionable insights for global brand managers.

Cooperation mode selection strategies in platform ecosystems: analyzing brand value, cross-selling, and platform empowerment

Purpose This paper aims to investigate the vertical cooperative relationship between the core enterprise and the manufacturer within the platform ecosystem, specifically analyzing the optimal decision-making processes of both parties under the original equipment manufacturer (OEM) and original brand manufacturer (OBM) modes. Design/methodology/approach This paper uses game theory to analyze the problem, considering factors such as brand value difference, cross-selling and platform empowerment. It constructs the game models for both OEM and OBM modes and discusses the selection strategies for the cooperation mode. Findings The results indicate that the choice of cooperation mode by the manufacturer and the core enterprise depends on the relative size of their brand values. In cases of inconsistent choices, cooperation can be improved by designing a transfer payment contract. When the brand value is constant, the product price is comprehensively affected by cross-selling revenue, price elasticity coefficient, cost coefficient of sales effort and cost coefficient of platform empowerment. The enterprise reduces the price only when the potential revenue brought by increasing product sales exceeds the marginal profit brought by increasing product pricing; otherwise, it raises the sales price. Originality/value The platform ecosystem is emerging as a future direction for business mode development. However, there is a paucity of research on the cooperation modes between manufacturers and core enterprises within the platform ecosystem.

HR-brand: features of formation and development

Relevance. The development of HR management stems from the need for organizations to attract and retain highly qualified employees in the competitive environment of the modern labor market. HR branding is a strategy based on the formation and support of a positive image of the company in the eyes of employees, as well as the company's commitment to the principles and values that bind employees and the organization. Positive evaluations of the organization's employees and their recommendations can attract new specialists and strengthen the company's reputation as a reliable and attractive employer.The purpose of the article is to study a special category of reputation and perception of the company – the HR brand.Objectives: to study the conditions for building an HR brand, its structure and key elements; to consider the history of the origin of the idea of HR branding; to assess the interest in creating a special reputation in the field of human resource management; to justify why it is impossible to build an EVP (employer's value proposition) without HR branding.Methodology. In the course of scientific research, empirical, theoretical, statistical methods and methods of graphical representation were used.Results: the theoretical aspects of building a company's HR brand were studied; the popularity of this topic in science and business was shown. A set of knowledge about the features of HR branding in the Russian and foreign markets has been formed and the prospects for the development of this area are shown. It shows why it is important to work on an HR brand and how to start forming a positive image of the company, its reputation and prestige.Conclusions. The article emphasizes the relevance and importance of the topic under consideration, taking into account the latest trends, prerequisites and prospects for new companies. The possibilities that open up for an employer when forming an original and popular HR brand are considered.

Relationship between Prices and Quality of Essential Medicines from Different Manufacturers Collected in Cameroon, the Democratic Republic of the Congo, and Nigeria.

Achieving universal access to affordable medicines and at the same time ensuring the quality of medicines presents a challenge, especially in low- and middle-income countries. Here, the relationship between medicine prices and medicine quality was investigated in three African countries. From different types of health facilities and medicine vendors, 711 samples of 18 different essential medicines were purchased and analyzed for quality (assay and dissolution) according to the United States Pharmacopeia. Without exception, all originator brand medicines and all SRA generics (generic medicines manufactured in countries with stringent regulatory authorities [SRAs]) complied with pharmacopeial specifications. In contrast, 21.1% of the non-SRA generics (manufactured in countries without SRAs) were substandard. The median prices of originator brands and SRA generics were three times and two times higher than those of non-SRA generics, respectively. Within the non-SRA generics, no positive correlation was observed between medicine quality and medicine price. Medicines manufactured in India, China, or African countries showed similar quality and similar prices. Only a single WHO-prequalified medicine sample was found among the 711 samples. Non-SRA generic medicines produced by manufacturers for which WHO had published Public Inspection Reports showed a significantly lower rate of substandard medicines (7.3%) and, at the same time, significantly lower prices (by 33%) than other non-SRA generics. Falsified medicines (total 2.0%) were found among all categories of medicines and had prices similar to those of non-SRA generics. Our findings indicate that adequate quality assurance does not necessarily imply an increase in medicine prices.

Comparison of the efficacy of a generic plerixafor versus Mozobil as adjunct peripheral blood stem cell mobilization agents in multiple myeloma patients.

Plerixafor is an adjunct peripheral blood stem cell (PBSC) mobilization agent with well-demonstrated safety and efficacy. The routine use of the originator brand drug (Mozobil) has been limited by cost. This retrospective study was conducted to compare the mobilization efficacy of a lower-cost generic plerixafor and Mozobil in multiple myeloma (MM) patients. The study included two near-concurrent cohorts of MM patients mobilized with brand (n = 64) or generic (n = 61) plerixafor in addition to filgrastim. Collection and early engraftment outcomes were compared. The two cohorts had comparable distributions of sex, age, and weight. Previous treatment histories and proportions of upfront versus just-in-time plerixafor use were similar. There was no significant difference in their median overall cumulative total yield (106 CD34+ cells/kg) (brand, 5.91; generic, 5.80; p = .51). However, the generic cohort had a significantly higher median yield after the first dose (4.79 vs. 3.78, p = .03), and consequently lower median numbers of plerixafor doses (p = .001) and collection days (p = .002). Only 31.1% of patients in the generic arm required more than one dose versus 59.4% of patients in the brand arm (p = .006). All transplanted patients in the brand and generic arms (90.6% and 85.2% respectively, p = .42) achieved engraftment. There was no significant difference in their median times to platelet and neutrophil engraftment, nor their transfusion requirements during the first 30 days post-transplant. The generic plerixafor produced comparable cumulative collection yields and early engraftment outcomes as Mozobil, but fewer doses and collection days were needed to reach collection goal.

Availability and affordability of selected medicines in the Islamic Republic of Iran

Background: There is a standard methodology for measuring and evaluating the availability and affordability of selected medicines in the healthcare system, especially in low- and middle-income countries. Aim: To investigate availability, affordability and accessibility of medicines in the Islamic Republic of Iran in 2021 and compare the results with those from 2019. Methods: This descriptive cross-sectional study investigated the availability and affordability of 60 selected medicines in Islamic Republic of Iran. Availability and affordability were measured using the WHO/Health Action International methodology. Results: The availability rates for originator brands in the public, private and other sectors were 6.4%, 8.6% and 6.8%, respectively. In contrast, availability rates for lowest-priced and most-sold generics were 44.7% and 63.6% in the public sector, 45.4% and 66.4% in the private sector, and 39.6% and 58.6% in other sectors. Only 20.0% of originator brands in the Islamic Republic of Iran were affordable, while 96.6% of the lowest priced and 95.0% of the most sold generics were affordable. Conclusion: Most medicines in the Islamic Republic of Iran were affordable and the pharmaceutical supply chain was acceptable.

Brand and Country of Origin Towards Consumer Attitudes in Choosing Smartphones

As technology advances, smartphone devices become a fascinating topic for conversation. The growth of multiple smartphone brands as choices appears to be inextricably linked to the relevance of customer attitudes in deciding which smartphone to use. The growth of multiple smartphone brands as choices appears to be inextricably linked to the relevance of customer attitudes in deciding which smartphone to use. Furthermore, when choosing a smartphone, shoppers consider the product's nation of origin. This study uses a quantitative approach method. Involving the 100-person Dumai City community. The findings of the partial analysis indicate that brands have a positive and significant effect on consumer attitudes and country of origin variables have a positive but not significant effect on consumer attitudes. Brand and country of origin together have a positive and significant effect on consumer attitudes in the Dumai City community. The result of the Determination Coefficient is 21.3%, with the remaining 78.7% impacted by other variables.

Rapid discriminant analysis for the origin of specialty yam based on multispectral data fusion strategies

In order to achieve rapid and effective identification of Hebei yam, a qualitative discrimination model was constructed based on near infrared (NIR), mid infrared (MIR), and microscopic Raman spectra in combination with individual spectra and multispectral data fusion strategies. The results showed that the gray wolf optimizer-support vector machine (GWO-SVM) model constructed by mid-level fusion using the three feature spectra performed the best in distinguishing the geographic origin of the yam, with a prediction accuracy of 100.00% in both the training set and the test set, and an F1 score of 1.00. The results indicated that due to spectral complementarity, NIR, MIR and Raman combined with feature-level fusion can be used as a powerful, non-destructive, fast and feasible tool for geographic origin classification and brand protection of Hebei yam. This work is expected to be a potential method for origin identification analysis and quality monitoring in the food and pharmaceutical industries.

Being a member of global community: the effect of Chinese brand origin salience on global identity perceptions and brand evaluations

PurposeGiven that Chinese brands and products are widespread in the global market, this paper aims to examine the effect of Chinese brand origin salience (vs not) on brand evaluations by increasing global identity perceptions, and figuring out the moderating role of uncertainty avoidance.Design/methodology/approachThree experiments were conducted in different product categories to test the effect of Chinese brand origin salience. Study 1 and Study 2 collected data from different countries (i.e. Japan and the USA) with varying levels of uncertainty avoidance. In Study 3, the data were collected from the single-country sample, including participants from cultural backgrounds with high (Asian Americans) and low (Caucasian Americans) uncertainty avoidance.FindingsChinese brand origin salience positively influences brand evaluations via increased global identity perceptions. In addition, uncertainty avoidance plays a moderating role in the process. Specifically, the favorable effect of Chinese brand origin salience on brand evaluations will be attenuated among consumers with high (vs low) uncertainty avoidance.Originality/valueThis paper demonstrates that Chinese brand origin salience can enhance brand evaluations beyond prior work focusing on the negative stereotypes of Chinese brands and their imitation of Western brands. Importantly, Chinese brands have become an important part of the global community as Chinese brand origin salience can evoke consumers’ global identity.

Access to essential and innovative anti-cancer medicines: a longitudinal study in Nanjing, China

PurposeTo evaluate the availability, cost, affordability of anti-cancer medicines in Nanjing, Jiangsu.MethodsA longitudinal tracking investigation study was performed to collect information about 24 essential anti-cancer medicines (EAMs) and 17 innovative anti-cancer medicines (IAMs) in 26 healthcare institutions in Nanjing from 2016 to 2020. The availability, cost, drug utilization and affordability of EAMs and IAMs were investigated.ResultsThe availability of EAMs showed no significant changes in Nanjing, but the availability of IAMs showed a significant increase in 2018 and 2019 and tended to stabilize in 2020. For EAMs, the DDDc(Defined Daily Dose cost) of LPGs (Lowest-Priced Generics) showed no significant changes, and the DDDc of OBs (Originator Brands) and IAMs significantly decreased. The DDDs(Defined Daily Doses) of EAMs (LPGs) showed a decreasing trend since 2016 and rose again in 2019. Overall, the DDDs of EAMs (LPGs) decreased by 25.18% between 2016 and 2020, but the proportion selected for clinical treatment remained at 67.35% in 2020. The DDDs of EAMs (OBs) and IAMs both showed an increasing trend year by year, with a proportional increase of 207.72% and 652.68%, respectively; but the proportion selected for clinical treatment was only 16.09% and 16.56% respectively in 2020. EAMs (LPGs) had good affordability for urban residents but poor affordability for rural residents; the affordability of EAMs (OBs) and IAMs was poor for both urban and rural residents.ConclusionsThere were no significant changes in the availability and cost of EAMs (LPGs), whose lower prices showed better affordability. Although their relative change in drug utilization showed a decreasing trend, they still dominated clinical treatment. Driven by the national drug price negotiation (NDPN) policy, the availability of IAMs was on the rise. It is necessary to further develop and strengthen policies for essential medicines procurement assessment to improve the accessibility of EAMs.

P-765 Minding the sweet spot in birth weight: Metformin and insulin versus no treatment

Abstract Study question Is the use of metformin or insulin associated with an increased risk of large or small for gestational age birth in comparison to drug-naïve GDM? Summary answer No difference in SGA / LGA odds with drug-naïve mothers versus metformin-exposed, but higher odds of SGA and lover odds of LGA compared to insulin-exposed. What is known already In Europe, the originator brand of metformin has received a label update allowing the use during pregnancy. Use of metformin during pregnancy is associated with a reduced risk of LGA, but increased risk of SGA birth compared to insulin. In CLUE, metformin only exposure demonstrated a reduced odds of LGA birth (weighted OR (wOR) 0.82, 95% CI 0.67 to 0.99), but increased risk for SGA (wOR 1.65, 95% CI 1.16 to 2.34). Insulin use during a hyperglycemic pregnancy is discussed to increase birth weight. Study design, size, duration This was a follow-up study performed on our previously published population-based register data cohort study CLUE with maternal exposure to metformin, insulin or diagnosed with GDM but drug-naïve until birth. The follow-up study included 3,964 subjects in the metformin only cohort, 5,273 in the insulin only cohort and 82,675 women diagnosed with GDM but without drug treatment during the respective pregnancy (naïve cohort). Participants/materials, setting, methods The study population included singleton children born to 18-45 year old women from Finland during 2004–2016. Exclusion criteria were maternal type 1 diabetes, exposure to glucocorticoids and antidiabetic medications except metformin and insulin during the respective pregnancy. Analyses of SGA and LGA used logistic regression to estimate ORs with 95%CIs, with naïve cohort as the reference. Inverse probability of treatment weighting (IPTW) with stabilized weights based on propensity scores (PS) was used to control for confounding. Main results and the role of chance The odds of SGA birth were significantly higher in the naïve cohort (wOR 1.41, 95% CI 1.11 to 1.79) compared to those exposed to insulin, and the odds for LGA birth were significantly lower (wOR 0.72, 95% CI 0.64 to 0.82). No difference was found in the odds for SGA or LGA when the metformin cohort was compared with naïve cohort (wOR 0.97, 95% CI 0.73 to 1.27 and wOR 0.91, 95% CI 0.75 to 1.11, respectively). Limitations, reasons for caution Drug exposure was assessed on the dispensed drug only. and not intake, also prohibiting dose and treatment duration stratification. Although IPTW methods were used to account for many characteristics, the prevalence of underlying diseases differed across treatment cohorts, the naïve cohort which was defined by indication and absence of treatment. Wider implications of the findings This analysis adds to the growing evidence that insulin exposure in pregnancy may increase the risk of LGA, which is associated with increased adult obesity. Metformin did not increase the odds of SGA or LGA. Metformin may be considered a reasonable treatment during pregnancy, e.g. at risk for LGA birth. Trial registration number not applicable

Combating lookalike product through adapting advertising appeals to consumer value: Strategic implications to brand imitation management

Abstract“Lookalike” products, including counterfeits and copycats, are increasingly common in today's global marketplace. Four lab experiments were conducted involving 653 participants, and data were analyzed through SPSS 26. Based on social representation (SR) theory and self‐construal theory, this research examines how advertising for original brands impacts purchase intent for counterfeits and copycats differently. The results suggest that ads for the original product using value‐expressive (vs. utilitarian) appeals result in lower intent to purchase copycat versions. However, ads for the original product using utilitarian (vs. value‐expressive) appeals lead to lower purchase intent for counterfeit versions. The results also show that consumer need fulfillment mediates the interactive effect between ad appeal type and product type. The current research provides useful insights for marketers or retailers grappling with ongoing competitive threats posed by lookalike products and underscores the strategic utilization of various advertising tactics to reduce the demand for copycats and counterfeits.

Impact of Brand on Consumer Psychology: A Case Study

The paper deals with the results of the primary research which purpose was to examine the impact of brand on influencing consumers to purchase a product. The goal of the paper is to stress the fact that the brand has an impact on customer decision-making process. Original primary data within the primary research were collected by using a quantitative method of questionnaire. Into the quantitative research was involved selected group of 1,250 respondents. Partial results of the complex research conducted between 2009 and 2014 are subject to the content of the paper. Primary research was conducted continuously during the period of six months in 2014 in Slovakia. An established questionnaire was pilot tested and revised before it was used. As the statistical method was used chi-square test. Based on above stated subject area of research have been formulated two hypotheses focused on relationship between the age of respondents and purchasing branded products and between the age of respondents and brand preference. We have found that purchasing of branded products and preference of brand origin depends on the age of consumers. Keywords: Consumer psychology, brand image, Consumer behaviour toward product, brand image in consumer mind.

Stable isotope profiling of cigarettes assisted with chemometrics for authenticity determination

The battle against tobacco fraud presents a formidable challenge, given the global proliferation of imitation and counterfeit cigarettes. This not only inflicts economic losses on governments but also poses significant health risks due to the prevalence of these fraudulent products. This research delves into the application of stable isotopes (δ13C, δ15N, δ2H, and δ18O) and bio-elements (C% and N%) to discern the authenticity of various cigarette brands. Differences in brand origin notably impacted the δ15N and δ2H values. The assessment of cigarette authenticity, as well as the specific brands, unveiled maximum variances in the δ15N and δ2H values, underscoring their potential as robust discriminators between genuine and counterfeit products. Unsupervised Principal Component Analysis results consistently corroborated the authenticity of the samples for the four brands. The integration of chemometric methods, such as Orthogonal Partial Least Squares-Discriminant Analysis, yielded highly accurate authentication for cigarettes across the four brand categories, achieving an accuracy of over 96.8 %. Additionally, this investigation revealed that the critical determinants in distinguishing authentic cigarettes were the isotopic values of δ15N, C%, and δ18O. This work paves the way for a more convenient avenue for the classification of cigarette authenticity compared to untargeted analysis that need to a comprehensive set of chemical fingerprints.

Analysis of the availability of bronchodilators and anti-inflammatory drugs for patients with chronic obstructive pulmonary disease

Background. The study of drug availability for patients with chronic obstructive pulmonary disease (COPD) represents one of the priority tasks in the organization of effective counteraction to COPD in the Russian Federation.Objective: to assess drug prices, affordability, and availability for COPD patients.Material and methods. The analysis of drug availability for COPD patients was carried out according to the methodology of the World Health Organization and Health Action International (WHO/HAI). Bronchodilator and anti-inflammatory therapy of originator brands and lowestpriced generics was evaluated. The consumption volume of the studied drugs was also analyzed using the ATC/DDD (Anatomical Therapeutic Chemical classification / defined daily dose) pharmacoepidemiologic methodology over a three-year period (from 2020 to 2022), taking into account their share of total DDD (drug utilization analysis, DU90%).Results. According to the results of DU90% analysis, the most purchased drugs for bronchodilator and anti-inflammatory therapy for all the years under study were drugs from the groups of short-acting bronchodilators (salbutamol, fenoterol, ipratropium bromide + fenoterol) and inhaled glucocorticoids (budesonide, beclomethasone). The obtained data were confirmed by the results of the physical availability study. Thus, the highest percentage of physical availability was for short-acting inhaled beta-2-agonists (SABA) (salbutamol). Analysis of drug affordability also revealed a tendential superiority of SABA and short-acting anticholinergics over baseline bronchodilators and antiinflammatory drugs.Conclusion. Low affordability of the main drugs of baseline therapy contributes to the burden of COPD and necessitates improvement of drug supply mechanisms for individuals, especially those with low material income, which in the long term will significantly reduce the costs of the healthcare system for the treatment of these patients by decreasing the severity and frequency of exacerbations.

Analysis of Music Brand Similarity Levels Using a Visual Computing Approach

Currently, many trademarks have emerged, especially for music equipment products circulating in the community. Especially in Indonesia, musical instrument brands with various models have emerged. The problem occurs when the brand is considered to resemble the original brand, which makes it uncomfortable for musicians. Even though the quality of the tone produced is not assessed from a brand perspective, it is felt by brand owners to be quite a violation of the code of ethics. This has an impact on marketing products that are considered genuine. In this paper, a concept will be proposed in determining whether a trademark is considered authentic in terms of the logo. Use of Visual Computing with SIFT and SURF algorithms. SIFT (Scale-Invariant Feature Transform) and SURF (Speeded-Up Robust Features) are two popular algorithms for feature extraction and matching in image processing. Both are frequently used in computer vision applications such as object detection, image matching, and object recognition. The results of this analysis will be used for musicians who want to buy musical equipment to be able to detect the logo to compare the success of a musical instrument product. The appropriateness of the quality itself will be discussed in a different discussion. The benefits that can be generated will make musicians, especially in Indonesia, more conscientious. The possibility of sorting so that you can like your own product will be very possible.

Access to essential medicines for diabetes care: availability, price, and affordability in central Ethiopia

BackgroundDiabetes is a major global public health burden. Effective diabetes management is highly dependent on the availability of affordable and quality-assured essential medicines (EMs) which is a challenge especially in low-and-middle-income countries such as Ethiopia. This study aimed to assess the accessibility of EMs used for diabetes care in central Ethiopia’s public and private medicine outlets with respect to availability and affordability parameters. MethodsA cross-sectional study was conducted in 60 selected public and private medicine outlets in central Ethiopia from January to February 2022 using the World Health Organization/Health Action International (WHO/HAI) standard tool to assess access to EMs. We included EMs that lower glucose, blood pressure, and cholesterol as these are all critical for diabetes care. Availability was determined as the percentage of surveyed outlets per sector in which the selected lowest-priced generic (LPG) and originator brand (OB) products were found. The number of days’ wages required by the lowest paid government worker (LPGW) to purchase a one month’s supply of medicines was used to measure affordability while median price was determined to assess patient price and price markup difference between public procurement and retail prices.ResultsAcross all facilities, availability of LPG and OB medicines were 34.6% and 2.5% respectively. Only two glucose-lowering (glibenclamide 5 mg and metformin 500 mg) and two blood pressure-lowering medications (nifedipine 20 mg and hydrochlorothiazide 25 mg) surpassed the WHO’s target of 80% availability. The median price based on the least measurable unit of LPG diabetes EMs was 1.6 ETB (0.033 USD) in public and 4.65 ETB (0.095 USD) in private outlets. The cost of one month’s supply of diabetes EMs was equivalent to 0.3 to 3.1 days wages in public and 1.0 to 11.0 days wages in private outlets, respectively, for a typical LPGW. Thus, 58.8% and 84.6% of LPG diabetes EMs included in the price analysis were unaffordable in private and public outlets, respectively.ConclusionsThere are big gaps in availability and affordability of EMs used for diabetes in central Ethiopia. Policy makers should work to improve access to diabetes EMs. It is recommended to increase government attention to availing affordable EMs for diabetes care including at the primary healthcare levels which are more accessible to the majority of the population. Similar studies are also recommended to be conducted in different parts of Ethiopia.

Access to innovative anticancer medicines in China: a national survey on availability, price and affordability

ObjectivesThis study aimed to investigate the availability, price, and affordability of nationally negotiated innovative anticancer medicines in China.DesignRetrospective observational study based on data from a nationwide medical database.Data sources/settingQuarterly data...

Marketing Failure Case Study — Dolce & Gabbana as an Example

In November 2018, Dolce & Gabbana took to social media to warm up for its fashion week in Shanghai by releasing a controversial video in which Dolce & Gabbana models had extreme difficulty eating Italian food — pizza, cannoli, etc — with chopsticks while the video’s narration used a disgusting tone to explain. The video was released to widespread attention and controversy, as it was deemed to be disrespectful of traditional Chinese culture and racist, causing a huge reaction in China, where Dolce & Gabbana cancelled a fashion show scheduled for Wednesday following a boycott by celebrities and social media users, while retail websites around the country such as Jingdong and Alibaba took down Dolce & Gabbana’s products. On top of this, the situation has been further complicated by negative comments about China by Dolce & Gabbana’s designer Stefano Gabbana, which have been widely circulated online. Pressured by the situation, Dolce & Gabbana apologised and claimed that its accounts had been hacked in an attempt to save the Chinese market with this action, but it did not produce any positive trends. Dolce & Gabbana is a luxury brand of Italian origin, which is widely popular worldwide for its unique designs and baroque Mediterranean style, which is different from other luxury brands. It entered the Chinese market in 2005 and in 2018, it has 44 shops in China alone, while major e-commerce websites sell it. In its financial report for mid-2017-2018, it showed a turnover of €1.3 billion (Glyn Atwal et al.).

Bioequivalence of Related GelShieldⓇ Sustained-release Formulations of Metformin: A Pooled Pharmacokinetic Analysis

PurposeGlucophageⓇ (Merck Healthcare KGaA, Darmstadt, Germany) is the originator brand of metformin hydrochloride, an oral antidiabetic drug. Metformin is recommended in guidelines as first-line treatment of type 2 diabetes mellitus and increasingly in related insulin-resistant conditions, such as prediabetes and polycystic ovary syndrome. The GelShieldⓇ sustained-release formulation tablet of GlucophageⓇ has been improved from the historic version marketed in 2000. Bioequivalence has been demonstrated stepwise along this evolution; however, a head-to-head evaluation between the initial and the current version is missing. This analysis aims to close this gap and to determine bioequivalence between related originator GelShieldⓇ sustained-release formulations of metformin, GlucophageⓇ (GXR 500 mg), from Europe and the United States. MethodsData from seven randomized crossover bioequivalence studies in 361 healthy participants of Asian and non-Asian ethnicity from Europe, the United States, and Asia were considered. All evaluated a single oral dose of 500 mg of the test and reference formulation in healthy male and female participants in fed and fasted state. Bioequivalence was evaluated by means of a combined bridging analysis of available data on the current round tablet from Europe (rGXR EU) and the historic oblong tablet from the United States (oGXR US) in healthy Asian and non-Asian participants under fed and fasting conditions. Bioequivalence between the two formulations was assessed statistically with a mixed effects model for AUC0-t, Cmax, and AUC0-inf. FindingsIn all studies, bioequivalence between the respective test and reference formulations of GXR was shown. Statistical analysis of pooled pharmacokinetic data of 2 (primary pooling set) or 3 studies (secondary pooling set) demonstrated bioequivalence between rGXR EU and oGXR US via bridging with oGXR EU. The 90% CI for the geometric mean ratio of all pharmacokinetic parameters was within the bioequivalence range of 0.80 to 1.25. In the primary pooling set, geometric least squares mean ratios in the fed group ranged from 0.9931 (90% CI, 0.9151–1.0778) for AUC0-inf to 1.1344 (90% CI, 1.0711–1.2014) for Cmax; results in the fasted group were similar. The secondary pooling set, which added a study in Asians, confirmed these findings. ImplicationsBioequivalence was determined between sustained-release formulations of GlucophageⓇ from Europe and the United States under fasted and fed conditions in healthy men and women, including different ethnicities. The efficacy and safety of GlucophageⓇ XR can be claimed along the evolution from oGXR US, via oGXR EU to rGXR EU, and in several ethnicities and production sites.