Pharmacokinetics and Bioequivalence Study of Empagliflozin+Metformin Hydrochloride 5 mg/850 mg Film-coated Tablets (Gedeon Richter Plc., Hungary) Versus Synjardy® 5 mg/850 mg Film-coated Tablets (Boehringer Ingelheim International GmbH, Germany)

NCT06766500 | Completed Phase 1

• 1 other identifier: EAEU-GCO-MET/EMP-01-2023
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Empagliflozin and metformin hydrochloride are two separate drugs. The combination of these two drugs in one tablet are used for the treatment of type 2 diabetes, along with diet and exercise, and can be used with other drugs, if required. It is approved in Russia and also various other countries. In Russia, the brand name is Synjardy®. The purpose of this research study is to measure the amount of the two drugs in the blood after taking two different formulations of the combination tablet. One formulation, also called Synjardy®, is an approved product in Russia marketed by Boehringer Ingelheim International GmbH, Germany. The other formulation is an investigational product that is not approved. The data from this study will be used to compare the two products. Subjects participating in this study will take 5 mg empagliflozin and 850 mg metformin hydrochloride (1 combination film-coated tablet) of one formulation in each period. The maximum recommended daily dose is 25 mg of empagliflozin and 2,000 mg of metformin hydrochloride which is based on the subject's current regimen \[prescribed course of medical treatment\], effectiveness, and tolerability.

Conditions

Diabetes Mellitus Type 2

Keywords

Diabetes Mellitus Type 2; Diabetes; Empagliflozin; Metformin

Outcome Measures

Primary Outcomes (2)

• Bioequivalence of Empagliflozin + Metformin hydrochloride film-coated tablets and Synjardy® film-coated tablets via measuring the AUC from time 0 to last collection time t (AUC0-t)

  The primary purpose of the study is to assess the bioequivalence of Empagliflozin + Metformin hydrochloride 5 mg/850 mg film-coated tablets (Gedeon Richter Plc., Hungary) and Synjardy® 5 mg/850 mg film-coated tablets (Boehringer Ingelheim International GmbH, Germany) in healthy, adult volunteers under fed conditions. The measurement will be based on two-sided 90% CI for the test to reference ratio of the population means is within 80.00% to 125.00% for each of the Ln-transformed data of AUC.

  From enrollment to the end of treatment at about 7 weeks

• Bioequivalence of Empagliflozin + Metformin hydrochloride film-coated tablets and Synjardy® film-coated tablets via measuring the maximum concentration in plasma (Cmax)

  The primary purpose of the study is to assess the bioequivalence of Empagliflozin + Metformin hydrochloride 5 mg/850 mg film-coated tablets (Gedeon Richter Plc., Hungary) and Synjardy® 5 mg/850 mg film-coated tablets (Boehringer Ingelheim International GmbH, Germany) in healthy, adult volunteers under fed conditions. The measurement will be based on two-sided 90% CI for the test to reference ratio of the population means is within 80.00% to 125.00% for each of the Ln-transformed data of Cmax.

  From enrollment to the end of treatment at about 7 weeks

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  From enrollment to the end of treatment at about 7 weeks

Study Arms (2)

Empagliflozin + Metformin hydrochloride combination film-coated tablets

EXPERIMENTAL

Combination tablet of Empagliflozin + Metformin hydrochloride 5 mg/850 mg of Gedeon Richter Plc., Hungary

Drug: Empagliflozin + Metformin hydrochloride 5 mg/850 mg combination film-coated tablets

Synjardy® film-coated tablets

ACTIVE COMPARATOR

Synjardy® 5 mg/850 mg of Boehringer Ingelheim International GmbH, Germany

Drug: Synjardy® 5 mg/850 mg film-coated tablets

Interventions

Empagliflozin + Metformin hydrochloride 5 mg/850 mg combination film-coated tablets DRUG

1 tablet of Empagliflozin + Metformin hydrochloride 5 mg/850 mg combination film-coated tablet

Empagliflozin + Metformin hydrochloride combination film-coated tablets

Synjardy® 5 mg/850 mg film-coated tablets DRUG

1 tablet of Empagliflozin+Metformin 5 mg/850 mg filmcoated tablets

Synjardy® film-coated tablets

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Presence of the written informed consent of the volunteer to participate in the study in accordance with the current legislation, volunteer's agreement to observe all study restrictions and consent to come back to the center for providing of all study procedures.
• Verified as "healthy" by the Investigator based on the results of the standard clinical and laboratory tests and instrumental investigations, results of physical examination and medical history data;
• Male and female volunteers of Caucasian race, aged 18 to 45 years (inclusive) at screening.
• Female volunteers can be with childbearing or non-childbearing potential. Female volunteers of non-childbearing potential are defined as: females with documented menopause (defined as the absence of menstruation for at least 12 consecutive months without an alternative medical cause with follicle-stimulating hormone (FSH) level at screening ≥25 mIU/mL) or females with documented surgical sterilization (hysterectomy, bilateral ovary- or tubectomy, uterine tubes ligation);
• Body mass index (BMI) (by Quetelet) between 18.5 and 30 kg/m2 (inclusive). Body weight must be more than 45 kg and less than 100 kg;
• A volunteer must agree the following requirements:
• Female volunteers of childbearing potential must confirm the absence of unprotected sexual intercourse with unsterilized partner within 30 days before screening;
• Female volunteers must agree to sexual abstinence or to use consistently and correctly one of the adequate contraceptive methods listed below during their participation in this study and for 30 days after the last dose of the IMP;
• Male volunteers must agree to sexual abstinence or together with their female partners of childbearing potential must use consistently and correctly one of the adequate contraceptive methods listed below during their participation in this study and for 30 days after the last dose of the IMP;
• Male volunteers must agree to refrain from donating sperm during their participation in this study and for 30 days after the last dose of the IMP;
• Note: Adequate contraceptive methods include:
• Non-hormonal intrauterine device (IUD);
• Barrier method in combination with spermicidal drug or diaphragm (diaphragm with spermicide, cervical cap with spermicide, condom with spermicide).
• A volunteer has suitable veins for cannulation.

You may not qualify if:

• Known history or presence of clinically significant neurologic, hematologic, endocrine (including diabetes mellitus 1 and 2 type), oncologic, pulmonary, immunologic, genitourinary, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results;
• Known history or presence of clinically significant disease of the gastrointestinal tract, surgical interventions on gastrointestinal tract (except appendectomy);
• Burdened allergological anamnesis, including known history of anaphylactic reaction/anaphylactic shock, known history or presence of hypersensitivity or idiosyncratic reaction to empagliflozin or metformin or excipients of the test/reference product, or any other drug substances with similar activity;
• Acute or chronic infectious disease within 4 weeks before screening;
• History or presence of malignant disease;
• Presence of clinically significant hepatic or renal dysfunction as per Investigator's discretion;
• Estimated creatinine clearance of ≤60 mL/min based on the Cockcroft-Gault equation, or serum creatinine level higher than the upper limit of normal range of the local laboratory;
• Use of medication (prescribed, over-the-counter medications, and natural health products \[including herbal remedies, phytohormones, homeopathic and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports\]) within 14 days prior to screening and thereafter. It is allowed to use medical products without systemic absorption.
• Use of medications with potent effect on hemodynamics, and liver function (barbiturates, omeprazole, cimetidine, etc.) within 30 days before screening and thereafter;
• Donation of blood or plasma (450 ml and more) within 2 months before screening;
• Blood or plasma transfusion within 1 year before screening;
• Results of standard laboratory investigations outside the normal range of the local laboratory, which are considered clinically significant by the Investigator;
• ECG abnormalities, including clinically significant arrhythmia, or suspected arrhythmia as judged by the Investigator;
• Vital sign abnormalities at the screening (systolic blood pressure \[BP\] \< 100 or \> 130 mmHg, diastolic BP \< 60 or \> 90 mmHg, or heart rate \[HR\] \< 60 or \> 90 bpm);
• Positive test for hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or syphilis. It is allowed to use results of the HIV test, hepatitis viruses B and C tests and syphilis analysis, which were performed within 3 months before screening visit;

Sponsors & Collaborators

• Gedeon Richter Plc.: lead

Study Sites (1)

State Budgetary Institution of Healthcare of Yaroslavl region "Yaroslavl Regional Clinical Narcological Hospital"

Yaroslavl, 150054, Russia

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

empagliflozin; Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: January 9, 2025
• Study Start: January 20, 2025
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: April 16, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)