Bioequivalence Study to Compare Empagliflozin/ Metformin HCl 12.5mg/1000mg Film-coated Tablets

Randomized, Two-way, Two-period, Single Oral Dose, Open-label, Crossover, Bioequivalence Study to Compare Empagliflozin/ Metformin HCl 12.5mg/1000mg Film-coated Tablets (12.5mg Empagliflozin / 1000mg Metformin HCl) Versus Synjardy® 12.5mg/1000mg Film-coated Tablets (12.5mg Empagliflozin/ 1000mg Metformin HCl) in Healthy Subjects Under Fed Conditions

Randomized, two-way, two-period, single oral dose, open-label, crossover, bioequivalence study to compare Empagliflozin/ Metformin HCl 12.5mg/1000mg film-coated tablets (12.5mg Empagliflozin / 1000mg Metformin HCl) versus Synjardy® 12.5mg/1000mg film-coated tablets (12.5mg Empagliflozin/ 1000mg Metformin HCl) in healthy subjects under fed conditions.

Study Overview

• Status: Completed
• Conditions: Type2diabetes
• Intervention / Treatment: Drug: Emapgliflozin/Metformin 12.5mg/1000mg Film-coated tablets; Drug: Synjardy® 12.5mg/1000mg film-coated tablets

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Jordan
  • Amman, Jordan
    • ACDIMA Biocenter

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

A. The subject is Caucasian & aged between eighteen & fifty years (18 - 50), both inclusive.

B. The subject is within the limits for his height & weight as defined by the body mass index range (18.5 - 30.0 kg/m2).

C. The subject is willing to undergo the necessary pre- & post- medical examinations set by this study.

D. The results of medical history, physical examination, vital signs & conducted medical laboratory tests are normal as determined by the clinical investigator.

E. The subject tested negative for Hepatitis B (HBsAg), Hepatitis C (HCVAb) and human immunodeficiency virus (HIVAb).

F. There is no evidence of psychiatric disorder, antagonistic personality, and poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements.

G. The subject is able to understand and willing to sign the informed consent form.

H. For female subjects: negative serum pregnancy test and the woman is using two reliable contraception methods and not lactating.

I. The subject has normal cardiovascular system & normal ECG recording with normal QT interval corrected for heart rate according to Bazett's formula.

J. The subject's kidney and liver (AST & ALT enzymes) function tests are within normal range. (Creatinine is accepted if below the reference range after being evaluated by the CI as clinically not significant).

K. The subject HbA1c test result is within normal range. (HbA1c is accepted if below the reference range after being evaluated by the CI as clinically not significant.) L. The subject's fasting blood glucose level is ≥ 70mg/dL before dosing.

Exclusion Criteria:

A. The subject is a heavy smoker (more than 10 cigarettes per day). B. The subject has suffered an acute illness one week before dosing. C. The subject has a history of or concurrent abuse of alcohol. D. The subject has a history of or concurrent abuse of illicit drugs. E. The subject has a history of hypersensitivity and/or contraindications to the study drug and any related compounds.

F. The subject has been hospitalized within three months before the study or during the study.

G. The subject is on special diet (for example subject is vegetarian). H. The subject has consumed caffeine or xanthine containing beverages or foodstuffs within two days before dosing and until 72 hours after dosing in either study period.

I. The subject has taken a prescription medication within two weeks or even an over the counter product (OTC) within one week before dosing in each study period and any time during the study, unless otherwise judged acceptable by the clinical investigator.

J. The subject has taken grapefruit/ orange containing beverages or foodstuffs within seven (7) days before first dosing and any time during the study.

K. The subject has been participating in any clinical study (e.g. pharmacokinetics, bioavailability and bioequivalence studies) within the last 80 days prior to the present study.

L. The subject has donated blood within 80 days before first dosing. M. The subject has a history or presence of cardiovascular, pulmonary, renal, hepatic, gastrointestinal, hematological, endocrinal, immunological, dermatological, neurological, musculoskeletal or psychiatric diseases.

N. The subject has consumed drugs that may affect pharmacological or pharmacokinetic properties of Metformin or Empagliflozin (for example: Probenecid, Rifampicin, Gemfibrozil, Glimepiride, Sitagliptin, Linagliptin, Warfarin, Verapamil, Ramipril, Torasemide, Hydrochlorothiazide, Lithium, Cimetidine, Dolutegravir, Ranolazine, Trimethoprime, Vandetanib, Isavuconazole, Glucocorticoids, Insulin and insulin secretagogues (Sulphonylureas)) two weeks before dosing, during the study and two weeks after dosing.

O. Female subjects planning to become pregnant. P. The subject has a presence of ketone in urine, presence of any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis), Diabetic pre-coma and/or disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic disease) such as: decompensated heart failure, respiratory failure, recent myocardial infarction and shock.

Note: Subjects, who were screened for another study and were not enrolled, might be recruited for this study provided they meet the acceptance criteria of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin/ Metformin HCl Film Coated Tablet; Empagliflozin/ Metformin HCl 12.5mg/1000 mg Film Coated Tablet (12.5mg Empagliflozin / 1000mg Metformin HCl)	Drug: Emapgliflozin/Metformin 12.5mg/1000mg Film-coated tablets; 1 tablet of Emapgliflozin/Metformin 12.5mg/1000mg Film-coated tablets
Active Comparator: Synjardy® film-coated tablets; Synjardy® 12.5mg/1000mg film-coated tablets (12.5mg Empagliflozin / 1000mg Metformin HCl)	Drug: Synjardy® 12.5mg/1000mg film-coated tablets; 1 tablet of Emapgliflozin/Metformin 12.5mg/1000mg Film-coated tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration obtained (Cmax)	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 Cmax	23 hours
AUC from time 0 to last collection time t (AUC0-t)	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 AUC0-t	23 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC from time 0 to infinity (AUC0-inf)	Description Statistics	23 hours
Time of the maximum measured plasma concentration (Tmax)	Description Statistics	23 hours

Collaborators and Investigators

• Sponsor: Humanis Saglık Anonim Sirketi

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2024
• Primary Completion (Actual): January 16, 2024
• Study Completion (Actual): March 5, 2024

Study Registration Dates

• First Submitted: June 4, 2024
• First Submitted That Met QC Criteria: June 7, 2024
• First Posted (Actual): June 10, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2024
• Last Update Submitted That Met QC Criteria: June 7, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 1255-2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No