Bioequivalence Study to Compare Empagliflozin + Linagliptin 25 mg/5 mg Film-coated Tablets Versus Glyxambi 25 mg/ 5 mg Film-coated Tablets

An Open Label, Balanced, Randomized, Single Dose, Two Treatment, Two Sequence, Two Period, Two Way Crossover Oral Bioequivalence Study in Healthy, Adult, Human Subjects Under Fasting Condition

An open label, balanced, randomized, single dose, two treatment, two sequence, two period, two way crossover oral bioequivalence study in healthy, adult, human subjects under fasting condition.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Drug: Empagliflozin + Linagliptin film-coated tablets; Drug: Glyxambi film-coated tablets

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380 051
      • Veeda Clinical Research Ltd.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects aged between 18 to 45 years (both inclusive).
• Subjects' weight within normal range according to normal values for Body Mass Index (between 18.5 to 30.0 kg/m2) (both inclusive) with minimum of 45 kg weight.
• Subjects with normal health as determined by personal medical history, clinical examination and laboratory examinations within the clinically acceptable range.
• Subject with Creatinine Clearance ≥80 ml/min.
• Subjects having clinically acceptable 12-lead electrocardiogram (ECG).
• Subjects having clinically acceptable chest X-Ray (PA view), if taken.
• Subjects having negative urine screen for drugs of abuse (including amphetamines, barbiturates, benzodiazepines, marijuana, cocaine, and morphine).
• Subjects having negative urine alcohol test / breath alcohol test.
• Non-smoker
• Subjects willing to adhere to the protocol requirements and to provide written informed consent.

• For male Subjects:

  • Subjects willing to follow approved birth control methods (a double barrier method) for the duration of the study as judged by the investigator(s), such as (a double barrier method) condom with spermicide, Condom with diaphragm, or abstinence. Subjects willing to refrain from donating sperm during the study period.

• For Female Subjects:

  • Female of child bearing potential practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as intrauterine device (IUD), abstinence, bilateral tubal ligation or double barrier contraception, i.e., condom + diaphragm, condom + spermicidal or foam
  • Postmenopausal for at least 1 year, or if less than 1 year, then following acceptable contraceptive measures as mentioned above
• Subjects having negative urine pregnancy test at screening and negative serum β-hCG pregnancy test on admission day of period 01 (only for female subjects).

Exclusion Criteria:

• Hypersensitivity to Empagliflozin & Linagliptin or related class of drugs or any of its excipients or heparin.
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, urogenital or psychiatric disease or disorder.
• Any treatment which could bring about induction or inhibition of hepatic microsomal enzyme system within 30 days prior to admission in period 01.
• History or presence of alcoholism or drug abuse.
• History of any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis) History or presence of asthma, urticaria or other significant allergic reactions.
• History or presence of significant gastric and/or duodenal ulceration.
• History or presence of significant thyroid disease, adrenal dysfunction, organic intracranial lesion such as pituitary tumor.
• History or presence of cancer or basal or squamous cell carcinoma.
• Difficulty with donating blood.
• Difficulty in swallowing solids dosage form like tablets or capsules.
• Use of any prescribed medication or OTC medication including vaccines, vitamins and herbal remedies during last 30 days prior to admission in period 01.
• Major illness within past 3 months.
• Volunteer who have donated blood (1 unit) or participation in a drug research study within past 90 days prior to the first dose of the study drug.
• Consumption of xanthine-containing products, tobacco containing products or alcohol or any alcohol containing products within 48.00 hours prior to admission in period 01.
• Consumption of grapefruit or grapefruit juice containing products within 72.00 hours prior to admission of period 01.
• Positive screening test for any one or more: HIV, Hepatitis B and Hepatitis C.
• History or presence of significant easy bruising or bleeding.
• History or presence of significant recent trauma.
• Subjects who have been on an abnormal diet (for whatever reason) during the four weeks preceding the study.
• History of acute conditions with the potential to alter renal function.
• Female subjects who are currently breast feeding.

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 + Linagliptin film-coated tablets; Empagliflozin + Linagliptin 25 mg/5 mg film-coated tablets	Drug: Empagliflozin + Linagliptin film-coated tablets; 1 tablet of Empagliflozin + Linagliptin 25 mg/5 mg film-coated tablets; Drug: Glyxambi film-coated tablets; 1 tablet of Glyxambi 25 mg/ 5 mg film-coated tablets
Active Comparator: Glyxambi film-coated tablets; Glyxambi 25 mg/ 5 mg film-coated tablets	Drug: Empagliflozin + Linagliptin film-coated tablets; 1 tablet of Empagliflozin + Linagliptin 25 mg/5 mg film-coated tablets; Drug: Glyxambi film-coated tablets; 1 tablet of Glyxambi 25 mg/ 5 mg film-coated tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For Empagliflozin; Peak Plasma Concentration (Cmax)	The 90% confidence intervals for the difference between least square means of test (T) and reference (R) formulations will be calculated using mean square error, obtained in ANOVA, for ln-transformed pharmacokinetic parameters Cmax and AUC0-t for Empagliflozin & Cmax and AUC0-72 for Linagliptin.	72 hours
For Empagliflozin; The area under the plasma concentration versus time curve, from time 0 to the last measurable concentration, calculated using linear trapezoidal method (AUC0-t)	The 90% confidence intervals for the difference between least square means of test (T) and reference (R) formulations will be calculated using mean square error, obtained in ANOVA, for ln-transformed pharmacokinetic parameters Cmax and AUC0-t for Empagliflozin & Cmax and AUC0-72 for Linagliptin	72 hours
For Linagliptin; Peak Plasma Concentration (Cmax)	The 90% confidence intervals for the difference between least square means of test (T) and reference (R) formulations will be calculated using mean square error, obtained in ANOVA, for ln-transformed pharmacokinetic parameters Cmax and AUC0-t for Empagliflozin & Cmax and AUC0-72 for Linagliptin	72 hours
For Linagliptin; Area Under the Curve from time zero to time of last measurable concentration (AUC0-72)	The 90% confidence intervals for the difference between least square means of test (T) and reference (R) formulations will be calculated using mean square error, obtained in ANOVA, for ln-transformed pharmacokinetic parameters Cmax and AUC0-t for Empagliflozin & Cmax and AUC0-72 for Linagliptin	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For Empagliflozin; Area Under the Curve from time zero to time infinite (AUC0-∞)	Descriptive Statistic	72 hours
For Empagliflozin; Time to reach peak plasma concentration (Tmax)	Descriptive Statistic	72 hours
For Linagliptin; Time to reach peak plasma concentration (Tmax)	Descriptive Statistic	72 hours

Collaborators and Investigators

• Sponsor: Humanis Saglık Anonim Sirketi

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2024
• Primary Completion (Actual): March 7, 2025
• Study Completion (Actual): April 8, 2025

Study Registration Dates

• First Submitted: April 10, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 17, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Enzyme Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin; Empagliflozin
• Other Study ID Numbers: 24-VIN-0555

Drug and device information, study documents

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