Demonstration of Bioequivalence of Empagliflozin and Metformin Given in One Tablet Compared to the Intake of Single Tablets

Bioequivalence of Empagliflozin/Metformin (850 mg) Fixed Dose Combination Tablets Compared to Single Tablets Administered Together in Healthy Male and Female Volunteers Under Fed Conditions (an Open-label, Randomised, Single-dose, Four-way Crossover Study)

The primary objective of this trial is to establish bioequivalence of two FDC tablets and the single tablets when administered together after a high fat high caloric meal.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Empagliflozin + Metformin; Drug: Empagliflozin; Drug: Metformin; Drug: Metformin; Drug: Empagliflozin

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

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany
    • 1276.7.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Healthy male and female subjects

Exclusion criteria:

1. Any relevant deviation from healthy conditions

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test 1; fixed dose combination tablet	Drug: Empagliflozin + Metformin; fixed dose combination tablet (low)
Active Comparator: Reference 1; empagliflozin tablets and metformin tablet	Drug: Empagliflozin; empagliflozin tablets and metformin tablet; Drug: Metformin; empagliflozin tablets and metformin tablet; Drug: Metformin; empagliflozin tablet and metformin tablet; Drug: Empagliflozin; empagliflozin tablet and metformin tablet
Experimental: Test 2; fixed dose combination tablet	Drug: Empagliflozin + Metformin; fixed dose combination tablet (low)
Active Comparator: Reference 2; empagliflozin tablet and metformin tablet	Drug: Empagliflozin; empagliflozin tablets and metformin tablet; Drug: Metformin; empagliflozin tablets and metformin tablet; Drug: Metformin; empagliflozin tablet and metformin tablet; Drug: Empagliflozin; empagliflozin tablet and metformin tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Empa: Area Under the Curve 0 to Infinity (AUC0-∞)	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.	1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Metformin: Area Under the Curve 0 to Infinity (AUC0-∞)	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.	1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Empa: Maximum Measured Concentration (Cmax)	Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.	1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Metformin: Maximum Measured Concentration (Cmax)	Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.	1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.	1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.	1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: August 22, 2012
• First Submitted That Met QC Criteria: August 22, 2012
• First Posted (Estimate): August 27, 2012

Study Record Updates

• Last Update Posted (Estimate): August 31, 2015
• Last Update Submitted That Met QC Criteria: August 4, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Metformin; Empagliflozin
• Other Study ID Numbers: 1276.7; 2012-002277-65 (EudraCT Number: EudraCT)