Bioequivalence of Empagliflozin and Metformin Given as a Fixed Dose Combination Compared to Single Tablets

Bioequivalence of Empagliflozin/Metformin (500 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 fixed dose combination (FDC) tablets (containing medium dose empagliflozin/500 mg metformin [Test 1] and low dose empagliflozin/500 mg metformin [Test 2]) and of the single tablets (medium dose empagliflozin tablets + Glucophage® 500 mg tablet [Reference 1] and low dose empagliflozin tablet + Glucophage® 500 mg tablet [Reference 2]) when administered together after a high fat, high caloric meal.

The assessment of safety and tolerability will be an additional objective of this trial.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: empagliflozin and metformin; Drug: empagliflozin; Drug: metformin (Glucophage®)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany
    • 1276.6.1 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
2. Subjects must be able to understand and comply with study requirements
3. Age 18 to 50 years
4. Body mass index (BMI) 18.5 to 29.9 kg/m2

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
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FDC empagliflozin dose 1 and metformin; fix dose combination tablet after intake of a high fat, high caloric meal	Drug: empagliflozin and metformin; FDC tablet empagliflozin and metformin
ACTIVE_COMPARATOR: empagliflozin dose 1 + metformin tablets; single tablets after intake of a high fat, high caloric meal	Drug: empagliflozin; single tablet empagliflozin; Drug: metformin (Glucophage®); single tablet metformin
EXPERIMENTAL: FDC empagliflozin dose 2 and metformin; fix dose combination tablet after intake of a high fat, high caloric meal	Drug: empagliflozin and metformin; FDC tablet empagliflozin and metformin
ACTIVE_COMPARATOR: empagliflozin dose 2 + metformin tablets; single tablets after intake of a high fat, high caloric meal	Drug: empagliflozin; single tablet empagliflozin; Drug: metformin (Glucophage®); single tablet metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-∞ for Empagliflozin	AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Empagliflozin	1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake
AUC0-∞ for Metformin	AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Metformin	1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake
Cmax for Empagliflozin	Cmax (maximum measured concentration of the analyte in plasma) for Empagliflozin	1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake
Cmax for Metformin	Cmax (maximum measured concentration of the analyte in plasma) for Metformin	1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-tz for Empagliflozin	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) for Empagliflozin	1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake
AUC0-tz for Metformin	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) for Metformin	1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: April 29, 2013
• First Submitted That Met QC Criteria: April 29, 2013
• First Posted (ESTIMATE): May 1, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): July 27, 2015
• Last Update Submitted That Met QC Criteria: June 26, 2015
• Last Verified: June 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: 1276.6; 2012-000082-20 (EUDRACT_NUMBER: EudraCT)