Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Metformin Extended Release Compared With Mono Compound Tablets in Healthy Male and Female

Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Metformin Extended Release (10 mg/1000 mg) Compared With the Free Combination of Empagliflozin and Metformin Extended Release Tablets in Healthy Subjects Following a High-fat, High-caloric Meal (an Open-label, Randomised, Single Dose, Crossover Trial)

The purpose of this trial is to investigate bioequivalence of a newly developed fixed dose combination (FDC) tablet containing empagliflozin and metformin extended release compared to the free combination of empagliflozin and metformin extended release under fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: empagliflozin/metformin; Drug: metformin; Drug: empagliflozin

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Ingelheim, Germany
    • Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Healthy male and female subjects
• age of 18 to 55 years
• body mass index (BMI) of 18.5 to 29.9 kg/m2
• additional inclusion criteria may apply

Exclusion criteria:

• Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged as clinically relevant by the investigator
• Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg or diastolic blood pressure outside the range of 50 to 90 mmHg or pulse rate outside the range of 45 to 90 bpm
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease judged as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication
• Diseases of the central nervous system (including but not limited to any kind of seizures and stroke), and other relevant neurological disorders or psychiatric disorders
• additional exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fixed dose combination; Single dose empagliflozin/metformin	Drug: empagliflozin/metformin; Single dose empagliflozin/metformin given as fixed-dose combination tablet
ACTIVE_COMPARATOR: Single tablets combination; single doses empagliflozin and metformin	Drug: metformin; single dose of metformin given as tablets; Drug: empagliflozin; single dose of empagliflozin given as tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-tz of Empagliflozin in Plasma	Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration
AUC0-tz of Metformin in Plasma	Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration
Cmax of Empagliflozin in Plasma	Maximum measured concentration of the empagliflozin in plasma	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration
Cmax of Metformin in Plasma	Maximum measured concentration of the metformin in plasma	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-infinity of Empagliflozin in Plasma	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration
AUC0-infinity of Metformin in Plasma	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.	-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Eli Lilly and Company

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: October 16, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (ESTIMATE): October 17, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 9, 2017
• Last Update Submitted That Met QC Criteria: January 19, 2017
• Last Verified: January 1, 2017

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: 1276.28; 2014-002360-32 (EUDRACT_NUMBER: EudraCT)