Bioavailability of Empagliflozin/Metformin Fixed Dose Combinations (FDCs) in Healthy Chinese Volunteers

Relative Bioavailability of Empagliflozin (12.5 or 5 mg)/Metformin (850 mg or 500 mg) Fixed Dose Combination Tablets Compared to Single Tablets Administered Together to Healthy Chinese Male and Female Volunteers in an Open-label, Randomised, Single-dose, Two-way Crossover Study

The aim of the trial is to assess the relative bioavailability of fixed dose combination tablets of Empagliflozin and metformin compared to the administration of single tablets (Empagliflozin and metformin ) in Chinese subjects. The availability of a fixed dose combination tablet is expected to significantly enhance patient's compliance with antidiabetic treatment, in particular with concern to the frequent polypharmacy in diabetic patients.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: 12.5 mg empagliflozin; Drug: 12.5 mg empagliflozin; Drug: 850 mg metformin; Drug: 850 mg metformin; Drug: 12.5 mg empagliflozin/850 mg metformin FDC; Drug: 5 mg empagliflozin/850 mg metformin FDC; Drug: 5 mg empagliflozin; Drug: 12.5 mg empagliflozin/500 mg metformin FDC; Drug: 500 mg metformin; Drug: 5 mg empagliflozin/500 mg metformin FDC

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • 1276.23.86002 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Healthy male and female subjects

Exclusion criteria:

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: 12.5 mg empagliflozin/850 mg metformin; 24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of 12.5 mg empagliflozin/850 mg metformin and single 10 mg empagliflozin, 2.5 mg empagliflozin, 850 mg metformin tablets single dose in randomized order	Drug: 12.5 mg empagliflozin; 10 mg empagliflozin tablet and 2.5 mg empagliflozin tablet; Drug: 12.5 mg empagliflozin; 10mg empagliflozin tablet and 2.5 mg empagliflozin tablet; Drug: 850 mg metformin; 850mg metformin tablet; Drug: 850 mg metformin; 850 mg metformin; Drug: 12.5 mg empagliflozin/850 mg metformin FDC; 12.5 mg empagliflozin/850 mg metformin FDC
Experimental: 5 mg empagliflozin/850 mg metformin; 24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of 5 mg empagliflozin/850 mg metformin and single Empagliflozin(5mg) and metformin (850mg) tablets single dose in randomized order	Drug: 850 mg metformin; 850mg metformin tablet; Drug: 850 mg metformin; 850 mg metformin; Drug: 5 mg empagliflozin/850 mg metformin FDC; 5 mg empagliflozin/850 mg metformin FDC; Drug: 5 mg empagliflozin; 5 mg empagliflozin
Experimental: 12.5 mg empagliflozin/500 mg metformin; 24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of 12.5 mg empagliflozin/500 mg metformin and single 10 mg empagliflozin, 2.5 mg empagliflozin, 500 mg metformin tablets single dose in randomized order	Drug: 12.5 mg empagliflozin; 10 mg empagliflozin tablet and 2.5 mg empagliflozin tablet; Drug: 12.5 mg empagliflozin; 10mg empagliflozin tablet and 2.5 mg empagliflozin tablet; Drug: 12.5 mg empagliflozin/500 mg metformin FDC; 12.5 mg empagliflozin/500 mg metformin FDC; Drug: 500 mg metformin; 500 mg metformin
Experimental: 5 mg empagliflozin/500 mg metformin; 24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of 5 mg empagliflozin/500 mg metformin and single Empagliflozin(5mg) and metformin (500mg) tablets single dose in randomized order	Drug: 5 mg empagliflozin; 5 mg empagliflozin; Drug: 500 mg metformin; 500 mg metformin; Drug: 5 mg empagliflozin/500 mg metformin FDC; 5 mg empagliflozin/500 mg metformin FDC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(0-∞) for Empagliflozin	Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity	1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
AUC(0-∞) for Metformin	Area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity	1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Cmax for Empagliflozin	Maximum measured concentration of the empagliflozin in plasma	1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Cmax for Metformin	Maximum measured concentration of the metformin in plasma	1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(0-tz) of Empagliflozin	Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 up to the last quantifiable data point	1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
AUC(0-tz) of Metformin	Area under the concentration-time curve of the metformin in plasma over the time interval from 0 up to the last quantifiable data point	1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h 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: May 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimate): April 3, 2014

Study Record Updates

• Last Update Posted (Estimate): September 24, 2015
• Last Update Submitted That Met QC Criteria: August 21, 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: 1276.23