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

• ClinicalTrials.gov Identifier: NCT01844531
• Recruitment Status: Completed
• First Posted: May 1, 2013
• Results First Posted: July 27, 2015
• Last Update Posted: July 27, 2015
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: empagliflozin; Drug: metformin (Glucophage®); Drug: empagliflozin and metformin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: April 2013
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: November 2013

Arms and Interventions

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: metformin (Glucophage®); single tablet metformin; Drug: empagliflozin; single tablet empagliflozin

Outcome Measures

Primary Outcome Measures :

1. AUC0-∞ for Empagliflozin [ Time Frame: 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-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Empagliflozin
2. AUC0-∞ for Metformin [ Time Frame: 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-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Metformin
3. Cmax for Empagliflozin [ Time Frame: 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 (maximum measured concentration of the analyte in plasma) for Empagliflozin
4. Cmax for Metformin [ Time Frame: 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 (maximum measured concentration of the analyte in plasma) for Metformin

Secondary Outcome Measures :

1. AUC0-tz for Empagliflozin [ Time Frame: 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 (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
2. AUC0-tz for Metformin [ Time Frame: 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 (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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Germany

1276.6.1 Boehringer Ingelheim Investigational Site

Biberach, Germany

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Related Info 

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01844531
• Other Study ID Numbers: 1276.6; 2012-000082-20 ( EudraCT Number: EudraCT )
• First Posted: May 1, 2013
• Results First Posted: July 27, 2015
• Last Update Posted: July 27, 2015
• Last Verified: June 2015

Additional relevant MeSH terms:

Metformin; Empagliflozin; Hypoglycemic Agents; Physiological Effects of Drugs; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action