Bioavailability of a Fixed Dose Combination Tablet With Empagliflozin (BI 10773) and Metformin Compared With the Monocomponents and Effect of Food on Bioavailability

• ClinicalTrials.gov Identifier: NCT01211197
• Recruitment Status: Completed
• First Posted: September 29, 2010
• Results First Posted: August 21, 2015
• Last Update Posted: August 21, 2015
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

The objective of the current study is to determine the relative bioavailability of a BI 10773 / metformin fixed dose combination tablet compared to single tablets of BI 10773 and metformin when administered together and to assess the effect of food on the bioavailability the fixed dose combination tablet

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: C: BI 10773 / metformin tablet; Drug: B: BI 10773 tablet and metformin tablet; Drug: A: BI 10773 / metformin tablet	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Relative Bioavailability of a 12.5 mg BI 10773 / 1000 mg Metformin Fixed Dose Combination Tablet Compared With Its Monocomponents and Administered With and Without Food (an Open-label, Randomised, Single-dose, Three-way Crossover, Phase I Trial in Healthy Volunteers)
• Study Start Date: October 2010
• Actual Primary Completion Date: December 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: A; 3 treatments will be investigated in randomized order	Drug: A: BI 10773 / metformin tablet; BI 10773 / metformin fixed dose combination tablet in fasted state
Experimental: B; 3 treatments will be investigated in randomized order	Drug: B: BI 10773 tablet and metformin tablet; BI 10773 and metformin single tablets, administered together in fasted state
Experimental: C; 3 treatments will be investigated in randomized order	Drug: C: BI 10773 / metformin tablet; BI 10773 / metformin fixed dose combination tablet after a high fat, high caloric meal

Outcome Measures

Primary Outcome Measures :

1. Empa: Area Under the Curve 0 to Infinity (AUC0-∞) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity.

   Note the standard deviation is actually the coefficient of variation (CV).

2. Empa: Maximum Measured Concentration (Cmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Maximum measured concentration of empagliflozin (empa) in plasma.

   Note the standard deviation is actually the CV.

3. Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity.

   Note the standard deviation is actually the CV.

4. Metformin: Maximum Measured Concentration (Cmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Maximum measured concentration of metformin in plasma.

   Note the standard deviation is actually the CV.

Secondary Outcome Measures :

1. Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the time of the last quantifiable data point.

   Note the standard deviation is actually the CV.

2. Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable data point.

   Note the standard deviation is actually the CV.

3. Time to Maximum Measured Concentration (Tmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Time from dosing to the maximum concentration of the analyte in plasma.

   Note the standard deviation is actually the CV.

4. Terminal Elimination Rate Constant in Plasma (λz) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Terminal elimination rate constant in plasma.

   Note the standard deviation is actually the CV.

5. Terminal Half-life in Plasma (T1/2) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Terminal half-life of the analyte in plasma.

   Note the standard deviation is actually the CV.

6. Mean Residence Time in the Body After Oral Administration (MRTpo) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Mean residence time of the analyte in the body after oral administration.

   Note the standard deviation is actually the CV.

7. Apparent Clearance After Extravascular Administration (CL/F) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Apparent clearance of the analyte in the plasma after extravascular administration.

   Note the standard deviation is actually the CV.

8. Apparent Volume of Distribution During the Terminal Phase (Vz/F) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ]

   Apparent volume of distribution during the terminal phase (λz).

   Note the standard deviation is actually the CV.

9. Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator. [ Time Frame: Drug administration up to 7 days after last drug administration, up to 8 days ]
   Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria:

1. Healthy males and females according to the following criteria
2. Body Mass Index 18.5 to 29.9 kg/m2 (incl.)

Exclusion criteria:

1. Any finding of the medical examination (including Blood Pressure, Pulse Rate and electrocardiogram) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease

Contacts and Locations

Locations

Germany

1276.5.1 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: NCT01211197
• Other Study ID Numbers: 1276.5; 2010-018589-22 ( EudraCT Number: EudraCT )
• First Posted: September 29, 2010
• Results First Posted: August 21, 2015
• Last Update Posted: August 21, 2015
• Last Verified: July 2015

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Metformin; Empagliflozin; Hypoglycemic Agents; Physiological Effects of Drugs; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action