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

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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:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: C: BI 10773 / metformin tablet
Drug: B: BI 10773 tablet and metformin tablet
Drug: A: BI 10773 / metformin tablet
Enrollment 16
Recruitment Details  
Pre-assignment Details An open label, randomised, three-way crossover study. A washout period of at least 7 days was respected between drug administrations.
Arm/Group Title FDC Fasted / Individual Tablets Fasted / FDC Fed FDC Fasted / FDC Fed / Individual Tablets Fasted Individual Tablets Fasted / FDC Fasted / FDC Fed Individual Tablets Fasted / FDC Fed / FDC Fasted FDC Fed / FDC Fasted / Individual Tablets Fasted FDC Fed / Individual Tablets Fasted / FDC Fasted
Hide Arm/Group Description

Patients received the three treatments in the following order:

  • FDC tablet, containing 12.5mg empagliflozin (BI 10773) and 1000mg metformin, under fasted conditions
  • 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions

Patients received the three treatments in the following order:

  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
  • 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions

Patients received the three treatments in the following order:

  • 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions

Patients received the three treatments in the following order:

  • 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions

Patients received the three treatments in the following order:

  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
  • 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions

Patients received the three treatments in the following order:

  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
  • 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
  • FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
Period Title: Treatment Period 1 (1 Day)
Started 3 3 3 3 2 2
Completed 3 3 3 3 2 2
Not Completed 0 0 0 0 0 0
Period Title: Washout Period 1 (7 Days)
Started 3 3 3 3 2 2
Completed 3 3 2 3 2 2
Not Completed 0 0 1 0 0 0
Reason Not Completed
Withdrawal by Subject             0             0             1             0             0             0
Period Title: Treatment Period 2 (1 Day)
Started 3 3 2 3 2 2
Completed 3 3 2 3 2 2
Not Completed 0 0 0 0 0 0
Period Title: Washout Period 2 (7 Days)
Started 3 3 2 3 2 2
Completed 2 3 2 3 2 2
Not Completed 1 0 0 0 0 0
Reason Not Completed
Adverse Event             1             0             0             0             0             0
Period Title: Treatment Period 3 (1 Day)
Started 2 3 2 3 2 2
Completed 2 3 2 3 2 2
Not Completed 0 0 0 0 0 0
Arm/Group Title Study Overall
Hide Arm/Group Description

An open label, randomised, three-way crossover study. The three treatments administered were

  • Fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
  • 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
  • Fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions

A washout period of at least 7 days was respected between drug administrations.

Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
35.8  (7.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
9
  56.3%
Male
7
  43.8%
1.Primary Outcome
Title Empa: Area Under the Curve 0 to Infinity (AUC0-∞)
Hide Description

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).

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: nmol*h/L
2920  (16.2) 2860  (18.5) 2710  (15.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FDC Fasted, Individual Tablets Fasted
Comments Ratio calculated as FDC fasted divided by individual tablets fasted.
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 100.59
Confidence Interval (2-Sided) 90%
95.75 to 105.67
Parameter Dispersion
Type: Standard Deviation
Value: 7.6
Estimation Comments Standard deviation is actually the intra-individual geometric coefficient of variation (gCV).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FDC Fasted, FDC Fed
Comments Ratio calculated as FDC fed divided by FDC fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 94.94
Confidence Interval (2-Sided) 90%
89.85 to 100.33
Parameter Dispersion
Type: Standard Deviation
Value: 8.0
Estimation Comments Standard deviation is actually the intra-individual gCV.
2.Primary Outcome
Title Empa: Maximum Measured Concentration (Cmax)
Hide Description

Maximum measured concentration of empagliflozin (empa) in plasma.

Note the standard deviation is actually the CV.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: nmol/L
404  (17.4) 405  (15.8) 259  (20.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FDC Fasted, Individual Tablets Fasted
Comments Ratio calculated as FDC fasted divided by individual tablets fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 99.31
Confidence Interval (2-Sided) 90%
91.76 to 107.49
Parameter Dispersion
Type: Standard Deviation
Value: 12.2
Estimation Comments Standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FDC Fasted, FDC Fed
Comments Ratio calculated as FDC fed divided by FDC fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 64.30
Confidence Interval (2-Sided) 90%
55.97 to 73.87
Parameter Dispersion
Type: Standard Deviation
Value: 20.6
Estimation Comments Standard deviation is actually the intra-individual gCV.
3.Primary Outcome
Title Metformin: Area Under the Curve 0 to Infinity (AUC0-∞)
Hide Description

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.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
10300  (16.9) 10100  (21.2) 10200  (15.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FDC Fasted, Individual Tablets Fasted
Comments Ratio calculated as FDC fasted divided by individual tablets fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 102.15
Confidence Interval (2-Sided) 90%
93.87 to 111.15
Parameter Dispersion
Type: Standard Deviation
Value: 13.0
Estimation Comments Standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FDC Fasted, FDC Fed
Comments Ratio calculated as FDC fed divided by FDC fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 100.67
Confidence Interval (2-Sided) 90%
91.70 to 110.51
Parameter Dispersion
Type: Standard Deviation
Value: 13.7
Estimation Comments Standard deviation is actually the intra-individual gCV.
4.Primary Outcome
Title Metformin: Maximum Measured Concentration (Cmax)
Hide Description

Maximum measured concentration of metformin in plasma.

Note the standard deviation is actually the CV.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
1550  (19.1) 1530  (23.4) 1180  (25.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FDC Fasted, Individual Tablets Fasted
Comments Ratio calculated as FDC fasted divided by individual tablets fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 103.49
Confidence Interval (2-Sided) 90%
95.30 to 112.39
Parameter Dispersion
Type: Standard Deviation
Value: 12.7
Estimation Comments Standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FDC Fasted, FDC Fed
Comments Ratio calculated as FDC fed divided by FDC fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 75.13
Confidence Interval (2-Sided) 90%
63.68 to 88.64
Parameter Dispersion
Type: Standard Deviation
Value: 24.5
Estimation Comments Standard deviation is actually the intra-individual gCV.
5.Secondary Outcome
Title Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
Hide Description

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.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: nmol*h/L
2860  (16.3) 2800  (18.6) 2640  (15.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FDC Fasted, Individual Tablets Fasted
Comments Ratio calculated as FDC fasted divided by individual tablets fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 100.94
Confidence Interval (2-Sided) 90%
96.03 to 106.11
Parameter Dispersion
Type: Standard Deviation
Value: 7.7
Estimation Comments Standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FDC Fasted, FDC Fed
Comments Ratio calculated as FDC fed divided by FDC fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 94.39
Confidence Interval (2-Sided) 90%
89.22 to 99.87
Parameter Dispersion
Type: Standard Deviation
Value: 8.2
Estimation Comments Standard deviation is actually the intra-individual gCV.
6.Secondary Outcome
Title Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
Hide Description

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.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
9900  (17.9) 9720  (22.3) 9550  (19.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FDC Fasted, Individual Tablets Fasted
Comments Ratio calculated as FDC fasted divided by individual tablets fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 103.13
Confidence Interval (2-Sided) 90%
95.59 to 111.25
Parameter Dispersion
Type: Standard Deviation
Value: 11.7
Estimation Comments Standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FDC Fasted, FDC Fed
Comments Ratio calculated as FDC fed divided by FDC fasted
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 96.96
Confidence Interval (2-Sided) 90%
87.23 to 107.78
Parameter Dispersion
Type: Standard Deviation
Value: 15.5
Estimation Comments Standard deviation is actually the intra-individual gCV.
7.Secondary Outcome
Title Time to Maximum Measured Concentration (Tmax)
Hide Description

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

Note the standard deviation is actually the CV.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Median (Full Range)
Unit of Measure: hours
Tmax of empagliflozin
1.50
(0.67 to 2.50)
1.75
(1.00 to 2.50)
3.00
(1.00 to 8.00)
Tmax of metformin
2.50
(2.00 to 4.00)
2.50
(1.50 to 4.00)
3.00
(1.50 to 8.00)
8.Secondary Outcome
Title Terminal Elimination Rate Constant in Plasma (λz)
Hide Description

Terminal elimination rate constant in plasma.

Note the standard deviation is actually the CV.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: 1/h
λz of empagliflozin 0.0559  (43.9) 0.0601  (53.2) 0.0498  (46.6)
λz of metformin 0.0822  (73.3) 0.0756  (82.7) 0.0590  (108)
9.Secondary Outcome
Title Terminal Half-life in Plasma (T1/2)
Hide Description

Terminal half-life of the analyte in plasma.

Note the standard deviation is actually the CV.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: hours
T1/2 of empagliflozin 15.1  (46.6) 16.0  (61.3) 16.7  (43.0)
T1/2 of metformin 16.6  (94.6) 17.8  (76.9) 30.5  (89.0)
10.Secondary Outcome
Title Mean Residence Time in the Body After Oral Administration (MRTpo)
Hide Description

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

Note the standard deviation is actually the CV.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: hours
MRTpo of empagliflozin 10.5  (17.6) 10.9  (25.1) 13.9  (23.0)
MRTpo of metformin 9.53  (52.0) 10.2  (52.1) 19.4  (101)
11.Secondary Outcome
Title Apparent Clearance After Extravascular Administration (CL/F)
Hide Description

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

Note the standard deviation is actually the CV.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: mL/min
CL/F of empagliflozin 162  (15.0) 166  (17.1) 174  (13.3)
CL/F of metformin 1670  (20.2) 1730  (25.4) 1670  (18.8)
12.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Hide Description

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

Note the standard deviation is actually the CV.

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Mean (Standard Deviation)
Unit of Measure: Litres
Vz/F of empagliflozin 210  (45.3) 222  (58.0) 250  (44.3)
Vz/F of metformin 2410  (99.5) 2650  (86.0) 4670  (112)
13.Secondary Outcome
Title Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator.
Hide Description 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.
Time Frame Drug administration up to 7 days after last drug administration, up to 8 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set (TS) includes all subjects who took at least 1 dose of investigational medication and was used for safety analysis.
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description:
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
Overall Number of Participants Analyzed 15 16 14
Measure Type: Number
Unit of Measure: participants
0 0 0
Time Frame Drug administration up to 7 days after last drug administration, up to 8 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title FDC Fasted Individual Tablets Fasted FDC Fed
Hide Arm/Group Description A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions. 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions. A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
All-Cause Mortality
FDC Fasted Individual Tablets Fasted FDC Fed
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
FDC Fasted Individual Tablets Fasted FDC Fed
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/16 (0.00%)   0/14 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
FDC Fasted Individual Tablets Fasted FDC Fed
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/15 (13.33%)   6/16 (37.50%)   8/14 (57.14%) 
Gastrointestinal disorders       
Diarrhoea  1  2/15 (13.33%)  3/16 (18.75%)  3/14 (21.43%) 
Infections and infestations       
Nasopharyngitis  1  0/15 (0.00%)  0/16 (0.00%)  1/14 (7.14%) 
Rhinitis  1  0/15 (0.00%)  0/16 (0.00%)  1/14 (7.14%) 
Urinary tract infection  1  0/15 (0.00%)  1/16 (6.25%)  0/14 (0.00%) 
Injury, poisoning and procedural complications       
Ligament sprain  1  0/15 (0.00%)  0/16 (0.00%)  1/14 (7.14%) 
Wound  1  0/15 (0.00%)  1/16 (6.25%)  0/14 (0.00%) 
Nervous system disorders       
Dizziness  1  0/15 (0.00%)  1/16 (6.25%)  1/14 (7.14%) 
Headache  1  1/15 (6.67%)  1/16 (6.25%)  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain  1  0/15 (0.00%)  1/16 (6.25%)  0/14 (0.00%) 
Skin and subcutaneous tissue disorders       
Dermatitis contact  1  0/15 (0.00%)  0/16 (0.00%)  1/14 (7.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 13.1
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01211197     History of Changes
Other Study ID Numbers: 1276.5
2010-018589-22 ( EudraCT Number: EudraCT )
First Submitted: September 28, 2010
First Posted: September 29, 2010
Results First Submitted: June 26, 2015
Results First Posted: August 21, 2015
Last Update Posted: August 21, 2015