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

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ClinicalTrials.gov Identifier: NCT02102932
Recruitment Status : Completed
First Posted : April 3, 2014
Results First Posted : September 24, 2015
Last Update Posted : September 24, 2015
Sponsor:
Collaborator:
Eli Lilly and Company
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 Healthy
Interventions Drug: 5 mg empagliflozin/850 mg metformin FDC
Drug: 12.5 mg empagliflozin
Drug: 850 mg metformin
Drug: 5 mg empagliflozin
Drug: 12.5 mg empagliflozin/850 mg metformin FDC
Drug: 12.5 mg empagliflozin/500 mg metformin FDC
Drug: 5 mg empagliflozin/500 mg metformin FDC
Drug: 500 mg metformin
Enrollment 96
Recruitment Details The study was performed as an open-label, randomised, single-dose, two-way crossover trial consisting of four trial parts. In each trial part the aim was to investigate the relative bioavailability of the Test treatment (T) and to compare it with the Reference treatment (R).
Pre-assignment Details  
Arm/Group Title T1R1 R1T1 T2R2 R2T2 T3R3 R3T3 T4R4 R4T4
Hide Arm/Group Description

Study Part 1:

T1: Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin R1: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg; A washout period of at least 7 days was to be maintained between T1 and R1.

Study Part 1:

R1: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg T1: Oral administration of a single FDC tablet 12.5 mg empagliflozin/850 mg metformin; A washout period of at least 7 days was to be maintained between R1 and T1.

Study Part 2:

T2: Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin R2: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg; A washout period of at least 7 days was to be maintained between T2 and R2.

Study part 2:

R2: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg; T2: Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin; A washout period of at least 7 days was to be maintained between R2 and T2.

Study Part 3:

T3: Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin R3: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg; A washout period of at least 7 days was to be maintained between T3 and R3.

Study Part 3:

R3: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg T3: Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin; A washout period of at least 7 days was to be maintained between R3 and T3

Study Part 4:

T4: Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin R4: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg; A washout period of at least 7 days was to be maintained between T4 and R4.

Study Part 4:

R4: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg; T4: Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin; A washout period of at least 7 days was to be maintained between R4 and T4

Period Title: Overall Study
Started 12 12 12 12 12 12 12 12
Completed 12 12 12 12 12 12 12 12
Not Completed 0 0 0 0 0 0 0 0
Arm/Group Title T1R1 R1T1 T2R2 R2T2 T3R3 R3T3 T4R4 R4T4 Total
Hide Arm/Group Description

Study Part 1:

T1: Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin R1: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg; A washout period of at least 7 days was to be maintained between T1 and R1.

Study Part 1:

R1: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg T1: Oral administration of a single FDC tablet 12.5 mg empagliflozin/850 mg metformin; A washout period of at least 7 days was to be maintained between R1 and T1.

Study Part 2:

T2: Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin R2: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg; A washout period of at least 7 days was to be maintained between T2 and R2.

Study part 2:

R2: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg; T2: Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin; A washout period of at least 7 days was to be maintained between R2 and T2.

Study Part 3:

T3: Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin R3: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg; A washout period of at least 7 days was to be maintained between T3 and R3.

Study Part 3:

R3: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg T3: Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin; A washout period of at least 7 days was to be maintained between R3 and T3

Study Part 4:

T4: Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin R4: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg; A washout period of at least 7 days was to be maintained between T4 and R4.

Study Part 4:

R4: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg; T4: Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin; A washout period of at least 7 days was to be maintained between R4 and T4

Total of all reporting groups
Overall Number of Baseline Participants 12 12 12 12 12 12 12 12 96
Hide Baseline Analysis Population Description
Treated set (TS): The TS included all subjects who were dispensed study medication and were documented to have received at least 1 dose of trial medication
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 12 participants 12 participants 12 participants 12 participants 12 participants 12 participants 96 participants
26.9  (4.8) 27.0  (5.3) 26.8  (5.3) 24.3  (3.4) 24.8  (4.3) 24.4  (3.9) 24.6  (3.7) 25.6  (4.8) 25.5  (4.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 12 participants 12 participants 12 participants 12 participants 12 participants 96 participants
Female
7
  58.3%
5
  41.7%
7
  58.3%
5
  41.7%
5
  41.7%
7
  58.3%
5
  41.7%
7
  58.3%
48
  50.0%
Male
5
  41.7%
7
  58.3%
5
  41.7%
7
  58.3%
7
  58.3%
5
  41.7%
7
  58.3%
5
  41.7%
48
  50.0%
1.Primary Outcome
Title AUC(0-∞) for Empagliflozin
Hide Description Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Pharmacokinetic set (PKS):

The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.

Arm/Group Title T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Hide Arm/Group Description:
Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin
Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
Overall Number of Participants Analyzed 24 24 24 24 24 24 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol * h/L
4330
(16.6%)
4110
(15.3%)
1680
(22.0%)
1630
(21.1%)
4200
(20.3%)
4060
(18.6%)
1610
(16.5%)
1560
(17.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T1 (FDC), R1 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 105.29
Confidence Interval (2-Sided) 90%
101.92 to 108.78
Parameter Dispersion
Type: Standard Deviation
Value: 6.6
Estimation Comments Ratio of the geometric means for treatments (Test (T1) versus Reference (R1)) i.e. T1/R1. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T2 (FDC), R2 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 103.23
Confidence Interval (2-Sided) 90%
99.91 to 106.65
Parameter Dispersion
Type: Standard Deviation
Value: 6.6
Estimation Comments Ratio of the geometric means for treatments (Test (T2) versus Reference (R2)) i.e. T2/R2. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T3 (FDC), R3 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 103.56
Confidence Interval (2-Sided) 90%
99.73 to 107.54
Parameter Dispersion
Type: Standard Deviation
Value: 7.6
Estimation Comments Ratio of the geometric means for treatments (Test (T3) versus Reference (R3)) i.e. T3/R3. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection T4 (FDC), R4 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 102.81
Confidence Interval (2-Sided) 90%
99.36 to 106.37
Parameter Dispersion
Type: Standard Deviation
Value: 6.9
Estimation Comments Ratio of the geometric means for treatments (Test (T4) versus Reference (R4)) i.e. T4/R4. The standard deviation is actually the intra-individual gCV.
2.Primary Outcome
Title AUC(0-∞) for Metformin
Hide Description Area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Pharmacokinetic set (PKS):

The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.

Arm/Group Title T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Hide Arm/Group Description:
Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin
Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
Overall Number of Participants Analyzed 24 24 24 24 24 24 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng * h/mL
11600
(18.9%)
11100
(17.4%)
11700
(21.8%)
11000
(24.0%)
7800
(18.9%)
7510
(17.8%)
7030
(20.7%)
7340
(18.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T1 (FDC), R1 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 104.56
Confidence Interval (2-Sided) 90%
97.56 to 112.07
Parameter Dispersion
Type: Standard Deviation
Value: 14.0
Estimation Comments Ratio of the geometric means for treatments (Test (T1) versus Reference (R1)) i.e. T1/R1. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T2 (FDC), R2 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 105.80
Confidence Interval (2-Sided) 90%
99.32 to 112.70
Parameter Dispersion
Type: Standard Deviation
Value: 12.8
Estimation Comments Ratio of the geometric means for treatments (Test (T2) versus Reference (R2)) i.e. T2/R2. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T3 (FDC), R3 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 103.75
Confidence Interval (2-Sided) 90%
98.18 to 109.63
Parameter Dispersion
Type: Standard Deviation
Value: 11.2
Estimation Comments Ratio of the geometric means for treatments (Test (T3) versus Reference (R3)) i.e. T3/R3. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection T4 (FDC), R4 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 95.77
Confidence Interval (2-Sided) 90%
89.88 to 102.03
Parameter Dispersion
Type: Standard Deviation
Value: 12.8
Estimation Comments Ratio of the geometric means for treatments (Test (T4) versus Reference (R4)) i.e. T4/R4. The standard deviation is actually the intra-individual gCV.
3.Primary Outcome
Title Cmax for Empagliflozin
Hide Description Maximum measured concentration of the empagliflozin in plasma
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Pharmacokinetic set (PKS):

The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.

Arm/Group Title T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Hide Arm/Group Description:
Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin
Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
Overall Number of Participants Analyzed 24 24 24 24 24 24 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
644
(18.2%)
605
(15.3%)
263
(17.7%)
237
(20.7%)
569
(22.1%)
561
(25.3%)
228
(16.4%)
221
(22.2%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T1 (FDC), R1 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 106.44
Confidence Interval (2-Sided) 90%
100.44 to 112.80
Parameter Dispersion
Type: Standard Deviation
Value: 11.8
Estimation Comments Ratio of the geometric means for treatments (Test (T1) versus Reference (R1)) i.e. T1/R1. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T2 (FDC), R2 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 110.78
Confidence Interval (2-Sided) 90%
103.80 to 118.24
Parameter Dispersion
Type: Standard Deviation
Value: 13.2
Estimation Comments Ratio of the geometric means for treatments (Test (T2) versus Reference (R2)) i.e. T2/R2. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T3 (FDC), R3 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 101.38
Confidence Interval (2-Sided) 90%
94.82 to 108.39
Parameter Dispersion
Type: Standard Deviation
Value: 13.6
Estimation Comments Ratio of the geometric means for treatments (Test (T3) versus Reference (R3)) i.e. T3/R3. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection T4 (FDC), R4 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 103.02
Confidence Interval (2-Sided) 90%
95.08 to 111.63
Parameter Dispersion
Type: Standard Deviation
Value: 16.3
Estimation Comments Ratio of the geometric means for treatments (Test (T4) versus Reference (R4)) i.e. T4/R4. The standard deviation is actually the intra-individual gCV.
4.Primary Outcome
Title Cmax for Metformin
Hide Description Maximum measured concentration of the metformin in plasma
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Pharmacokinetic set (PKS):

The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.

Arm/Group Title T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Hide Arm/Group Description:
Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin
Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
Overall Number of Participants Analyzed 24 24 24 24 24 24 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1920
(20.9%)
1830
(16.6%)
1950
(26.4%)
1840
(26.0%)
1290
(22.2%)
1230
(27.1%)
1150
(25.5%)
1190
(21.3%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T1 (FDC), R1 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 104.91
Confidence Interval (2-Sided) 90%
99.29 to 110.86
Parameter Dispersion
Type: Standard Deviation
Value: 11.2
Estimation Comments Ratio of the geometric means for treatments (Test (T1) versus Reference (R1)) i.e. T1/R1. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T2 (FDC), R2 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 106.32
Confidence Interval (2-Sided) 90%
98.39 to 114.88
Parameter Dispersion
Type: Standard Deviation
Value: 15.7
Estimation Comments Ratio of the geometric means for treatments (Test (T2) versus Reference (R2)) i.e. T2/R2. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T3 (FDC), R3 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 104.44
Confidence Interval (2-Sided) 90%
96.68 to 112.82
Parameter Dispersion
Type: Standard Deviation
Value: 15.7
Estimation Comments Ratio of the geometric means for treatments (Test (T3) versus Reference (R3)) i.e. T3/R3. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection T4 (FDC), R4 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 96.61
Confidence Interval (2-Sided) 90%
88.90 to 104.99
Parameter Dispersion
Type: Standard Deviation
Value: 16.9
Estimation Comments Ratio of the geometric means for treatments (Test (T4) versus Reference (R4)) i.e. T4/R4. The standard deviation is actually the intra-individual gCV.
5.Secondary Outcome
Title AUC(0-tz) of Empagliflozin
Hide Description Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 up to the last quantifiable data point
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Pharmacokinetic set (PKS):

The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.

Arm/Group Title T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Hide Arm/Group Description:
Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin
Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
Overall Number of Participants Analyzed 24 24 24 24 24 24 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol * h/L
4270
(16.6%)
4060
(14.7%)
1650
(21.5%)
1600
(21.0%)
4140
(19.7%)
4010
(18.5%)
1580
(16.7%)
1540
(17.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T1 (FDC), R1 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 105.16
Confidence Interval (2-Sided) 90%
101.97 to 108.45
Parameter Dispersion
Type: Standard Deviation
Value: 6.2
Estimation Comments Ratio of the geometric means for treatments (Test (T1) versus Reference (R1)) i.e. T1/R1. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T2 (FDC), R2 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 103.07
Confidence Interval (2-Sided) 90%
99.75 to 106.50
Parameter Dispersion
Type: Standard Deviation
Value: 6.6
Estimation Comments Ratio of the geometric means for treatments (Test (T2) versus Reference (R2)) i.e. T2/R2. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T3 (FDC), R3 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 103.14
Confidence Interval (2-Sided) 90%
99.37 to 107.04
Parameter Dispersion
Type: Standard Deviation
Value: 7.5
Estimation Comments Ratio of the geometric means for treatments (Test (T3) versus Reference (R3)) i.e. T3/R3. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection T4 (FDC), R4 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 102.61
Confidence Interval (2-Sided) 90%
99.10 to 106.25
Parameter Dispersion
Type: Standard Deviation
Value: 7.0
Estimation Comments Ratio of the geometric means for treatments (Test (T4) versus Reference (R4)) i.e. T4/R4. The standard deviation is actually the intra-individual gCV.
6.Secondary Outcome
Title AUC(0-tz) of Metformin
Hide Description Area under the concentration-time curve of the metformin in plasma over the time interval from 0 up to the last quantifiable data point
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Pharmacokinetic set (PKS):

The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.

Arm/Group Title T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Hide Arm/Group Description:
Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin
Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg
Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg
Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin
Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
Overall Number of Participants Analyzed 24 24 24 24 24 24 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng* h/mL
11400
(19.2%)
10800
(17.6%)
11400
(23.1%)
10800
(25.1%)
7630
(18.9%)
7420
(17.9%)
6790
(24.7%)
7230
(18.3%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T1 (FDC), R1 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 105.33
Confidence Interval (2-Sided) 90%
99.34 to 111.68
Parameter Dispersion
Type: Standard Deviation
Value: 11.9
Estimation Comments Ratio of the geometric means for treatments (Test (T1) versus Reference (R1)) i.e. T1/R1. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T2 (FDC), R2 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 105.75
Confidence Interval (2-Sided) 90%
99.09 to 112.85
Parameter Dispersion
Type: Standard Deviation
Value: 13.2
Estimation Comments Ratio of the geometric means for treatments (Test (T2) versus Reference (R2)) i.e. T2/R2. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T3 (FDC), R3 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 102.90
Confidence Interval (2-Sided) 90%
97.11 to 109.03
Parameter Dispersion
Type: Standard Deviation
Value: 11.7
Estimation Comments Ratio of the geometric means for treatments (Test (T3) versus Reference (R3)) i.e. T3/R3. The standard deviation is actually the intra-individual gCV.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection T4 (FDC), R4 (FC)
Comments

The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:

‘sequence’, ‘subjects within sequences’, ‘period’ and ‘treatment’. The effect ‘subjects within sequences’ was considered as random, whereas the other effects were considered as fixed.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments P-value for ratio outside interval 80-125
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the geometric means
Estimated Value 93.84
Confidence Interval (2-Sided) 90%
87.74 to 100.36
Parameter Dispersion
Type: Standard Deviation
Value: 13.6
Estimation Comments Ratio of the geometric means for treatments (Test (T4) versus Reference (R4)) i.e. T4/R4. The standard deviation is actually the intra-individual gCV.
Time Frame First drug administration until 7 days after last drug administration, up to 8 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Hide Arm/Group Description Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
All-Cause Mortality
T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/24 (0.00%)   0/24 (0.00%)   0/24 (0.00%)   0/24 (0.00%)   0/24 (0.00%)   0/24 (0.00%)   0/24 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
T1 (FDC) R1 (FC) T2 (FDC) R2 (FC) T3 (FDC) R3 (FC) T4 (FDC) R4 (FC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/24 (33.33%)   8/24 (33.33%)   9/24 (37.50%)   11/24 (45.83%)   12/24 (50.00%)   11/24 (45.83%)   7/24 (29.17%)   9/24 (37.50%) 
Gastrointestinal disorders                 
Abdominal pain upper  1  1/24 (4.17%)  2/24 (8.33%)  1/24 (4.17%)  0/24 (0.00%)  1/24 (4.17%)  2/24 (8.33%)  2/24 (8.33%)  2/24 (8.33%) 
Diarrhoea  1  5/24 (20.83%)  4/24 (16.67%)  7/24 (29.17%)  11/24 (45.83%)  10/24 (41.67%)  8/24 (33.33%)  3/24 (12.50%)  5/24 (20.83%) 
Nausea  1  1/24 (4.17%)  2/24 (8.33%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  3/24 (12.50%)  1/24 (4.17%) 
Vomiting  1  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  2/24 (8.33%) 
Investigations                 
Bilirubin conjugated increased  1  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  2/24 (8.33%)  3/24 (12.50%) 
Blood bilirubin increased  1  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  2/24 (8.33%)  3/24 (12.50%) 
Blood bilirubin unconjugated increased  1  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  2/24 (8.33%) 
Glucose urine present  1  3/24 (12.50%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Nervous system disorders                 
Dizziness  1  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 800-243-0127 ext +1
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02102932     History of Changes
Other Study ID Numbers: 1276.23
First Submitted: March 31, 2014
First Posted: April 3, 2014
Results First Submitted: August 21, 2015
Results First Posted: September 24, 2015
Last Update Posted: September 24, 2015