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Demonstration of Bioequivalence of Empagliflozin and Metformin Given in One Tablet Compared to the Intake of Single Tablets

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ClinicalTrials.gov Identifier: NCT01672788
Recruitment Status : Completed
First Posted : August 27, 2012
Results First Posted : August 31, 2015
Last Update Posted : August 31, 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 Healthy
Interventions Drug: Empagliflozin
Drug: Empagliflozin + Metformin
Drug: Metformin
Enrollment 36
Recruitment Details  
Pre-assignment Details This was an open-label, randomized, 4-way crossover trial. 36 patients were randomised to one of 4 treatment sequences and treated. Each treatment period consisted of a single dose of medication followed by 72 hours of pharmacokinetic sampling, with a washout of at least 7 days between treatment periods.
Arm/Group Title T1 / R1 / T2 / R2 R1 / T1 / R2 / T2 T2 / R2 / T1 / R1 R2 / T2 / R1 / T1
Hide Arm/Group Description

Patients received the 4 treatments in the following order:

  • Empa 12.5mg Fixed-dose: Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin (T1)
  • Empa 12.5mg Free Dose: Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet) (R1)
  • Empa 5mg Fixed-dose: Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin (T2)
  • Empa 5mg Free Dose: Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) (R2)

Patients received the 4 treatments in the following order:

  • Empa 12.5mg Free Dose: Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet) (R1)
  • Empa 12.5mg Fixed-dose: Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin (T1)
  • Empa 5mg Free Dose: Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) (R2)
  • Empa 5mg Fixed-dose: Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin (T2)

Patients received the 4 treatments in the following order:

  • Empa 5mg Fixed-dose: Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin (T2)
  • Empa 5mg Free Dose: Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) (R2)
  • Empa 12.5mg Fixed-dose: Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin (T1)
  • Empa 12.5mg Free Dose: Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet) (R1)

Patients received the 4 treatments in the following order:

  • Empa 5mg Free Dose: Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) (R2)
  • Empa 5mg Fixed-dose: Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin (T2)
  • Empa 12.5mg Free Dose: Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet) (R1)
  • Empa 12.5mg Fixed-dose: Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin (T1)
Period Title: Treatment Period 1 (3 Days)
Started 9 9 9 9
Completed 9 9 9 9
Not Completed 0 0 0 0
Period Title: Washout Period 1 (7 Days)
Started 9 9 9 9
Completed 9 9 9 9
Not Completed 0 0 0 0
Period Title: Treatment Period 2 (3 Days)
Started 9 9 9 9
Completed 9 9 9 9
Not Completed 0 0 0 0
Period Title: Washout Period 2 (7 Days)
Started 9 9 9 9
Completed 9 9 9 8
Not Completed 0 0 0 1
Reason Not Completed
Adverse Event             0             0             0             1
Period Title: Treatment Period 3 (3 Days)
Started 9 9 9 8
Completed 9 9 9 8
Not Completed 0 0 0 0
Period Title: Washout Period 3 (7 Days)
Started 9 9 9 8
Completed 9 9 9 8
Not Completed 0 0 0 0
Period Title: Treatment Period 4 (3 Days)
Started 9 9 9 8
Completed 9 9 9 8
Not Completed 0 0 0 0
Arm/Group Title Overall Study
Hide Arm/Group Description Total number of patients randomised and treated in the study. This was an open-label, randomized, 4-way crossover trial. 36 patients were randomised to one of 4 treatment sequences and treated. Each treatment period consisted of a single dose of medication followed by 72hours of pharmacokinetic sampling, with a washout of at least 7 days between treatment periods.
Overall Number of Baseline Participants 36
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants
33.6  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants
Female
14
  38.9%
Male
22
  61.1%
1.Primary Outcome
Title Empa: Area Under the Curve 0 to Infinity (AUC0-∞)
Hide Description

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

In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
Arm/Group Title Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Hide Arm/Group Description:
Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin
Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet)
Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin
Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet)
Overall Number of Participants Analyzed 34 34 35 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
2560
(25.5%)
2530
(29.5%)
986
(26.9%)
968
(23.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg Fixed-dose, Empa 12.5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 12.5mg fixed-dose divided by empa 12.5mg free dose
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 101.31
Confidence Interval (2-Sided) 90%
96.89 to 105.93
Parameter Dispersion
Type: Standard Deviation
Value: 10.7
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 5mg Fixed-dose, Empa 5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 5mg fixed-dose divided by empa 5mg free dose
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 100.30
Confidence Interval (2-Sided) 90%
97.40 to 103.29
Parameter Dispersion
Type: Standard Deviation
Value: 7.0
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
2.Primary Outcome
Title Metformin: Area Under the Curve 0 to Infinity (AUC0-∞)
Hide Description

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

In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
Arm/Group Title Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Hide Arm/Group Description:
Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin
Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet)
Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin
Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet)
Overall Number of Participants Analyzed 34 34 35 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
8640
(18.0%)
8450
(24.4%)
8520
(23.8%)
8560
(25.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg Fixed-dose, Empa 12.5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 12.5mg fixed-dose divided by empa 12.5mg free dose.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 101.61
Confidence Interval (2-Sided) 90%
97.94 to 105.41
Parameter Dispersion
Type: Standard Deviation
Value: 8.8
Estimation Comments Standard deviation is actually the gCV
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 5mg Fixed-dose, Empa 5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 5mg fixed-dose divided by empa 5mg free dose.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 98.56
Confidence Interval (2-Sided) 90%
94.24 to 103.08
Parameter Dispersion
Type: Standard Deviation
Value: 10.8
Estimation Comments Standard deviation is actually the gCV
3.Primary Outcome
Title Empa: Maximum Measured Concentration (Cmax)
Hide Description

Maximum measured concentration of the analyte in plasma, per period.

In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
Arm/Group Title Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Hide Arm/Group Description:
Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin
Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet)
Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin
Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet)
Overall Number of Participants Analyzed 34 34 35 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
266
(20.3%)
258
(21.3%)
103
(22.1%)
101
(24.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg Fixed-dose, Empa 12.5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 12.5mg fixed-dose divided by empa 12.5mg free dose
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 102.70
Confidence Interval (2-Sided) 90%
98.75 to 106.81
Parameter Dispersion
Type: Standard Deviation
Value: 9.4
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 5mg Fixed-dose, Empa 5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 5mg fixed-dose divided by empa 5mg free dose
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 100.97
Confidence Interval (2-Sided) 90%
95.94 to 106.27
Parameter Dispersion
Type: Standard Deviation
Value: 12.3
Estimation Comments Standard deviation is actually the gCV
4.Primary Outcome
Title Metformin: Maximum Measured Concentration (Cmax)
Hide Description

Maximum measured concentration of the analyte in plasma, per period.

In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
Arm/Group Title Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Hide Arm/Group Description:
Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin
Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet)
Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin
Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet)
Overall Number of Participants Analyzed 34 34 35 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1080
(16.4%)
1080
(19.6%)
1090
(16.5%)
1100
(17.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg Fixed-dose, Empa 12.5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 12.5mg fixed-dose divided by empa 12.5mg free dose .
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 99.64
Confidence Interval (2-Sided) 90%
95.39 to 104.09
Parameter Dispersion
Type: Standard Deviation
Value: 10.5
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 5mg Fixed-dose, Empa 5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 5mg fixed-dose divided by empa 5mg free dose.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 97.89
Confidence Interval (2-Sided) 90%
93.82 to 102.15
Parameter Dispersion
Type: Standard Deviation
Value: 10.2
Estimation Comments Standard deviation is actually the 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 the analyte in plasma over the time interval from 0 to the last quantifiable data point.

In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
Arm/Group Title Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Hide Arm/Group Description:
Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin
Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet)
Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin
Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet)
Overall Number of Participants Analyzed 34 34 35 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
2520
(25.1%)
2490
(29.3%)
963
(27.1%)
946
(24.2%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg Fixed-dose, Empa 12.5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 12.5mg fixed-dose divided by empa 12.5mg free dose
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 101.20
Confidence Interval (2-Sided) 90%
96.89 to 105.71
Parameter Dispersion
Type: Standard Deviation
Value: 10.4
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 5mg Fixed-dose, Empa 5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 5mg fixed-dose divided by empa 5mg free dose
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 100.31
Confidence Interval (2-Sided) 90%
97.41 to 103.30
Parameter Dispersion
Type: Standard Deviation
Value: 7.0
Estimation Comments Standard deviation is actually the 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 the analyte in plasma over the time interval from 0 to the last quantifiable data point.

In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
Arm/Group Title Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Hide Arm/Group Description:
Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin
Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet)
Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin
Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet)
Overall Number of Participants Analyzed 34 34 35 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
8370
(18.1%)
8190
(24.1%)
8280
(23.2%)
8320
(25.2%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg Fixed-dose, Empa 12.5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 12.5mg fixed-dose divided by empa 12.5mg free dose .
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 101.51
Confidence Interval (2-Sided) 90%
97.95 to 105.21
Parameter Dispersion
Type: Standard Deviation
Value: 8.6
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 5mg Fixed-dose, Empa 5mg Free Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Considered characteristic is empa 5mg fixed-dose divided by empa 5mg free dose .
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 98.57
Confidence Interval (2-Sided) 90%
94.50 to 102.81
Parameter Dispersion
Type: Standard Deviation
Value: 10.1
Estimation Comments Standard deviation is actually the gCV
Time Frame Treatment period and following washout period, up to 35 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Hide Arm/Group Description Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet) Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet)
All-Cause Mortality
Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)   0/36 (0.00%)   0/34 (0.00%)   0/35 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Empa 12.5mg Fixed-dose Empa 12.5mg Free Dose Empa 5mg Fixed-dose Empa 5mg Free Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/35 (40.00%)   13/36 (36.11%)   14/34 (41.18%)   9/35 (25.71%) 
Gastrointestinal disorders         
Diarrhoea  1  8/35 (22.86%)  8/36 (22.22%)  5/34 (14.71%)  7/35 (20.00%) 
Nausea  1  3/35 (8.57%)  1/36 (2.78%)  0/34 (0.00%)  1/35 (2.86%) 
Vomiting  1  2/35 (5.71%)  1/36 (2.78%)  0/34 (0.00%)  1/35 (2.86%) 
Nasopharyngitis  1  3/35 (8.57%)  2/36 (5.56%)  4/34 (11.76%)  0/35 (0.00%) 
Nervous system disorders         
Headache  1  5/35 (14.29%)  3/36 (8.33%)  5/34 (14.71%)  2/35 (5.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.1
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
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01672788     History of Changes
Other Study ID Numbers: 1276.7
2012-002277-65 ( EudraCT Number: EudraCT )
First Submitted: August 22, 2012
First Posted: August 27, 2012
Results First Submitted: June 26, 2015
Results First Posted: August 31, 2015
Last Update Posted: August 31, 2015