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12 Week Efficacy and Safety Study of Empagliflozin (BI 10773) in Hypertensive Patients With Type 2 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01370005
Recruitment Status : Completed
First Posted : June 9, 2011
Results First Posted : June 17, 2014
Last Update Posted : February 22, 2016
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Conditions Diabetes Mellitus, Type 2
Hypertension
Interventions Drug: Placebo
Drug: BI 10773
Enrollment 825
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks. Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks. Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Period Title: Overall Study
Started 272 276 277
Completed 256 265 266
Not Completed 16 11 11
Reason Not Completed
Not treated             1             0             0
Adverse Event             5             5             6
Lack of Efficacy             1             0             0
Non compliant with protocol             0             1             2
Lost to Follow-up             1             1             1
Patient refusal to continue,not due toAE             5             4             0
Other reason not defined above             3             0             2
Arm/Group Title Placebo Empa 10mg Empa 25mg Total
Hide Arm/Group Description A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks. Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks. Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 271 276 276 823
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomised and treated patients who had a baseline HbA1c value and a baseline mean 24-h SBP value. Treatment assignment as randomized
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 271 participants 276 participants 276 participants 823 participants
60.3  (8.8) 60.6  (8.5) 59.9  (9.7) 60.2  (9.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 271 participants 276 participants 276 participants 823 participants
Female
103
  38.0%
105
  38.0%
120
  43.5%
328
  39.9%
Male
168
  62.0%
171
  62.0%
156
  56.5%
495
  60.1%
1.Primary Outcome
Title HbA1c Change From Baseline
Hide Description Change from baseline in HbA1c after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (FAS), which included all randomised and treated patients who had a baseline HbA1c and a baseline mean 24-h systolic blood pressure value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: percentage of HbA1c
0.03  (0.60) -0.59  (0.63) -0.63  (0.62)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments Hierarchical testing structure was: 1) Change from baseline to week 12 in HbA1c, empa 25mg vs placebo 2) Change from baseline to week 12 in mean 24h SBP, empa 25mg vs placebo 3) Change from baseline to week 12 in HbA1c, empa 10mg vs placebo 4) Change from baseline in mean 24h SBP, empa 10mg vs placebo 5) Change from baseline in mean 24h DBP, empa 25mg vs placebo 6) Change from baseline in mean 24h DBP empa 10mg vs placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing, no adjustment of p-values.
Method ANCOVA
Comments Model includes baseline HbA1c as lin. covariate and treatment, baseline renal function, region and baseline N of antihyperten. med. as fixed effects
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.62
Confidence Interval (2-Sided) 95%
-0.72 to -0.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.05
Estimation Comments Difference calculated as empa 10mg minus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments Hierarchical testing structure was: 1) Change from baseline to week 12 in HbA1c, empa 25mg vs placebo 2) Change from baseline to week 12 in mean 24h SBP, empa 25mg vs placebo 3) Change from baseline to week 12 in HbA1c, empa 10mg vs placebo 4) Change from baseline in mean 24h SBP, empa 10mg vs placebo 5) Change from baseline in mean 24h DBP, empa 25mg vs placebo 6) Change from baseline in mean 24h DBP empa 10mg vs placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing, no adjustment of p-values
Method ANCOVA
Comments Model includes baseline HbA1c as lin. covariate and treatment, baseline renal function, region and baseline N of antihyperten. med. as fixed effects
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-0.75 to -0.55
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.05
Estimation Comments Difference calculated as empa 25mg minus placebo
2.Primary Outcome
Title Mean 24-hour Systolic Blood Pressure Change From Baseline
Hide Description Change from baseline of mean 24-hour systolic blood pressure (SBP).
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

FAS, which included all randomised and treated patients who had a baseline HbA1c and a baseline mean 24-h systolic blood pressure value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: mmHg
0.42  (8.25) -2.99  (8.86) -3.59  (9.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments Hierarchical testing structure was: 1) Change from baseline to week 12 in HbA1c, empa 25mg vs placebo 2) Change from baseline to week 12 in mean 24h SBP, empa 25mg vs placebo 3) Change from baseline to week 12 in HbA1c, empa 10mg vs placebo 4) Change from baseline in mean 24h SBP, empa 10mg vs placebo 5) Change from baseline in mean 24h DBP, empa 25mg vs placebo 6) Change from baseline in mean 24h DBP empa 10mg vs placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing, no adjustment of p-values.
Method ANCOVA
Comments Model incl. baseline (bl) HbA1c, bl mean 24h SBP as lin. covariates; treatment, bl renal function, region, bl N of antihyperten. med. as fixed effects
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.44
Confidence Interval (2-Sided) 95%
-4.78 to -2.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.69
Estimation Comments Difference calculated as empa 10mg minus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments Hierarchical testing structure was: 1) Change from baseline to week 12 in HbA1c, empa 25mg vs placebo 2) Change from baseline to week 12 in mean 24h SBP, empa 25mg vs placebo 3) Change from baseline to week 12 in HbA1c, empa 10mg vs placebo 4) Change from baseline in mean 24h SBP, empa 10mg vs placebo 5) Change from baseline in mean 24h DBP, empa 25mg vs placebo 6) Change from baseline in mean 24h DBP empa 10mg vs placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing, no adjustment of p-values.
Method ANCOVA
Comments Model incl. baseline (bl) HbA1c, bl mean 24h SBP as lin. covariates; treatment, bl renal function, region, bl N of antihyperten. med. as fixed effects
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.16
Confidence Interval (2-Sided) 95%
-5.50 to -2.83
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.68
Estimation Comments Difference calculated as empa 25mg minus placebo
3.Secondary Outcome
Title Mean 24-hour Diastolic Blood Pressure Change From Baseline
Hide Description Change from baseline in mean 24-hour diastolic blood pressure (DBP) after 12 weeks.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

FAS which included all randomised and treated patients who had a baseline HbA1c and a baseline mean 24-h systolic blood pressure value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: mmHg
0.30  (5.06) -1.10  (4.96) -1.32  (4.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments Hierarchical testing structure was: 1) Change from baseline to week 12 in HbA1c, empa 25mg vs placebo 2) Change from baseline to week 12 in mean 24h SBP, empa 25mg vs placebo 3) Change from baseline to week 12 in HbA1c, empa 10mg vs placebo 4) Change from baseline in mean 24h SBP, empa 10mg vs placebo 5) Change from baseline in mean 24h DBP, empa 25mg vs placebo 6) Change from baseline in mean 24h DBP empa 10mg vs placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments Hierarchical testing, no adjustment of p-values.
Method ANCOVA
Comments Model incl. baseline (bl) HbA1c, bl mean 24h DBP as lin. covariates; treatment, bl renal function, region, bl N of antihyperten. med. as fixed effects
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.36
Confidence Interval (2-Sided) 95%
-2.15 to -0.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.40
Estimation Comments Difference calculated as empa 10mg minus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments Hierarchical testing structure was: 1) Change from baseline to week 12 in HbA1c, empa 25mg vs placebo 2) Change from baseline to week 12 in mean 24h SBP, empa 25mg vs placebo 3) Change from baseline to week 12 in HbA1c, empa 10mg vs placebo 4) Change from baseline in mean 24h SBP, empa 10mg vs placebo 5) Change from baseline in mean 24h DBP, empa 25mg vs placebo 6) Change from baseline in mean 24h DBP empa 10mg vs placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing, no adjustment of p-values.
Method ANCOVA
Comments Model incl. baseline (bl) HbA1c, bl mean 24h DBP as lin. covariates; treatment, bl renal function, region, bl N of antihyperten. med. as fixed effects
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.72
Confidence Interval (2-Sided) 95%
-2.51 to -0.93
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.40
Estimation Comments Difference calculated as empa 25mg minus placebo
4.Secondary Outcome
Title Proportion of Patients With HbA1c <7%
Hide Description Proportion of patients with HbA1c <7% after 12 weeks.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Patients in the full analysis set (FAS) and with baseline HbA1c >= 7%. Treatment assignment as randomised.

Non-completers (missing data due to early discontinuation or values after start of rescue medication) considered 'failure' was used as the imputation rule.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 252 256 264
Measure Type: Number
Unit of Measure: participants
18 79 79
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model includes treatment, baseline renal function, region, baseline number of antihypertensive medications and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.26
Confidence Interval (2-Sided) 95%
3.51 to 11.18
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model includes treatment, baseline renal function, region, baseline number of antihypertensive medications and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.59
Confidence Interval (2-Sided) 95%
3.70 to 11.75
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Fasting Plasma Glucose (FPG) Change From Baseline
Hide Description Change from baseline in FPG after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (FAS) which included all randomised and treated patients who had a baseline HbA1c value and a baseline mean 24-h systolic blood pressure (SBP) value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: mg/dL
7.19  (38.29) -15.23  (33.32) -24.45  (35.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline FPG
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -23.76
Confidence Interval (2-Sided) 95%
-28.91 to -18.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.63
Estimation Comments Difference calculated as empa 10mg minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline FPG
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -30.20
Confidence Interval (2-Sided) 95%
-35.32 to -25.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.61
Estimation Comments Difference calculated as empa 25mg minus placebo.
6.Secondary Outcome
Title Body Weight Change From Baseline
Hide Description Change from baseline in body weight after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Full analysis set (FAS) which included all randomised and treated patients who had a baseline HbA1c value and a baseline mean 24-h systolic blood pressure (SBP) value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: kg
-0.19  (1.55) -1.67  (2.38) -2.16  (2.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline number of antihypertensive med., baseline HbA1c and baseline weight
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.49
Confidence Interval (2-Sided) 95%
-1.85 to -1.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.18
Estimation Comments Difference calculated as empa 10mg minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline number of antihypertensive med., baseline HbA1c and baseline weight
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.98
Confidence Interval (2-Sided) 95%
-2.33 to -1.62
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.18
Estimation Comments Difference calculated as empa 10mg minus placebo.
7.Secondary Outcome
Title Daytime Mean Systolic Blood Pressure (SBP) Change From Baseline
Hide Description Change from baseline in daytime mean SBP after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

FAS which included all randomised and treated patients who had a baseline HbA1c value and a baseline mean 24-h systolic blood pressure (SBP) value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: mmHg
0.38  (8.74) -3.40  (9.55) -4.12  (9.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, N of antihypertensive medications, baseline HbA1c and baseline daytime SBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.94
Confidence Interval (2-Sided) 95%
-5.37 to -2.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.73
Estimation Comments Difference calculated as empa 10mg minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline daytime SBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.78
Confidence Interval (2-Sided) 95%
-6.20 to -3.36
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.72
Estimation Comments Difference calculated as empa 25mg minus placebo.
8.Secondary Outcome
Title Daytime Mean Diastolic Blood Pressure (DBP) Change From Baseline
Hide Description Change from baseline in daytime mean DBP after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

FAS which included all randomised and treated patients who had a baseline HbA1c value and a baseline mean 24-h systolic blood pressure (SBP) value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: mmHg
0.26  (5.36) -1.28  (5.41) -1.58  (5.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline daytime DBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.56
Confidence Interval (2-Sided) 95%
-2.42 to -0.69
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.44
Estimation Comments Difference calculated as empa 10mg minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline daytime DBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.98
Confidence Interval (2-Sided) 95%
-2.84 to -1.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.44
Estimation Comments Difference calculated as empa 25mg minus placebo.
9.Secondary Outcome
Title Nighttime Mean Systolic Blood Pressure (SBP) Change From Baseline
Hide Description Change from baseline in nighttime mean SBP after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

FAS which included all randomised and treated patients who had a baseline HbA1c value and a baseline mean 24-h systolic blood pressure (SBP) value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: mmHg
0.51  (10.22) -2.22  (10.21) -2.47  (11.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline night-time SBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.50
Confidence Interval (2-Sided) 95%
-4.09 to -0.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.81
Estimation Comments Difference calculated as empa 10mg minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline night-time SBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.90
Confidence Interval (2-Sided) 95%
-4.48 to -1.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.81
Estimation Comments Difference calculated as empa 25mg minus placebo.
10.Secondary Outcome
Title Nighttime Mean Diastolic Blood Pressure (DBP) Change From Baseline
Hide Description Change from baseline in nighttime mean DBP after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

FAS which included all randomised and treated patients who had a baseline HbA1c value and a baseline mean 24-h systolic blood pressure (SBP) value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: mmHg
0.36  (6.80) -0.80  (6.21) -0.75  (6.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0566
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline night-time DBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.95
Confidence Interval (2-Sided) 95%
-1.93 to 0.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.50
Estimation Comments Difference calculated as empa 10mg minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0208
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline night-time DBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.15
Confidence Interval (2-Sided) 95%
-2.12 to -0.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.50
Estimation Comments Difference calculated as empa 25mg minus placebo.
11.Secondary Outcome
Title Trough Mean Seated Systolic Blood Pressure (SBP) Change From Baseline
Hide Description Change from baseline in Trough Mean Seated SBP after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

FAS which included all randomised and treated patients who had a baseline HbA1c value and a baseline mean 24-h systolic blood pressure (SBP) value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: mmHg
-0.57  (11.92) -4.73  (12.54) -5.45  (12.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline seated SBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.92
Confidence Interval (2-Sided) 95%
-5.86 to -1.98
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.99
Estimation Comments Difference calculated as empa 10mg minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline seated SBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.80
Confidence Interval (2-Sided) 95%
-6.73 to -2.87
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.98
Estimation Comments Difference calculated as empa 25mg minus placebo.
12.Secondary Outcome
Title Trough Mean Seated Diastolic Blood Pressure (DBP) Change From Baseline
Hide Description Change from baseline in trough mean seated DBP after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

FAS which included all randomised and treated patients who had a baseline HbA1c value and a baseline mean 24-h systolic blood pressure (SBP) value. Treatment assignment as randomised.

Values after start of antidiabetic rescue therapy or change of antihypertensive therapy were set to missing and LOCF was used for imputation of missing values.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Mean (Standard Deviation)
Unit of Measure: mmHg
-1.02  (6.58) -3.18  (7.10) -3.01  (7.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline seated DBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.93
Confidence Interval (2-Sided) 95%
-3.01 to -0.84
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.55
Estimation Comments Difference calculated as empa 10mg minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method ANCOVA
Comments Model includes treatment, baseline renal function, geographical region, baseline N of antihyperten. med., baseline HbA1c and baseline seated DBP
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.89
Confidence Interval (2-Sided) 95%
-2.97 to -0.82
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.55
Estimation Comments Difference calculated as empa 25mg minus placebo.
13.Secondary Outcome
Title Proportion of Patients Reaching Blood Pressure <130/80 mmHg
Hide Description Proportion of patients reaching blood pressure <130/80 mmHg after 12 weeks of treatment
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Patients in the FAS without blood pressure control at baseline. Blood pressure control is defined as DBP<80 mmHg and SBP <130 mmHg. Treatment assignment as randomised.

Non-completers (missing data due to early disc, values after start of rescue medication or changes in antihyp. therapy) considered 'failure' was used as the imputation rule.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 241 251 247
Measure Type: Number
Unit of Measure: participants
19 45 40
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 10mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model includes treatment, baseline renal function, region, baseline number of antihypertensive medications and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.49
Confidence Interval (2-Sided) 95%
1.39 to 4.45
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Empa 25mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0088
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model includes treatment, baseline renal function, region, baseline number of antihypertensive medications and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.20
Confidence Interval (2-Sided) 95%
1.22 to 3.96
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Composite Endpoint of Change From Baseline of HbA1c, Systolic Blood Pressure and Body Weight
Hide Description A composite endpoint of the following conditions at week 12 compared to baseline (all 3 fulfilled): reduction of HbA1c from baseline of at least 0.5%, reduction of systolic blood pressure > 3 mmHg from baseline and reduction of weight from baseline > 2%
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Patients in the full analysis set (FAS). Treatment assignment as randomised.

Non-completers (missing data due to early discontinuation, values after start of rescue medication or changes in antihypertensive therapy) considered 'failure' was used as the imputation rule.

Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 271 276 276
Measure Type: Number
Unit of Measure: participants
Number fulfilled 6 41 58
Number not fulfilled 265 235 218
15.Secondary Outcome
Title Orthostatic Blood Pressure
Hide Description Orthostatic blood pressure (BP) at baseline and after 12 weeks of treatment.
Time Frame Baseline and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set for patients with available measurements at baseline and week 12. Treatment assignment as first medication taken.
Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 254 259 259
Measure Type: Number
Unit of Measure: participants
Baseline: Positive 42 40 51
Baseline: Negative 212 219 208
Week 12: Positive 51 67 76
Week 12: Negative 203 192 183
16.Other Pre-specified Outcome
Title Confirmed Hypoglycaemic Adverse Events
Hide Description Number of participants with confirmed hypoglycaemic adverse events
Time Frame From drug administration until last drug administration plus seven days, up to 171 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set which included all patients treated with at least one dose of randomised trial medication. Treatment assignment as first medication taken.
Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description:
A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks.
Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
Overall Number of Participants Analyzed 272 276 276
Measure Type: Number
Unit of Measure: participants
13 18 17
Time Frame From drug administration until last drug administration plus seven days, up to 171 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Empa 10mg Empa 25mg
Hide Arm/Group Description A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 12 weeks. Single oral dose of empagliflozin (empa) 10mg taken once daily for 12 weeks. Single oral dose of empagliflozin (empa) 25mg taken once daily for 12 weeks.
All-Cause Mortality
Placebo Empa 10mg Empa 25mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Empa 10mg Empa 25mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/272 (2.57%)   3/276 (1.09%)   4/276 (1.45%) 
Cardiac disorders       
Angina pectoris  1  1/272 (0.37%)  0/276 (0.00%)  0/276 (0.00%) 
Ear and labyrinth disorders       
Acute vestibular syndrome  1  1/272 (0.37%)  0/276 (0.00%)  0/276 (0.00%) 
Gastrointestinal disorders       
Constipation  1  1/272 (0.37%)  0/276 (0.00%)  0/276 (0.00%) 
General disorders       
Chest pain  1  0/272 (0.00%)  0/276 (0.00%)  1/276 (0.36%) 
Sudden death  1  0/272 (0.00%)  1/276 (0.36%)  0/276 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  0/272 (0.00%)  0/276 (0.00%)  1/276 (0.36%) 
Cholecystitis acute  1  1/272 (0.37%)  0/276 (0.00%)  0/276 (0.00%) 
Infections and infestations       
Osteomyelitis  1  0/272 (0.00%)  1/276 (0.36%)  0/276 (0.00%) 
Pneumonia  1  0/272 (0.00%)  0/276 (0.00%)  1/276 (0.36%) 
Injury, poisoning and procedural complications       
Traumatic fracture  1  1/272 (0.37%)  0/276 (0.00%)  0/276 (0.00%) 
Investigations       
Electrocardiogram T wave inversion  1  0/272 (0.00%)  0/276 (0.00%)  1/276 (0.36%) 
Metabolism and nutrition disorders       
Diabetic ketoacidosis  1  1/272 (0.37%)  0/276 (0.00%)  0/276 (0.00%) 
Nervous system disorders       
Carotid artery thrombosis  1  0/272 (0.00%)  0/276 (0.00%)  1/276 (0.36%) 
Dizziness  1  0/272 (0.00%)  1/276 (0.36%)  0/276 (0.00%) 
Renal and urinary disorders       
Urethral stenosis  1  1/272 (0.37%)  0/276 (0.00%)  0/276 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Empa 10mg Empa 25mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   43/272 (15.81%)   42/276 (15.22%)   55/276 (19.93%) 
General disorders       
Thirst  1  1/272 (0.37%)  2/276 (0.72%)  15/276 (5.43%) 
Infections and infestations       
Nasopharyngitis  1  26/272 (9.56%)  15/276 (5.43%)  20/276 (7.25%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  14/272 (5.15%)  19/276 (6.88%)  19/276 (6.88%) 
Renal and urinary disorders       
Pollakiuria  1  7/272 (2.57%)  11/276 (3.99%)  17/276 (6.16%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.0
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.
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01370005     History of Changes
Other Study ID Numbers: 1245.48
2011-000347-25 ( EudraCT Number: EudraCT )
First Submitted: June 8, 2011
First Posted: June 9, 2011
Results First Submitted: May 16, 2014
Results First Posted: June 17, 2014
Last Update Posted: February 22, 2016