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A 16 Weeks Study on Efficacy and Safety of Two Doses of Empagliflozin (BI 10773) (Once Daily Versus Twice Daily) in Patients With Type 2 Diabetes Mellitus and Preexisting Metformin Therapy

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ClinicalTrials.gov Identifier: NCT01649297
Recruitment Status : Completed
First Posted : July 25, 2012
Results First Posted : July 23, 2015
Last Update Posted : July 23, 2015
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
Condition Diabetes Mellitus, Type 2
Interventions Drug: Placebo
Drug: empagliflozin (low dose qd)
Drug: Empagliflozin (high dose qd)
Drug: empagliflozin (high dose bid)
Drug: empagliflozin (low dose bid)
Enrollment 983
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Empa 12.5mg BID Empa 25mg QD Empa 5mg BID Empa 10mg QD Placebo
Hide Arm/Group Description Oral administration of Empagliflozin (Empa) 12.5 mg twice daily (BID) Oral administration of Empagliflozin (Empa) 25 mg once daily (QD) Oral administration of Empagliflozin (Empa) 5 mg twice daily (BID) Oral administration of Empagliflozin (Empa) 10 mg once daily (QD) Oral administration of Placebo tablets matching empagliflozin 25 mg, 10 mg, 5 mg, and 2.5 mg
Period Title: Overall Study
Started 219 [1] 218 [1] 219 [1] 220 [1] 107 [1]
Completed 205 205 202 201 103
Not Completed 14 13 17 19 4
Reason Not Completed
Adverse Event             5             5             4             13             1
Lack of Efficacy             0             0             0             0             1
Non compliant with Protocol             1             0             3             2             1
Lost to Follow-up             1             1             4             3             0
Patient withdrawal (not due to AE)             3             6             4             1             1
For other reason             4             1             2             0             0
[1]
randomised
Arm/Group Title Empa 12.5mg BID Empa 25mg QD Empa 5mg BID Empa 10mg QD Placebo Total
Hide Arm/Group Description Oral administration of Empagliflozin (Empa) 12.5 mg twice daily (BID) Oral administration of Empagliflozin (Empa) 25 mg once daily (QD) Oral administration of Empagliflozin (Empa) 5 mg twice daily (BID) Oral administration of Empagliflozin (Empa) 10 mg once daily (QD) Oral administration of Placebo tablets matching empagliflozin 25 mg, 10 mg, 5 mg, and 2.5 mg Total of all reporting groups
Overall Number of Baseline Participants 215 214 215 214 107 965
Hide Baseline Analysis Population Description
Full Analysis Set: FAS being defined as all patients randomised, treated with at least one dose of study drug, had a baseline Glycosylated Haemoglobin (HbA1c) and at least one on-treatment HbA1c assessment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 215 participants 214 participants 215 participants 214 participants 107 participants 965 participants
57.6  (9.9) 58.2  (10.2) 58.8  (9.8) 58.5  (10.8) 57.9  (11.2) 58.2  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 215 participants 214 participants 215 participants 214 participants 107 participants 965 participants
Female
92
  42.8%
100
  46.7%
95
  44.2%
106
  49.5%
52
  48.6%
445
  46.1%
Male
123
  57.2%
114
  53.3%
120
  55.8%
108
  50.5%
55
  51.4%
520
  53.9%
1.Primary Outcome
Title HbA1c (Glycosylated Haemoglobin) Change From Baseline at Week 16
Hide Description

Change from baseline in HbA1c (%) after 16 weeks of treatment. The term 'baseline' refers to the last observation prior to the first intake of any randomised study medication.

Means provided are the adjusted means.

Time Frame Baseline and 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Full Analysis Set (FAS) is the basis for the intention-to-treat analysis. FAS with last observation carried forward (LOCF) imputation is used as the primary method of accounting for missing data.

Values after the patient started rescue medication were excluded from analysis (and imputed with an LOCF procedure).

Arm/Group Title Empa 12.5mg BID Empa 25mg QD Empa 5mg BID Empa 10mg QD Placebo
Hide Arm/Group Description:
Oral administration of Empagliflozin (Empa) 12.5 mg twice daily (BID)
Oral administration of Empagliflozin (Empa) 25 mg once daily (QD)
Oral administration of Empagliflozin (Empa) 5 mg twice daily (BID)
Oral administration of Empagliflozin (Empa) 10 mg once daily (QD)
Oral administration of Placebo tablets matching empagliflozin 25 mg, 10 mg, 5 mg, and 2.5 mg
Overall Number of Participants Analyzed 215 214 215 213 107
Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-0.83  (0.05) -0.72  (0.05) -0.66  (0.05) -0.64  (0.05) -0.22  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 5mg BID, Empa 10mg QD
Comments The primary objective was to test the non-inferiority of empagliflozin 5 mg BID versus empagliflozin 10 mg QD, and non-inferiority of empagliflozin 12.5 mg BID versus empagliflozin 25 mg QD, assuming a non-inferiority margin of 0.35%
Type of Statistical Test Non-Inferiority or Equivalence
Comments

Null hypotheses for non-inferiority:

H10: Mean change from baseline in HbA1c (%) after 16 weeks of treatment with empagliflozin 5 mg twice daily ≥ mean change from baseline in HbA1c (%) after 16 weeks of treatment with empagliflozin 10 mg once daily + 0.35%

H20: Mean change from baseline in HbA1c (%) after 16 weeks of treatment with empagliflozin 12.5 mg twice daily ≥ mean change from baseline in HbA1c (%) after 16 weeks of treatment with empagliflozin 25 mg once daily + 0. 35%

Statistical Test of Hypothesis P-Value <0.0001
Comments The two non-inferiority hypotheses H10 and H20 were tested using the Hochberg procedure in order to control the family-wise type I error at 0.025 (one-sided).
Method ANCOVA
Comments ANCOVA: Treatment, geographical region, renal function (screening eGFR [MDRD] value)- fixed effects and baseline HbA1c- linear covariate.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.02
Confidence Interval 95%
-0.16 to 0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.07
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg BID, Empa 25mg QD
Comments The primary objective was to test the non-inferiority of empagliflozin 5 mg BID versus empagliflozin 10 mg QD, and non-inferiority of empagliflozin 12.5 mg BID versus empagliflozin 25 mg QD, assuming a non-inferiority margin of 0.35%
Type of Statistical Test Non-Inferiority or Equivalence
Comments

Null hypotheses for non-inferiority:

H10: Mean change from baseline in HbA1c (%) after 16 weeks of treatment with empagliflozin 5 mg twice daily ≥ mean change from baseline in HbA1c (%) after 16 weeks of treatment with empagliflozin 10 mg once daily + 0.35%

H20: Mean change from baseline in HbA1c (%) after 16 weeks of treatment with empagliflozin 12.5 mg twice daily ≥ mean change from baseline in HbA1c (%) after 16 weeks of treatment with empagliflozin 25 mg once daily + 0. 35%

Statistical Test of Hypothesis P-Value <0.0001
Comments The two non-inferiority hypotheses H10 and H20 were tested using the Hochberg procedure in order to control the family-wise type I error at 0.025 (one-sided).
Method ANCOVA
Comments ANCOVA: Treatment, geographical region, renal function (screening eGFR [MDRD] value)- fixed effects and baseline HbA1c- linear covariate.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.11
Confidence Interval 95%
-0.26 to 0.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.07
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg BID, Placebo
Comments Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing HbA1c after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA: Treatment, geographical region, renal function (screening eGFR [MDRD] value)- fixed effects and baseline HbA1c- linear covariate.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.61
Confidence Interval 95%
-0.79 to -0.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Empa 25mg QD, Placebo
Comments Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing HbA1c after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA: Treatment, geographical region, renal function (screening eGFR [MDRD] value)- fixed effects and baseline HbA1c- linear covariate.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.50
Confidence Interval 95%
-0.68 to -0.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Empa 5mg BID, Placebo
Comments Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing HbA1c after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA: Treatment, geographical region, renal function (screening eGFR [MDRD] value)- fixed effects and baseline HbA1c- linear covariate.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.44
Confidence Interval 95%
-0.62 to -0.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Empa 10mg QD, Placebo
Comments Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing HbA1c after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA: Treatment, geographical region, renal function (screening eGFR [MDRD] value)- fixed effects and baseline HbA1c- linear covariate.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -0.42
Confidence Interval 95%
-0.60 to -0.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Fasting Plasma Glucose (FPG) Change From Baseline at Week 16
Hide Description

Change from baseline in FPG (mg/dL) after 16 weeks of treatment. The term 'baseline' refers to the last observation prior to the first intake of any randomised study medication.

Means provided are the adjusted means.

Time Frame Baseline and 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS with LOCF has been used for FPG analyses
Arm/Group Title Empa 12.5mg BID Empa 25mg QD Empa 5mg BID Empa 10mg QD Placebo
Hide Arm/Group Description:
Oral administration of Empagliflozin (Empa) 12.5 mg twice daily (BID)
Oral administration of Empagliflozin (Empa) 25 mg once daily (QD)
Oral administration of Empagliflozin (Empa) 5 mg twice daily (BID)
Oral administration of Empagliflozin (Empa) 10 mg once daily (QD)
Oral administration of Placebo tablets matching empagliflozin 25 mg, 10 mg, 5 mg, and 2.5 mg
Overall Number of Participants Analyzed 213 214 213 213 107
Mean (Standard Error)
Unit of Measure: mg/dL
-27.7  (2.0) -22.7  (2.0) -21.2  (2.0) -17.6  (2.0) -0.2  (2.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 5mg BID, Empa 10mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA: Treatment, geographical region, renal function (screening (eGFR)[MDRD]value)-fixed effects and baseline HbA1c,baseline FPG-linear covariates
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -3.6
Confidence Interval 95%
-9.0 to 1.8
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg BID, Empa 25mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments The two non-inferiority hypotheses H10 and H20 were tested using the Hochberg procedure in order to control the family-wise type I error at 0.025 (one-sided).
Method ANCOVA
Comments ANCOVA: Treatment, geographical region, renal function (screening (eGFR)[MDRD]value)-fixed effects and baseline HbA1c,baseline FPG-linear covariates
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -5.0
Confidence Interval 95%
-10.4 to 0.5
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.8
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Empa 12.5mg BID, Placebo
Comments Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing FPG after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA:'Treatment','geographical region','renal function'(screening(eGFR)[MDRD]value)-fixed effects and 'baseline HbA1c',baseline FPG-linear covariate
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -27.5
Confidence Interval 95%
-34.2 to -20.9
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Empa 25mg QD, Placebo
Comments Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing FPG after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA:'Treatment','geographical region','renal function'(screening(eGFR)[MDRD]value)-fixed effects and 'baseline HbA1c',baseline FPG-linear covariate
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -22.5
Confidence Interval 95%
-29.2 to -15.9
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Empa 5mg BID, Placebo
Comments Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing FPG after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA:'Treatment','geographical region','renal function'(screening(eGFR)[MDRD]value)-fixed effects and 'baseline HbA1c',baseline FPG-linear covariate
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -21.1
Confidence Interval 95%
-27.7 to -14.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Empa 10mg QD, Placebo
Comments Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing FPG after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA:'Treatment','geographical region','renal function'(screening(eGFR)[MDRD]value)-fixed effects and 'baseline HbA1c',baseline FPG-linear covariate
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -17.5
Confidence Interval 95%
-24.1 to -10.8
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.4
Estimation Comments [Not Specified]
Time Frame 16 weeks + 1 week follow-up
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Empa 12.5mg BID Empa 25mg QD Empa 5mg BID Empa 10mg QD Placebo
Hide Arm/Group Description Oral administration of Empagliflozin (Empa) 12.5 mg twice daily (BID) Oral administration of Empagliflozin (Empa) 25 mg once daily (QD) Oral administration of Empagliflozin (Empa) 5 mg twice daily (BID) Oral administration of Empagliflozin (Empa) 10 mg once daily (QD) Oral administration of Placebo tablets matching empagliflozin 25 mg, 10 mg, 5 mg, and 2.5 mg
All-Cause Mortality
Empa 12.5mg BID Empa 25mg QD Empa 5mg BID Empa 10mg QD Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Empa 12.5mg BID Empa 25mg QD Empa 5mg BID Empa 10mg QD Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/219 (2.28%)   2/218 (0.92%)   7/219 (3.20%)   5/220 (2.27%)   1/107 (0.93%) 
Eye disorders           
Macular degeneration  1  0/219 (0.00%)  1/218 (0.46%)  0/219 (0.00%)  0/220 (0.00%)  0/107 (0.00%) 
Gastrointestinal disorders           
Inguinal hernia  1  0/219 (0.00%)  0/218 (0.00%)  0/219 (0.00%)  1/220 (0.45%)  0/107 (0.00%) 
Pancreatitis acute  1  0/219 (0.00%)  0/218 (0.00%)  1/219 (0.46%)  1/220 (0.45%)  0/107 (0.00%) 
Parotid gland enlargement  1  1/219 (0.46%)  0/218 (0.00%)  0/219 (0.00%)  0/220 (0.00%)  0/107 (0.00%) 
Rectal haemorrhage  1  1/219 (0.46%)  0/218 (0.00%)  0/219 (0.00%)  0/220 (0.00%)  0/107 (0.00%) 
Salivary gland pain  1  1/219 (0.46%)  0/218 (0.00%)  0/219 (0.00%)  0/220 (0.00%)  0/107 (0.00%) 
Hepatobiliary disorders           
Bile duct stone  1  0/219 (0.00%)  0/218 (0.00%)  0/219 (0.00%)  1/220 (0.45%)  0/107 (0.00%) 
Cholangitis  1  0/219 (0.00%)  0/218 (0.00%)  1/219 (0.46%)  0/220 (0.00%)  0/107 (0.00%) 
Cholecystitis acute  1  0/219 (0.00%)  0/218 (0.00%)  0/219 (0.00%)  1/220 (0.45%)  0/107 (0.00%) 
Cholelithiasis  1  0/219 (0.00%)  0/218 (0.00%)  1/219 (0.46%)  0/220 (0.00%)  0/107 (0.00%) 
Infections and infestations           
Diverticulitis  1  0/219 (0.00%)  1/218 (0.46%)  0/219 (0.00%)  0/220 (0.00%)  0/107 (0.00%) 
Pharyngotonsillitis  1  0/219 (0.00%)  0/218 (0.00%)  1/219 (0.46%)  0/220 (0.00%)  0/107 (0.00%) 
Musculoskeletal and connective tissue disorders           
Exostosis of jaw  1  0/219 (0.00%)  0/218 (0.00%)  1/219 (0.46%)  0/220 (0.00%)  0/107 (0.00%) 
Spinal osteoarthritis  1  0/219 (0.00%)  0/218 (0.00%)  0/219 (0.00%)  1/220 (0.45%)  0/107 (0.00%) 
Synovial cyst  1  0/219 (0.00%)  0/218 (0.00%)  1/219 (0.46%)  0/220 (0.00%)  0/107 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Biliary adenoma  1  0/219 (0.00%)  0/218 (0.00%)  0/219 (0.00%)  1/220 (0.45%)  0/107 (0.00%) 
Bladder transitional cell carcinoma  1  0/219 (0.00%)  0/218 (0.00%)  0/219 (0.00%)  1/220 (0.45%)  0/107 (0.00%) 
Prostate cancer  1  0/219 (0.00%)  0/218 (0.00%)  1/219 (0.46%)  0/220 (0.00%)  0/107 (0.00%) 
Squamous cell carcinoma  1  1/219 (0.46%)  0/218 (0.00%)  0/219 (0.00%)  0/220 (0.00%)  0/107 (0.00%) 
Nervous system disorders           
Cerebrovascular accident  1  0/219 (0.00%)  0/218 (0.00%)  0/219 (0.00%)  0/220 (0.00%)  1/107 (0.93%) 
Ischaemic stroke  1  1/219 (0.46%)  0/218 (0.00%)  0/219 (0.00%)  0/220 (0.00%)  0/107 (0.00%) 
Transient ischaemic attack  1  1/219 (0.46%)  0/218 (0.00%)  0/219 (0.00%)  0/220 (0.00%)  0/107 (0.00%) 
Renal and urinary disorders           
Urinary incontinence  1  0/219 (0.00%)  0/218 (0.00%)  1/219 (0.46%)  0/220 (0.00%)  0/107 (0.00%) 
Skin and subcutaneous tissue disorders           
Psoriasis  1  1/219 (0.46%)  0/218 (0.00%)  0/219 (0.00%)  0/220 (0.00%)  0/107 (0.00%) 
Vascular disorders           
Hypertensive crisis  1  0/219 (0.00%)  0/218 (0.00%)  1/219 (0.46%)  0/220 (0.00%)  0/107 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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 BID Empa 25mg QD Empa 5mg BID Empa 10mg QD Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/219 (4.57%)   10/218 (4.59%)   8/219 (3.65%)   15/220 (6.82%)   4/107 (3.74%) 
Infections and infestations           
Urinary tract infection  1  10/219 (4.57%)  10/218 (4.59%)  8/219 (3.65%)  15/220 (6.82%)  4/107 (3.74%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01649297     History of Changes
Other Study ID Numbers: 1276.10
2012-000905-53 ( EudraCT Number: EudraCT )
First Submitted: July 23, 2012
First Posted: July 25, 2012
Results First Submitted: June 26, 2015
Results First Posted: July 23, 2015
Last Update Posted: July 23, 2015