Efficacy and Safety of Empagliflozin (BI 10773) in Patients With Type 2 Diabetes and Renal Impairment
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT01164501
Collaborator
Eli Lilly and Company (Industry)
741
127
3
24
5.8
0.2
Study Details
Study Description
Brief Summary
This study will investigate the efficacy and safety of the BI 10773 in type 2 diabetic patients with renal impairment in order to provide these data for approval for BI 10773 as an antidiabetic agent by regulatory authorities.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
741 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Primary Purpose:
Treatment
Official Title:
A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of BI 10773 (10 mg and 25 mg Administered Once Daily) as Add on to Pre-existing Antidiabetic Therapy Over 52 Weeks in Patients With Type 2 Diabetes Mellitus and Renal Impairment and Insufficient Glycaemic Control
Study Start Date
:
Jul 1, 2010
Actual Primary Completion Date
:
Jul 1, 2012
Actual Study Completion Date
:
Jul 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BI 10773 low dose BI 10773 tablets once daily |
Drug: BI 10773
BI 10773 tablets once daily
Drug: Placebo
Placebo tablets identical to BI 10773 high dose
|
| Experimental: BI 10773 high dose BI 10773 tablets once daily |
Drug: Placebo
Placebo tablets identical to BI 10773 low dose
Drug: BI 10773
BI 10773 tablets once daily
|
| Placebo Comparator: Placebo Placebo tablets matching BI 10773 |
Drug: Placebo
Placebo tablets identical to BI 10773 high dose
Drug: Placebo
Placebo tablets identical to BI 10773 low dose
|
Outcome Measures
Primary Outcome Measures
- HbA1c Change From Baseline in Patients With Mild or Moderate Renal Impairment [Baseline and 24 weeks]
Change from baseline in HbA1c after 24 weeks, for patients with mild or moderate renal impairment. Note adjusted means are provided.
- HbA1c Change From Baseline in Patients With Mild Renal Impairment [Baseline and 24 weeks]
Change from baseline in HbA1c after 24 weeks, for patients with mild renal impairment. Note adjusted means are provided.
- HbA1c Change From Baseline in Patients With Moderate Renal Impairment [Baseline and 24 weeks]
Change from baseline in HbA1c after 24 weeks, for patients with moderate renal impairment. Note adjusted means are provided.
Other Outcome Measures
- Hypoglycaemic Events [From first drug administration until 7 days after last trial medication intake, up to 458 days]
Percentage of patients who experienced a hypoglycaemic event. A hypoglycaemic event was regarded as confirmed if it was documented as an adverse event with plasma glucose values <= 70 mg/dL (<=3.9mmol/L) measured or with a documentation that the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative action had been required.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
-
Diagnosis of type 2 diabetes mellitus prior to informed consent and an estimated glomerular filtration rate of <90 ml/min.
-
Male and female patients on diet and exercise regimen who are pre-treated with any antidiabetic therapy and are on the maximum tolerated dose which has been unchanged for 12 weeks prior to randomisation.
-
HbA1c greater than or equal to 7.0% and less than or equal to 10.0% .
-
Aged 18 years or above.
-
Body Mass Index less than or equal to 45 kg/m2
Exclusion criteria:
-
Uncontrolled hyperglycaemia defined as >13.3 mmol/L after an overnight fast during placebo run-in.
-
Impaired renal function, defined as an estimated glomerular filtration rate <15 ml/min.
-
Renal impairment requiring any form of chronic dialysis.
-
Requiring acute dialysis within three months prior to informed consent.
-
Renal transplant recipient.
-
Myocardial infarction, stroke or Transient Ischemic Attack within three months prior to informed consent.
-
Indication of liver disease.
-
Bariatric surgery within the past two years.
-
Medical history of cancer.
-
Blood dyscrasias or any disorders causing hemolysis or unstable red blood cell.
-
Contraindications to pre-existing background antidiabetic therapy.
-
Treatment with anti-obesity drugs.
-
Current treatment with systemic steroids or change in dosage of thyroid hormones within six weeks prior to informed consent or any other uncontrolled endocrine disorder except Type 2 Diabetes.
-
Pre-menopausal women who are nursing or pregnant or are of child-bearing potential and are not practising an acceptable method of birth control.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1245.36.10014 Boehringer Ingelheim Investigational Site | Anaheim | California | United States | |
| 2 | 1245.36.10019 Boehringer Ingelheim Investigational Site | Lomita | California | United States | |
| 3 | 1245.36.10017 Boehringer Ingelheim Investigational Site | Plantation | Florida | United States | |
| 4 | 1245.36.10009 Boehringer Ingelheim Investigational Site | West Palm Beach | Florida | United States | |
| 5 | 1245.36.10018 Boehringer Ingelheim Investigational Site | Honolulu | Hawaii | United States | |
| 6 | 1245.36.10015 Boehringer Ingelheim Investigational Site | Shreveport | Louisiana | United States | |
| 7 | 1245.36.10021 Boehringer Ingelheim Investigational Site | Endwell | New York | United States | |
| 8 | 1245.36.10008 Boehringer Ingelheim Investigational Site | Greenville | North Carolina | United States | |
| 9 | 1245.36.10005 Boehringer Ingelheim Investigational Site | Bethlehem | Pennsylvania | United States | |
| 10 | 1245.36.10003 Boehringer Ingelheim Investigational Site | Melrose Park | Pennsylvania | United States | |
| 11 | 1245.36.10004 Boehringer Ingelheim Investigational Site | Greer | South Carolina | United States | |
| 12 | 1245.36.10012 Boehringer Ingelheim Investigational Site | Corpus Christi | Texas | United States | |
| 13 | 1245.36.10013 Boehringer Ingelheim Investigational Site | Dallas | Texas | United States | |
| 14 | 1245.36.10002 Boehringer Ingelheim Investigational Site | Houston | Texas | United States | |
| 15 | 1245.36.10007 Boehringer Ingelheim Investigational Site | San Antonio | Texas | United States | |
| 16 | 1245.36.10023 Boehringer Ingelheim Investigational Site | Renton | Washington | United States | |
| 17 | 1245.36.10011 Boehringer Ingelheim Investigational Site | Spokane | Washington | United States | |
| 18 | 1245.36.10006 Boehringer Ingelheim Investigational Site | Tacoma | Washington | United States | |
| 19 | 1245.36.20052 Boehringer Ingelheim Investigational Site | Calgary | Alberta | Canada | |
| 20 | 1245.36.20054 Boehringer Ingelheim Investigational Site | Calgary | Alberta | Canada | |
| 21 | 1245.36.20023 Boehringer Ingelheim Investigational Site | Edmonton | Alberta | Canada | |
| 22 | 1245.36.20055 Boehringer Ingelheim Investigational Site | Edmonton | Alberta | Canada | |
| 23 | 1245.36.20048 Boehringer Ingelheim Investigational Site | Winnipeg | Manitoba | Canada | |
| 24 | 1245.36.20051 Boehringer Ingelheim Investigational Site | Mississauga | Ontario | Canada | |
| 25 | 1245.36.20086 Boehringer Ingelheim Investigational Site | Thornhill | Ontario | Canada | |
| 26 | 1245.36.20053 Boehringer Ingelheim Investigational Site | Toronto | Ontario | Canada | |
| 27 | 1245.36.20056 Boehringer Ingelheim Investigational Site | Montreal | Quebec | Canada | |
| 28 | 1245.36.33001 Boehringer Ingelheim Investigational Site | Corbeil Essonnes | France | ||
| 29 | 1245.36.33042 Boehringer Ingelheim Investigational Site | Nanterre Cedex | France | ||
| 30 | 1245.36.33041 Boehringer Ingelheim Investigational Site | Nice | France | ||
| 31 | 1245.36.33036 Boehringer Ingelheim Investigational Site | Paris | France | ||
| 32 | 1245.36.33040 Boehringer Ingelheim Investigational Site | Poitiers | France | ||
| 33 | 1245.36.33038 Boehringer Ingelheim Investigational Site | Reims Cedex | France | ||
| 34 | 1245.36.33037 Boehringer Ingelheim Investigational Site | Reims | France | ||
| 35 | 1245.36.33043 Boehringer Ingelheim Investigational Site | Rennes | France | ||
| 36 | 1245.36.33044 Boehringer Ingelheim Investigational Site | Saint Mandé | France | ||
| 37 | 1245.36.85201 Boehringer Ingelheim Investigational Site | Hong Kong | Hong Kong | ||
| 38 | 1245.36.85204 Boehringer Ingelheim Investigational Site | Hong Kong | Hong Kong | ||
| 39 | 1245.36.85205 Boehringer Ingelheim Investigational Site | Hong Kong | Hong Kong | ||
| 40 | 1245.36.85206 Boehringer Ingelheim Investigational Site | Hong Kong | Hong Kong | ||
| 41 | 1245.36.85202 Boehringer Ingelheim Investigational Site | Kowloon | Hong Kong | ||
| 42 | 1245.36.91209 Boehringer Ingelheim Investigational Site | Aligarh, Uttar Pradesh | India | ||
| 43 | 1245.36.91202 Boehringer Ingelheim Investigational Site | Bangalore | India | ||
| 44 | 1245.36.91204 Boehringer Ingelheim Investigational Site | Bangalore | India | ||
| 45 | 1245.36.91205 Boehringer Ingelheim Investigational Site | Bangalore | India | ||
| 46 | 1245.36.91208 Boehringer Ingelheim Investigational Site | Bangalore | India | ||
| 47 | 1245.36.91201 Boehringer Ingelheim Investigational Site | Chennai | India | ||
| 48 | 1245.36.91214 Boehringer Ingelheim Investigational Site | Chennai | India | ||
| 49 | 1245.36.91213 Boehringer Ingelheim Investigational Site | Gurgaon | India | ||
| 50 | 1245.36.91203 Boehringer Ingelheim Investigational Site | Hyderabad | India | ||
| 51 | 1245.36.91211 Boehringer Ingelheim Investigational Site | Kolkata | India | ||
| 52 | 1245.36.91210 Boehringer Ingelheim Investigational Site | Mangalore | India | ||
| 53 | 1245.36.91215 Boehringer Ingelheim Investigational Site | Mumbai, Maharastra | India | ||
| 54 | 1245.36.91216 Boehringer Ingelheim Investigational Site | Nasik | India | ||
| 55 | 1245.36.91212 Boehringer Ingelheim Investigational Site | New Delhi | India | ||
| 56 | 1245.36.91207 Boehringer Ingelheim Investigational Site | Pune | India | ||
| 57 | 1245.36.60003 Boehringer Ingelheim Investigational Site | Johor Baru | Malaysia | ||
| 58 | 1245.36.60006 Boehringer Ingelheim Investigational Site | Kelantan Kota Bahru | Malaysia | ||
| 59 | 1245.36.60005 Boehringer Ingelheim Investigational Site | Kuala Lumpur | Malaysia | ||
| 60 | 1245.36.60009 Boehringer Ingelheim Investigational Site | Kuala Lumpur | Malaysia | ||
| 61 | 1245.36.60004 Boehringer Ingelheim Investigational Site | Pahang | Malaysia | ||
| 62 | 1245.36.60007 Boehringer Ingelheim Investigational Site | Perak | Malaysia | ||
| 63 | 1245.36.60011 Boehringer Ingelheim Investigational Site | Perak | Malaysia | ||
| 64 | 1245.36.60010 Boehringer Ingelheim Investigational Site | Pulau Piang | Malaysia | ||
| 65 | 1245.36.60008 Boehringer Ingelheim Investigational Site | Sabah | Malaysia | ||
| 66 | 1245.36.60001 Boehringer Ingelheim Investigational Site | Selangor Darul Ehsan | Malaysia | ||
| 67 | 1245.36.31015 Boehringer Ingelheim Investigational Site | Amersfoort | Netherlands | ||
| 68 | 1245.36.31004 Boehringer Ingelheim Investigational Site | Den Haag | Netherlands | ||
| 69 | 1245.36.31012 Boehringer Ingelheim Investigational Site | Geleen | Netherlands | ||
| 70 | 1245.36.31017 Boehringer Ingelheim Investigational Site | Hardenberg | Netherlands | ||
| 71 | 1245.36.31009 Boehringer Ingelheim Investigational Site | Maastricht | Netherlands | ||
| 72 | 1245.36.31002 Boehringer Ingelheim Investigational Site | Utrecht | Netherlands | ||
| 73 | 1245.36.31003 Boehringer Ingelheim Investigational Site | Zaandam | Netherlands | ||
| 74 | 1245.36.63008 Boehringer Ingelheim Investigational Site | Cavite City | Philippines | ||
| 75 | 1245.36.63006 Boehringer Ingelheim Investigational Site | Cebu | Philippines | ||
| 76 | 1245.36.63005 Boehringer Ingelheim Investigational Site | Manila | Philippines | ||
| 77 | 1245.36.63007 Boehringer Ingelheim Investigational Site | Manila | Philippines | ||
| 78 | 1245.36.63009 Boehringer Ingelheim Investigational Site | Marikina | Philippines | ||
| 79 | 1245.36.63010 Boehringer Ingelheim Investigational Site | Tacloban | Philippines | ||
| 80 | 1245.36.48006 Boehringer Ingelheim Investigational Site | Gdansk | Poland | ||
| 81 | 1245.36.48003 Boehringer Ingelheim Investigational Site | Lodz | Poland | ||
| 82 | 1245.36.48004 Boehringer Ingelheim Investigational Site | Lodz | Poland | ||
| 83 | 1245.36.48001 Boehringer Ingelheim Investigational Site | Lublin | Poland | ||
| 84 | 1245.36.48002 Boehringer Ingelheim Investigational Site | Poznan | Poland | ||
| 85 | 1245.36.48007 Boehringer Ingelheim Investigational Site | Ruda Slaska | Poland | ||
| 86 | 1245.36.48005 Boehringer Ingelheim Investigational Site | Torun | Poland | ||
| 87 | 1245.36.35003 Boehringer Ingelheim Investigational Site | Faro | Portugal | ||
| 88 | 1245.36.35002 Boehringer Ingelheim Investigational Site | Lisboa | Portugal | ||
| 89 | 1245.36.35004 Boehringer Ingelheim Investigational Site | Lisboa | Portugal | ||
| 90 | 1245.36.35001 Boehringer Ingelheim Investigational Site | Vila Nova de Gaia | Portugal | ||
| 91 | 1245.36.70008 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 92 | 1245.36.70009 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 93 | 1245.36.70011 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 94 | 1245.36.70004 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 95 | 1245.36.70006 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 96 | 1245.36.70002 Boehringer Ingelheim Investigational Site | Vsevolozhsk | Russian Federation | ||
| 97 | 1245.36.74011 Boehringer Ingelheim Investigational Site | Moldava nad Bodvou | Slovakia | ||
| 98 | 1245.36.74013 Boehringer Ingelheim Investigational Site | Nitra | Slovakia | ||
| 99 | 1245.36.74008 Boehringer Ingelheim Investigational Site | Nove Mesto Nad Vahom | Slovakia | ||
| 100 | 1245.36.74012 Boehringer Ingelheim Investigational Site | Presov | Slovakia | ||
| 101 | 1245.36.74007 Boehringer Ingelheim Investigational Site | Trencin | Slovakia | ||
| 102 | 1245.36.74009 Boehringer Ingelheim Investigational Site | Zilina | Slovakia | ||
| 103 | 1245.36.76021 Boehringer Ingelheim Investigational Site | Plumstead | South Africa | ||
| 104 | 1245.36.76020 Boehringer Ingelheim Investigational Site | Somerset West | South Africa | ||
| 105 | 1245.36.76022 Boehringer Ingelheim Investigational Site | Somerset West | South Africa | ||
| 106 | 1245.36.34015 Boehringer Ingelheim Investigational Site | Barcelona | Spain | ||
| 107 | 1245.36.34009 Boehringer Ingelheim Investigational Site | Granada | Spain | ||
| 108 | 1245.36.34014 Boehringer Ingelheim Investigational Site | L'Hospitalet de Llobregat | Spain | ||
| 109 | 1245.36.34012 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 110 | 1245.36.34013 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 111 | 1245.36.34020 Boehringer Ingelheim Investigational Site | Manresa | Spain | ||
| 112 | 1245.36.34021 Boehringer Ingelheim Investigational Site | San Sebastian de los Reyes | Spain | ||
| 113 | 1245.36.34016 Boehringer Ingelheim Investigational Site | Santiago de Compostela | Spain | ||
| 114 | 1245.36.34017 Boehringer Ingelheim Investigational Site | Valencia | Spain | ||
| 115 | 1245.36.34019 Boehringer Ingelheim Investigational Site | Valencia | Spain | ||
| 116 | 1245.36.44018 Boehringer Ingelheim Investigational Site | Bath | United Kingdom | ||
| 117 | 1245.36.44010 Boehringer Ingelheim Investigational Site | Birmingham | United Kingdom | ||
| 118 | 1245.36.44013 Boehringer Ingelheim Investigational Site | Blackpool | United Kingdom | ||
| 119 | 1245.36.44016 Boehringer Ingelheim Investigational Site | Blackpool | United Kingdom | ||
| 120 | 1245.36.44012 Boehringer Ingelheim Investigational Site | Chesterfield | United Kingdom | ||
| 121 | 1245.36.44026 Boehringer Ingelheim Investigational Site | Chester | United Kingdom | ||
| 122 | 1245.36.44025 Boehringer Ingelheim Investigational Site | Doncaster | United Kingdom | ||
| 123 | 1245.36.44036 Boehringer Ingelheim Investigational Site | Epsom | United Kingdom | ||
| 124 | 1245.36.44001 Boehringer Ingelheim Investigational Site | Frome | United Kingdom | ||
| 125 | 1245.36.44007 Boehringer Ingelheim Investigational Site | Midsomer Norton | United Kingdom | ||
| 126 | 1245.36.44023 Boehringer Ingelheim Investigational Site | Nantwich | United Kingdom | ||
| 127 | 1245.36.44024 Boehringer Ingelheim Investigational Site | Welwyn Garden City | United Kingdom |
Sponsors and Collaborators
- Boehringer Ingelheim
- Eli Lilly and Company
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01164501
Other Study ID Numbers:
- 1245.36
- 2009-016179-31
First Posted:
Jul 16, 2010
Last Update Posted:
Jun 16, 2014
Last Verified:
May 1, 2014
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | Empa 10mg | Empa 25mg |
|---|---|---|---|
| Arm/Group Description | Placebo tablets, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 10mg plus a placebo tablet matching the 25mg empa dose were taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 25mg plus a placebo tablet matching the 10mg empa dose were taken once daily for 52 weeks. |
| Period Title: Overall Study | |||
| STARTED | 321 | 98 | 322 |
| COMPLETED | 278 | 88 | 280 |
| NOT COMPLETED | 43 | 10 | 42 |
Baseline Characteristics
| Arm/Group Title | Placebo | Empa 10mg | Empa 25mg | Total |
|---|---|---|---|---|
| Arm/Group Description | Placebo tablets, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 10mg plus a placebo tablet matching the 25mg empa dose were taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 25mg plus a placebo tablet matching the 10mg empa dose were taken once daily for 52 weeks. | Total of all reporting groups |
| Overall Participants | 319 | 98 | 321 | 738 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
64.1
(8.7)
|
63.2
(8.5)
|
63.9
(9.0)
|
63.9
(8.8)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
138
43.3%
|
38
38.8%
|
132
41.1%
|
308
41.7%
|
| Male |
181
56.7%
|
60
61.2%
|
189
58.9%
|
430
58.3%
|
Outcome Measures
| Title | HbA1c Change From Baseline in Patients With Mild or Moderate Renal Impairment |
|---|---|
| Description | Change from baseline in HbA1c after 24 weeks, for patients with mild or moderate renal impairment. Note adjusted means are provided. |
| Time Frame | Baseline and 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) which included all randomised patients, treated with at least one dose of trial medication, who had a baseline HbA1c value. 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 25mg |
|---|---|---|
| Arm/Group Description | Placebo tablets, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 25mg plus a placebo tablet matching the 10mg empa dose were taken once daily for 52 weeks. |
| Measure Participants | 282 | 284 |
| Mean (Standard Error) [percentage of HbA1c] |
0.05
(0.04)
|
-0.46
(0.04)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Empa 25mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hierarchical testing to adjust for multiple comparisons, no adjustment in p-values. Empa 25 mg versus placebo in mild or moderate renal impaired patients was the first step in the hierarchical sequence. | |
| Method | ANCOVA | |
| Comments | Based on ANCOVA with terms for treatment, background antidiabetic medication, renal impairment and baseline HbA1c. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.51 | |
| Confidence Interval |
(2-Sided) 95% -0.62 to -0.39 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.06 |
|
| Estimation Comments | Difference calculated as empa 25mg minus placebo | |
| Title | HbA1c Change From Baseline in Patients With Mild Renal Impairment |
|---|---|
| Description | Change from baseline in HbA1c after 24 weeks, for patients with mild renal impairment. Note adjusted means are provided. |
| Time Frame | Baseline and 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) which included all randomised patients, treated with at least one dose of trial medication, who had a baseline HbA1c value. 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 |
|---|---|---|---|
| Arm/Group Description | Placebo tablets, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 10mg plus a placebo tablet matching the 25mg empa dose were taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 25mg plus a placebo tablet matching the 10mg empa dose were taken once daily for 52 weeks. |
| Measure Participants | 95 | 98 | 97 |
| Mean (Standard Error) [percentage of HbA1c] |
0.06
(0.07)
|
-0.46
(0.07)
|
-0.63
(0.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Empa 25mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hierarchical testing to adjust for multiple comparisons, no adjustment in p-values. Empa 25 mg versus placebo in mild renal impaired patients was the second step in the hierarchical sequence. | |
| Method | ANCOVA | |
| Comments | Based on ANCOVA with terms for treatment, background antidiabetic medication and baseline HbA1c. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.52 | |
| Confidence Interval |
(2-Sided) 95% -0.72 to -0.32 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | Difference calculated as empa 10mg minus placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Empa 25mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hierarchical testing to adjust for multiple comparisons, no adjustment in p-values. Empa 10 mg versus placebo in mild renal impaired patients was the third step in the hierarchical sequence. | |
| Method | ANCOVA | |
| Comments | Based on ANCOVA with terms for treatment, background antidiabetic medication and baseline HbA1c. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.68 | |
| Confidence Interval |
(2-Sided) 95% -0.88 to -0.49 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | Difference calculated as empa 25mg minus placebo | |
| Title | HbA1c Change From Baseline in Patients With Moderate Renal Impairment |
|---|---|
| Description | Change from baseline in HbA1c after 24 weeks, for patients with moderate renal impairment. Note adjusted means are provided. |
| Time Frame | Baseline and 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) which included all randomised patients, treated with at least one dose of trial medication, who had a baseline HbA1c value. 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 25mg |
|---|---|---|
| Arm/Group Description | Placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 25mg plus a placebo tablet matching the 10mg empa dose were taken once daily for 52 weeks. |
| Measure Participants | 187 | 187 |
| Mean (Standard Error) [percentage of HbA1c] |
0.05
(0.05)
|
-0.37
(0.05)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Empa 25mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hierarchical testing to adjust for multiple comparisons, no adjustment in p-values. Empa 10 mg versus placebo in moderate renal impaired patients was the fourth step in the hierarchical sequence. | |
| Method | ANCOVA | |
| Comments | Based on ANCOVA with terms for treatment, background antidiabetic medication and baseline HbA1c. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.42 | |
| Confidence Interval |
(2-Sided) 95% -0.56 to -0.28 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.07 |
|
| Estimation Comments | Difference calculated as empa 25mg minus placebo | |
| Title | Hypoglycaemic Events |
|---|---|
| Description | Percentage of patients who experienced a hypoglycaemic event. A hypoglycaemic event was regarded as confirmed if it was documented as an adverse event with plasma glucose values <= 70 mg/dL (<=3.9mmol/L) measured or with a documentation that the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative action had been required. |
| Time Frame | From first drug administration until 7 days after last trial medication intake, up to 458 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set which included all patients treated with at least one dose of randomised trial medication. |
| Arm/Group Title | Placebo | Empa 10mg | Empa 25mg |
|---|---|---|---|
| Arm/Group Description | Placebo tablets, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 10mg plus a placebo tablet matching the 25mg empa dose were taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 25mg plus a placebo tablet matching the 10mg empa dose were taken once daily for 52 weeks. |
| Measure Participants | 319 | 98 | 321 |
| Number [percentage of participants] |
27.6
8.7%
|
26.5
27%
|
27.4
8.5%
|
Adverse Events
| Time Frame | From first drug administration until 7 days after last trial medication intake, up to 458 days | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Placebo | Empa 10mg | Empa 25mg | |||
| Arm/Group Description | Placebo tablets, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 10mg plus a placebo tablet matching the 25mg empa dose were taken once daily for 52 weeks. | Single oral dose of empagliflozin (empa) 25mg plus a placebo tablet matching the 10mg empa dose were taken once daily for 52 weeks. | |||
All Cause Mortality |
||||||
| Placebo | Empa 10mg | Empa 25mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Placebo | Empa 10mg | Empa 25mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 44/319 (13.8%) | 6/98 (6.1%) | 40/321 (12.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/319 (0.3%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Thrombocytopenia | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Cardiac disorders | ||||||
| Acute coronary syndrome | 0/319 (0%) | 1/98 (1%) | 0/321 (0%) | |||
| Acute myocardial infarction | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Angina unstable | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Arrhythmia | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Atrial fibrillation | 2/319 (0.6%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Atrioventricular block | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Cardiac arrest | 1/319 (0.3%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Cardiac failure | 3/319 (0.9%) | 0/98 (0%) | 0/321 (0%) | |||
| Cardiac failure congestive | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Cardiogenic shock | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Coronary artery occlusion | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Myocardial ischaemia | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Sick sinus syndrome | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Eye disorders | ||||||
| Cataract | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Glaucoma | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Retinal artery occlusion | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Abdominal pain upper | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Colonic polyp | 1/319 (0.3%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Constipation | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Diarrhoea | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Gastritis erosive | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Intestinal obstruction | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Oesophageal varices haemorrhage | 0/319 (0%) | 1/98 (1%) | 0/321 (0%) | |||
| Pancreatitis | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Pancreatitis acute | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| General disorders | ||||||
| Chest pain | 3/319 (0.9%) | 1/98 (1%) | 0/321 (0%) | |||
| Oedema peripheral | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Sudden cardiac death | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Cholecystitis acute | 0/319 (0%) | 1/98 (1%) | 0/321 (0%) | |||
| Cholelithiasis | 1/319 (0.3%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Hepatitis | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Infections and infestations | ||||||
| Bronchopneumonia | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Campylobacter gastroenteritis | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Cellulitis | 0/319 (0%) | 0/98 (0%) | 2/321 (0.6%) | |||
| Dengue fever | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Gangrene | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Pharyngitis | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Pneumonia | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Pneumonia primary atypical | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Post procedural infection | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Respiratory tract infection | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Sepsis | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Urinary tract infection | 2/319 (0.6%) | 0/98 (0%) | 3/321 (0.9%) | |||
| Injury, poisoning and procedural complications | ||||||
| Clavicle fracture | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Fall | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Humerus fracture | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Joint injury | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Limb injury | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Neck injury | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Pelvic fracture | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Pneumothorax traumatic | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Rib fracture | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Spinal fracture | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Subdural haematoma | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Traumatic lung injury | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Wound | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus inadequate control | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Diabetic ketoacidosis | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Fluid overload | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Hyperglycaemia | 0/319 (0%) | 0/98 (0%) | 2/321 (0.6%) | |||
| Hypoglycaemia | 0/319 (0%) | 0/98 (0%) | 3/321 (0.9%) | |||
| Hypovolaemia | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Metabolic disorder | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthritis | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Back pain | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Osteoarthritis | 0/319 (0%) | 1/98 (1%) | 1/321 (0.3%) | |||
| Pain in extremity | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Malignant melanoma | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Oesophageal carcinoma | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Oropharyngeal cancer stage unspecified | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Pancreatic carcinoma | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Prostate cancer metastatic | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Skin cancer | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Squamous cell carcinoma | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Squamous cell carcinoma of skin | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Nervous system disorders | ||||||
| Aphasia | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Cerebral infarction | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Cerebrovascular accident | 1/319 (0.3%) | 0/98 (0%) | 2/321 (0.6%) | |||
| Dizziness | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Dysarthria | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Embolic cerebral infarction | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Hypoaesthesia | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Hypoxic-ischaemic encephalopathy | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Lacunar infarction | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Syncope | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Transient ischaemic attack | 1/319 (0.3%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Psychiatric disorders | ||||||
| Abnormal behaviour | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Depressive symptom | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Renal and urinary disorders | ||||||
| Diabetic nephropathy | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Renal colic | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Renal failure | 1/319 (0.3%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Renal failure acute | 3/319 (0.9%) | 0/98 (0%) | 3/321 (0.9%) | |||
| Renal failure chronic | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Renal impairment | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Benign prostatic hyperplasia | 0/319 (0%) | 1/98 (1%) | 0/321 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Epistaxis | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Hypoxia | 1/319 (0.3%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Pharyngeal oedema | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Pulmonary embolism | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Pulmonary oedema | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Diabetic foot | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Vascular disorders | ||||||
| Aortic stenosis | 0/319 (0%) | 1/98 (1%) | 0/321 (0%) | |||
| Circulatory collapse | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Deep vein thrombosis | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Extremity necrosis | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Hypertension | 2/319 (0.6%) | 0/98 (0%) | 0/321 (0%) | |||
| Hypotension | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Intra-abdominal haematoma | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Lymphocele | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Peripheral ischaemia | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
| Subclavian artery stenosis | 1/319 (0.3%) | 0/98 (0%) | 0/321 (0%) | |||
| Thrombophlebitis | 0/319 (0%) | 0/98 (0%) | 1/321 (0.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Placebo | Empa 10mg | Empa 25mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 207/319 (64.9%) | 64/98 (65.3%) | 187/321 (58.3%) | |||
| Infections and infestations | ||||||
| Balanitis candida | 0/319 (0%) | 5/98 (5.1%) | 0/321 (0%) | |||
| Influenza | 8/319 (2.5%) | 6/98 (6.1%) | 8/321 (2.5%) | |||
| Nasopharyngitis | 29/319 (9.1%) | 6/98 (6.1%) | 27/321 (8.4%) | |||
| Upper respiratory tract infection | 25/319 (7.8%) | 14/98 (14.3%) | 35/321 (10.9%) | |||
| Urinary tract infection | 39/319 (12.2%) | 14/98 (14.3%) | 38/321 (11.8%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperglycaemia | 41/319 (12.9%) | 4/98 (4.1%) | 23/321 (7.2%) | |||
| Hypoglycaemia | 92/319 (28.8%) | 27/98 (27.6%) | 89/321 (27.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 21/319 (6.6%) | 7/98 (7.1%) | 13/321 (4%) | |||
| Back pain | 19/319 (6%) | 8/98 (8.2%) | 19/321 (5.9%) | |||
| Pain in extremity | 10/319 (3.1%) | 8/98 (8.2%) | 6/321 (1.9%) | |||
| Nervous system disorders | ||||||
| Headache | 13/319 (4.1%) | 5/98 (5.1%) | 16/321 (5%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 25/319 (7.8%) | 2/98 (2%) | 11/321 (3.4%) | |||
| Vascular disorders | ||||||
| Hypertension | 20/319 (6.3%) | 1/98 (1%) | 14/321 (4.4%) | |||
Limitations/Caveats
In this trial, only patients with mild or moderate renal impairment were analysed. Patients with severe or no renal impairment were not analysed.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01164501
Other Study ID Numbers:
- 1245.36
- 2009-016179-31
First Posted:
Jul 16, 2010
Last Update Posted:
Jun 16, 2014
Last Verified:
May 1, 2014