BI 10773 add-on to Metformin in Patients With Type 2 Diabetes

Phase 2

Completed

Conditions: Diabetes Mellitus, Type 2

Registration Number: NCT00749190

Lead Sponsor: Boehringer Ingelheim

Brief Summary: The objective of the current study is to investigate the efficacy, safety and pharmacokinetics of five doses of BI 10773 compared to placebo given for 12 weeks as add-on therapy to on going metformin therapy in patients with T2DM with insufficient glycemic control. In addition, there will be an open-label treatment arm with sitagliptin (JanuviaTM) as add-on therapy to metformin.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 495

Inclusion Criteria

Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone or with metformin and one other oral antidiabetic drug
Stable metformin therapy of at least 1500 mg/day, or less if that is a maximum tolerated dose.
HbA1c at screening 6.5% to 9.0% for patients on metformin and one other antidiabetic drug, and HbA1c >7.0% to 10% for patients on metformin only
HbA1c >7.0% to 10.0% at Visit 2 (Start of Run-in)
Age >=18 and <80years
Body Mass Index (BMI) <=40 kg/m2
Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion Criteria

Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent
Impaired hepatic function
Renal insufficiency or impaired renal function
Diseases of the central nervous system or psychiatric disorders or clinically relevant neurological disorders that may interfere with participation in the trial
Chronic or clinically relevant acute infections
Current or chronic urogenital tract infection
History of clinically relevant allergy/hypersensitivity
Treatment with glitazones (e.g., rosiglitazone, pioglitazone), glucagon-like peptide (GLP-1) analogues, or insulin within 3 months prior to informed consent
Treatment with anti-obesity drugs within 3 months prior to informed consent
Treatment with systemic steroids or change in dosage of thyroid hormones within 6 weeks prior to informed consent
Alcohol abuse or drug abuse
Treatment with an investigational drug within 2 months prior to informed consent
Women of child-bearing potential who are nursing or pregnant, or who are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to periodic pregnancy testing during participation in the trial

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change From Baseline in HbA1c After 12 Weeks of Treatment	Baseline and 12 weeks	Change from baseline in HbA1c after 12 weeks of treatment. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI)	Baseline and 12 weeks	Results for change of FPI from baseline at week 12 based on ANCOVA
Change of Body Weight After 12 Weeks of Treatment	Baseline and 12 weeks	Results for change of body weight after 12 weeks of treatment based on ANCOVA.
Trough Concentrations of Empagliflozin in Plasma	Days 28, 56 and 84	(Pre-dose) trough concentrations of Empagliflozin in plasma, within 30 minutes of dosing.
Change of FPG From Baseline After 12 Weeks of Treatment	Baseline and 12 weeks	Change of Fasting Plasma Glucose (FPG) from baseline after 12 weeks of treatment. Results presented stem from a repeated measures analysis. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group.
Change of HbA1c From Baseline Over Time	Baseline and weeks 4, 8 and 12	Change of HbA1c from baseline over time. Results presented stem from a repeated measures analysis.
Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment	Baseline and 12 weeks	Results for HbA1c categories at week 12 (Proportion of patients with HbA1c less than equal to 7%) based on logistic regression
Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment	Baseline and 12 weeks	Results for HbA1c categories at week 12 (Proportion of patients with HbA1c lowered at least 0.5%) based on logistic regression
Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR)	Baseline and 12 weeks	HOMA-IR (to assess insulin resistance) is defined as (FPI x FPG)/22.5. Results based on ANCOVA.
Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B)	Baseline and 12 weeks	HOMA-%B (to assess insulin beta cell function) is defined as (20 x FPI)/(FPG-3.5), FPG in mg/dl. Results are based on ANCOVA.

Trial Locations

Locations (116): 1245.10.40002 Boehringer Ingelheim Investigational Site
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Bucharest, Romania
1245.10.40004 Boehringer Ingelheim Investigational Site
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Galati, Romania
1245.10.38001 Boehringer Ingelheim Investigational Site
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Vinnitsa, Ukraine
1245.10.10028 Boehringer Ingelheim Investigational Site
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Spring Valley, California, United States
1245.10.10005 Boehringer Ingelheim Investigational Site
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Miami, Florida, United States
1245.10.10001 Boehringer Ingelheim Investigational Site
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Mission Viejo, California, United States
1245.10.10011 Boehringer Ingelheim Investigational Site
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Pasadena, California, United States
1245.10.10026 Boehringer Ingelheim Investigational Site
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Chula Vista, California, United States
1245.10.10027 Boehringer Ingelheim Investigational Site
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Walnut Creek, California, United States
1245.10.54002 Boehringer Ingelheim Investigational Site
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Capital Federal, Argentina
1245.10.10014 Boehringer Ingelheim Investigational Site
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Roswell, Georgia, United States
1245.10.10019 Boehringer Ingelheim Investigational Site
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Miami, Florida, United States
1245.10.3308A Boehringer Ingelheim Investigational Site
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Le Grau du Roi, France
1245.10.3309A Boehringer Ingelheim Investigational Site
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Nanterre Cedex, France
1245.10.3303C Boehringer Ingelheim Investigational Site
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La Rochelle Cedex 1, France
1245.10.70006 Boehringer Ingelheim Investigational Site
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St. Petersburg, Russian Federation
1245.10.34002 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
1245.10.34001 Boehringer Ingelheim Investigational Site
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Girona, Spain
1245.10.62001 Boehringer Ingelheim Investigational Site
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Nitra, Slovakia
1245.10.34004 Boehringer Ingelheim Investigational Site
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Málaga, Spain
1245.10.70004 Boehringer Ingelheim Investigational Site
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St. Petersburg, Russian Federation
1245.10.38003 Boehringer Ingelheim Investigational Site
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Kiev, Ukraine
1245.10.34010 Boehringer Ingelheim Investigational Site
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L'Hospitalet de Llobregat (Barcelona), Spain
1245.10.34005 Boehringer Ingelheim Investigational Site
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Palma (Mallorca), Spain
1245.10.38002 Boehringer Ingelheim Investigational Site
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Dnepropetrovsk, Ukraine
1245.10.38005 Boehringer Ingelheim Investigational Site
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Kharkiv, Ukraine
1245.10.3308B Boehringer Ingelheim Investigational Site
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Le Grau du Roi, France
1245.10.3303B Boehringer Ingelheim Investigational Site
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La Rochelle Cedex 1, France
1245.10.3303D Boehringer Ingelheim Investigational Site
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La Rochelle Cedex 1, France
1245.10.3311A Boehringer Ingelheim Investigational Site
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Saint Mandé, France
1245.10.3304A Boehringer Ingelheim Investigational Site
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Reims Cedex, France
1245.10.3311D Boehringer Ingelheim Investigational Site
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Saint Mandé, France
1245.10.3306A Boehringer Ingelheim Investigational Site
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Narbonne Cedex, France
1245.10.3307A Boehringer Ingelheim Investigational Site
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Quimper, France
1245.10.3305D Boehringer Ingelheim Investigational Site
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Valenciennes, France
1245.10.70002 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
1245.10.70001 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
1245.10.70003 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
1245.10.70005 Boehringer Ingelheim Investigational Site
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St. Petersburg, Russian Federation
1245.10.70007 Boehringer Ingelheim Investigational Site
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Saratov, Russian Federation
1245.10.49004 Boehringer Ingelheim Investigational Site
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Rehlingen-Siersburg, Germany
1245.10.10004 Boehringer Ingelheim Investigational Site
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Clearwarter, Florida, United States
1245.10.10021 Boehringer Ingelheim Investigational Site
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Melbourne, Florida, United States
1245.10.10016 Boehringer Ingelheim Investigational Site
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Staten Island, New York, United States
1245.10.10024 Boehringer Ingelheim Investigational Site
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St. Cloud, Florida, United States
1245.10.10009 Boehringer Ingelheim Investigational Site
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Shelby, North Carolina, United States
1245.10.10023 Boehringer Ingelheim Investigational Site
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Norristown, Pennsylvania, United States
1245.10.10010 Boehringer Ingelheim Investigational Site
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Clemson, South Carolina, United States
1245.10.54004 Boehringer Ingelheim Investigational Site
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Capital Federal, Argentina
1245.10.54008 Boehringer Ingelheim Investigational Site
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Capital Federal, Argentina
1245.10.54006 Boehringer Ingelheim Investigational Site
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Mar del Plata, Argentina
1245.10.43004 Boehringer Ingelheim Investigational Site
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Innsbruck, Austria
1245.10.43002 Boehringer Ingelheim Investigational Site
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Graz, Austria
1245.10.54005 Boehringer Ingelheim Investigational Site
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Mendoza, Argentina
1245.10.43003 Boehringer Ingelheim Investigational Site
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Wien, Austria
1245.10.43001 Boehringer Ingelheim Investigational Site
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Wien, Austria
1245.10.42001 Boehringer Ingelheim Investigational Site
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Breclav, Czech Republic
1245.10.42003 Boehringer Ingelheim Investigational Site
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Brno, Czech Republic
1245.10.37201 Boehringer Ingelheim Investigational Site
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Tallin, Estonia
1245.10.42005 Boehringer Ingelheim Investigational Site
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Brno, Czech Republic
1245.10.42002 Boehringer Ingelheim Investigational Site
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Hodonin, Czech Republic
1245.10.37202 Boehringer Ingelheim Investigational Site
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Tartu, Estonia
1245.10.58006 Boehringer Ingelheim Investigational Site
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Kerava, Finland
1245.10.58003 Boehringer Ingelheim Investigational Site
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Oulu, Finland
1245.10.3302B Boehringer Ingelheim Investigational Site
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Bondy Cedex, France
1245.10.3302A Boehringer Ingelheim Investigational Site
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Bondy Cedex, France
1245.10.58001 Boehringer Ingelheim Investigational Site
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Turku, Finland
1245.10.3310A Boehringer Ingelheim Investigational Site
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Caen Cedex 5, France
1245.10.3310C Boehringer Ingelheim Investigational Site
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Caen Cedex 5, France
1245.10.3310B Boehringer Ingelheim Investigational Site
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Caen Cedex 5, France
1245.10.3301A Boehringer Ingelheim Investigational Site
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Corbeil Essonnes, France
1245.10.3301B Boehringer Ingelheim Investigational Site
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Corbeil Essonnes, France
1245.10.3303A Boehringer Ingelheim Investigational Site
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La Rochelle Cedex 1, France
1245.10.3306B Boehringer Ingelheim Investigational Site
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Narbonne Cedex, France
1245.10.3304C Boehringer Ingelheim Investigational Site
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Reims Cedex, France
1245.10.3304B Boehringer Ingelheim Investigational Site
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Reims Cedex, France
1245.10.3305B Boehringer Ingelheim Investigational Site
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Valenciennes, France
1245.10.3311B Boehringer Ingelheim Investigational Site
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Saint Mandé, France
1245.10.3305A Boehringer Ingelheim Investigational Site
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Valenciennes, France
1245.10.3311C Boehringer Ingelheim Investigational Site
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Saint Mandé, France
1245.10.3305C Boehringer Ingelheim Investigational Site
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Valenciennes, France
1245.10.49003 Boehringer Ingelheim Investigational Site
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Frankfurt, Germany
1245.10.36001 Boehringer Ingelheim Investigational Site
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Budapest, Hungary
1245.10.36004 Boehringer Ingelheim Investigational Site
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Budapest, Hungary
1245.10.36003 Boehringer Ingelheim Investigational Site
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Budapest, Hungary
1245.10.36005 Boehringer Ingelheim Investigational Site
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Gyor, Hungary
1245.10.37101 Boehringer Ingelheim Investigational Site
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Daugavpils, Latvia
1245.10.37106 Boehringer Ingelheim Investigational Site
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Ogre, Latvia
1245.10.36002 Boehringer Ingelheim Investigational Site
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Szombathely, Hungary
1245.10.37105 Boehringer Ingelheim Investigational Site
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Kuldiga, Latvia
1245.10.37103 Boehringer Ingelheim Investigational Site
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Riga, Latvia
1245.10.49001 Boehringer Ingelheim Investigational Site
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Erlangen, Germany
1245.10.49002 Boehringer Ingelheim Investigational Site
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Hamburg, Germany
1245.10.37104 Boehringer Ingelheim Investigational Site
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Valmiera, Latvia
1245.10.47003 Boehringer Ingelheim Investigational Site
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Hamar, Norway
1245.10.37102 Boehringer Ingelheim Investigational Site
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Talsi, Latvia
1245.10.37107 Boehringer Ingelheim Investigational Site
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Riga, Latvia
1245.10.47001 Boehringer Ingelheim Investigational Site
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Stavanger, Norway
1245.10.47004 Boehringer Ingelheim Investigational Site
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Ålesund, Norway
1245.10.40001 Boehringer Ingelheim Investigational Site
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Alba Iulia, Romania
1245.10.40005 Boehringer Ingelheim Investigational Site
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Baia Mare Maramures, Romania
1245.10.62003 Boehringer Ingelheim Investigational Site
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Bratislava, Slovakia
1245.10.62002 Boehringer Ingelheim Investigational Site
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Nitra, Slovakia
1245.10.62004 Boehringer Ingelheim Investigational Site
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Presov, Slovakia
1245.10.34006 Boehringer Ingelheim Investigational Site
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Palma de Mallorca, Spain
1245.10.34008 Boehringer Ingelheim Investigational Site
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Santander, Spain
1245.10.10015 Boehringer Ingelheim Investigational Site
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Dallas, Texas, United States
1245.10.10006 Boehringer Ingelheim Investigational Site
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Wadsworth, Ohio, United States
1245.10.10012 Boehringer Ingelheim Investigational Site
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Temple, Texas, United States
1245.10.10025 Boehringer Ingelheim Investigational Site
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Federal Way, Washington, United States
1245.10.40003 Boehringer Ingelheim Investigational Site
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Brasov, Romania
1245.10.40007 Boehringer Ingelheim Investigational Site
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Bucharest, Romania
1245.10.58004 Boehringer Ingelheim Investigational Site
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Tampere, Finland
1245.10.47005 Boehringer Ingelheim Investigational Site
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Oslo, Norway
1245.10.40006 Boehringer Ingelheim Investigational Site
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Satu Mare, Romania
1245.10.38004 Boehringer Ingelheim Investigational Site
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Kharkov, Ukraine