Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Background Metformin in Patient With Type 2 Diabetes

March 4, 2016 updated by: Boehringer Ingelheim

A Phase III, Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Linagliptin 5 mg Compared to Placebo, Administered as Oral Fixed Dose Combination With Empagliflozin 10 mg or 25 mg for 24 Weeks, in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control After 16 Weeks of Treatment With Empagliflozin 10 mg or 25 mg on Metformin Background Therapy

The objective of the study is to investigate the efficacy, safety and tolerability of linagliptin 5 mg qd compared to placebo given for 24 weeks in inadequately controlled T2DM patients on empagliflozin 10 mg or 25 mg and maximum tolerated dose of metformin. The primary objective of efficacy evaluation is planned after 24 weeks of treatment. The study is designed to show superiority of the combination of empagliflozin and linagliptin over empagliflozin alone.

Study Overview

Study Type

Interventional

Enrollment (Actual)

708

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Caba, Argentina
        • 1275.10.54005 Boehringer Ingelheim Investigational Site
      • Caba, Argentina
        • 1275.10.54012 Boehringer Ingelheim Investigational Site
      • Capital Federal, Argentina
        • 1275.10.54002 Boehringer Ingelheim Investigational Site
      • Capital Federal, Argentina
        • 1275.10.54007 Boehringer Ingelheim Investigational Site
      • Capital Federal, Argentina
        • 1275.10.54013 Boehringer Ingelheim Investigational Site
      • Cordoba, Argentina
        • 1275.10.54006 Boehringer Ingelheim Investigational Site
      • Cordoba, Argentina
        • 1275.10.54008 Boehringer Ingelheim Investigational Site
      • Córdoba, Argentina
        • 1275.10.54011 Boehringer Ingelheim Investigational Site
      • Godoy Cruz, Mendoza, Argentina
        • 1275.10.54003 Boehringer Ingelheim Investigational Site
      • Mar del Plata, Argentina
        • 1275.10.54009 Boehringer Ingelheim Investigational Site
      • Salta, Argentina
        • 1275.10.54004 Boehringer Ingelheim Investigational Site
      • San Isidro, Argentina
        • 1275.10.54001 Boehringer Ingelheim Investigational Site
      • Zarate, Argentina
        • 1275.10.54010 Boehringer Ingelheim Investigational Site
    • New South Wales
      • Cardiff, New South Wales, Australia
        • 1275.10.61008 Boehringer Ingelheim Investigational Site
    • Victoria
      • East Ringwood, Victoria, Australia
        • 1275.10.61002 Boehringer Ingelheim Investigational Site
      • Heidelberg Heights, Victoria, Australia
        • 1275.10.61001 Boehringer Ingelheim Investigational Site
    • Western Australia
      • Mirrabooka, Western Australia, Australia
        • 1275.10.61009 Boehringer Ingelheim Investigational Site
    • Alberta
      • Edmonton, Alberta, Canada
        • 1275.10.02004 Boehringer Ingelheim Investigational Site
      • Red Deer, Alberta, Canada
        • 1275.10.02001 Boehringer Ingelheim Investigational Site
    • British Columbia
      • Chilliwack, British Columbia, Canada
        • 1275.10.02003 Boehringer Ingelheim Investigational Site
      • Coquitlam, British Columbia, Canada
        • 1275.10.02009 Boehringer Ingelheim Investigational Site
      • Vancouver, British Columbia, Canada
        • 1275.10.02012 Boehringer Ingelheim Investigational Site
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • 1275.10.02006 Boehringer Ingelheim Investigational Site
      • Winnipeg, Manitoba, Canada
        • 1275.10.02008 Boehringer Ingelheim Investigational Site
    • New Brunswick
      • Moncton, New Brunswick, Canada
        • 1275.10.02005 Boehringer Ingelheim Investigational Site
    • Ontario
      • Burlington, Ontario, Canada
        • 1275.10.02013 Boehringer Ingelheim Investigational Site
      • Strathroy, Ontario, Canada
        • 1275.10.02002 Boehringer Ingelheim Investigational Site
      • Sudbury, Ontario, Canada
        • 1275.10.02007 Boehringer Ingelheim Investigational Site
    • Quebec
      • Drummondville, Quebec, Canada
        • 1275.10.02011 Boehringer Ingelheim Investigational Site
      • Montreal, Quebec, Canada
        • 1275.10.02010 Boehringer Ingelheim Investigational Site
      • Ávila, El Salvador
        • 1275.10.34014 Boehringer Ingelheim Investigational Site
      • Asslar, Germany
        • 1275.10.49007 Boehringer Ingelheim Investigational Site
      • Berlin, Germany
        • 1275.10.49014 Boehringer Ingelheim Investigational Site
      • Elsterwerda, Germany
        • 1275.10.49016 Boehringer Ingelheim Investigational Site
      • Hamburg, Germany
        • 1275.10.49012 Boehringer Ingelheim Investigational Site
      • Hatten, Germany
        • 1275.10.49005 Boehringer Ingelheim Investigational Site
      • Kiel Kronshagen, Germany
        • 1275.10.49008 Boehringer Ingelheim Investigational Site
      • Köln, Germany
        • 1275.10.49004 Boehringer Ingelheim Investigational Site
      • Lübeck, Germany
        • 1275.10.49010 Boehringer Ingelheim Investigational Site
      • Münster, Germany
        • 1275.10.49003 Boehringer Ingelheim Investigational Site
      • Pirna, Germany
        • 1275.10.49006 Boehringer Ingelheim Investigational Site
      • St. Ingbert/Oberwürzbach, Germany
        • 1275.10.49013 Boehringer Ingelheim Investigational Site
      • Unterschneidheim, Germany
        • 1275.10.49001 Boehringer Ingelheim Investigational Site
      • Wangen, Germany
        • 1275.10.49015 Boehringer Ingelheim Investigational Site
      • Ancona, Italy
        • 1275.10.39005 Boehringer Ingelheim Investigational Site
      • Catania, Italy
        • 1275.10.39006 Boehringer Ingelheim Investigational Site
      • Catania, Italy
        • 1275.10.39009 Boehringer Ingelheim Investigational Site
      • Catania, Italy
        • 1275.10.39014 Boehringer Ingelheim Investigational Site
      • Latina, Italy
        • 1275.10.39007 Boehringer Ingelheim Investigational Site
      • Milano, Italy
        • 1275.10.39012 Boehringer Ingelheim Investigational Site
      • Milano, Italy
        • 1275.10.39013 Boehringer Ingelheim Investigational Site
      • Olbia (OT), Italy
        • 1275.10.39015 Boehringer Ingelheim Investigational Site
      • Orbassano (TO), Italy
        • 1275.10.39016 Boehringer Ingelheim Investigational Site
      • Palermo, Italy
        • 1275.10.39004 Boehringer Ingelheim Investigational Site
      • Pistoia, Italy
        • 1275.10.39003 Boehringer Ingelheim Investigational Site
      • Roma, Italy
        • 1275.10.39008 Boehringer Ingelheim Investigational Site
      • Sesto San Giovanni (MI), Italy
        • 1275.10.39001 Boehringer Ingelheim Investigational Site
      • Siena, Italy
        • 1275.10.39010 Boehringer Ingelheim Investigational Site
      • Terni, Italy
        • 1275.10.39011 Boehringer Ingelheim Investigational Site
      • Cantanhede, Portugal
        • 1275.10.35104 Boehringer Ingelheim Investigational Site
      • Porto, Portugal
        • 1275.10.35112 Boehringer Ingelheim Investigational Site
      • Sandim, Portugal
        • 1275.10.35103 Boehringer Ingelheim Investigational Site
      • Tornada, Portugal
        • 1275.10.35105 Boehringer Ingelheim Investigational Site
      • Valadares, Portugal
        • 1275.10.35108 Boehringer Ingelheim Investigational Site
      • Vila Nova de Gaia, Portugal
        • 1275.10.35101 Boehringer Ingelheim Investigational Site
      • Chelyabinsk, Russian Federation
        • 1275.10.07004 Boehringer Ingelheim Investigational Site
      • Saint-Petersburg, Russian Federation
        • 1275.10.07006 Boehringer Ingelheim Investigational Site
      • Saratov, Russian Federation
        • 1275.10.07001 Boehringer Ingelheim Investigational Site
      • Saratov, Russian Federation
        • 1275.10.07005 Boehringer Ingelheim Investigational Site
      • St. Petersburg, Russian Federation
        • 1275.10.07003 Boehringer Ingelheim Investigational Site
      • Yaroslavl, Russian Federation
        • 1275.10.07002 Boehringer Ingelheim Investigational Site
      • Barcelona, Spain
        • 1275.10.34003 Boehringer Ingelheim Investigational Site
      • Canet de Mar, Spain
        • 1275.10.34004 Boehringer Ingelheim Investigational Site
      • Centelles, Spain
        • 1275.10.34008 Boehringer Ingelheim Investigational Site
      • L'Hospitalet de Llobregat (Barcelona), Spain
        • 1275.10.34009 Boehringer Ingelheim Investigational Site
      • La Roca del Vallès, Spain
        • 1275.10.34012 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1275.10.34006 Boehringer Ingelheim Investigational Site
      • Malaga, Spain
        • 1275.10.34010 Boehringer Ingelheim Investigational Site
      • Mataró, Spain
        • 1275.10.34011 Boehringer Ingelheim Investigational Site
      • Málaga, Spain
        • 1275.10.34001 Boehringer Ingelheim Investigational Site
      • Pineda de Mar, Spain
        • 1275.10.34013 Boehringer Ingelheim Investigational Site
      • Sabadell, Spain
        • 1275.10.34002 Boehringer Ingelheim Investigational Site
      • Tarragona, Spain
        • 1275.10.34005 Boehringer Ingelheim Investigational Site
      • Chernivtsi, Ukraine
        • 1275.10.38006 Boehringer Ingelheim Investigational Site
      • Dnipropetrovs'k, Ukraine
        • 1275.10.38007 Boehringer Ingelheim Investigational Site
      • Kiev, Ukraine
        • 1275.10.38002 Boehringer Ingelheim Investigational Site
      • Kiev, Ukraine
        • 1275.10.38003 Boehringer Ingelheim Investigational Site
      • Lviv, Ukraine
        • 1275.10.38004 Boehringer Ingelheim Investigational Site
      • Vinnitsa, Ukraine
        • 1275.10.38001 Boehringer Ingelheim Investigational Site
      • Zhytomyr, Ukraine
        • 1275.10.38005 Boehringer Ingelheim Investigational Site
    • California
      • Chino, California, United States
        • 1275.10.01019 Boehringer Ingelheim Investigational Site
      • Huntington Beach, California, United States
        • 1275.10.01008 Boehringer Ingelheim Investigational Site
      • San Diego, California, United States
        • 1275.10.01003 Boehringer Ingelheim Investigational Site
      • San Diego, California, United States
        • 1275.10.01024 Boehringer Ingelheim Investigational Site
      • Sylmar, California, United States
        • 1275.10.01002 Boehringer Ingelheim Investigational Site
    • Florida
      • Miami, Florida, United States
        • 1275.10.01011 Boehringer Ingelheim Investigational Site
      • Orlando, Florida, United States
        • 1275.10.01009 Boehringer Ingelheim Investigational Site
      • Oviedo, Florida, United States
        • 1275.10.01023 Boehringer Ingelheim Investigational Site
      • Tamarac, Florida, United States
        • 1275.10.01006 Boehringer Ingelheim Investigational Site
    • Georgia
      • Conyers, Georgia, United States
        • 1275.10.01017 Boehringer Ingelheim Investigational Site
      • Snellville, Georgia, United States
        • 1275.10.01016 Boehringer Ingelheim Investigational Site
    • Indiana
      • Avon, Indiana, United States
        • 1275.10.01012 Boehringer Ingelheim Investigational Site
      • Muncie, Indiana, United States
        • 1275.10.01013 Boehringer Ingelheim Investigational Site
    • Maryland
      • Elkton, Maryland, United States
        • 1275.10.01010 Boehringer Ingelheim Investigational Site
    • Michigan
      • Stevensville, Michigan, United States
        • 1275.10.01001 Boehringer Ingelheim Investigational Site
    • North Carolina
      • Salisbury, North Carolina, United States
        • 1275.10.01007 Boehringer Ingelheim Investigational Site
    • North Dakota
      • Bismarck, North Dakota, United States
        • 1275.10.01005 Boehringer Ingelheim Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
        • 1275.10.01020 Boehringer Ingelheim Investigational Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States
        • 1275.10.01022 Boehringer Ingelheim Investigational Site
    • South Carolina
      • Union, South Carolina, United States
        • 1275.10.01021 Boehringer Ingelheim Investigational Site
    • Texas
      • North Richland Hills, Texas, United States
        • 1275.10.01014 Boehringer Ingelheim Investigational Site
    • Utah
      • Draper, Utah, United States
        • 1275.10.01018 Boehringer Ingelheim Investigational Site
    • Virginia
      • Richmond, Virginia, United States
        • 1275.10.01015 Boehringer Ingelheim Investigational Site
      • Virginia Beach, Virginia, United States
        • 1275.10.01025 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. Signed and dated ICF (Informed Consent Form)
  2. Male or female on diet and exercise regime and on stable background metformin > or equal to 1500 mg or maximun dose according to local label
  3. HBA1c (Glicoslated Hemoglobin) > or equal to 8% and < or equal to 10.5 % at Visit 1
  4. HbA1c > or equal to 7 and < or equal to 10.5 at Visit 4
  5. Age > or equal to 18 years
  6. BMI (Body Mass Index) < or equal to 45

Exclusion criteria:

  1. Uncontrolled hyperglycemia during open label period and placebo add on "run-in" period
  2. Use of any other antidiabetic
  3. Renal function below 60 ml/min/1.73 m2
  4. Antiobesity drugs or aggresive diets
  5. Gastorintestinal surgeries
  6. Current systemic steroids or uncontrolled endocrine disorders other than Diabetes Type 2
  7. Acute coronary syndrome and stroke within 3 months of informed consent
  8. Known allergies to DPP-IV (Dypeptidil Peptidase IV) or SGLT-2 (Sodium Glucose Transporter 2) inhibitors

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Empagliflozin 10 mg dose
Empagliflozin open label treatment period
Empagliflozin active
Experimental: Placebo add on 10 mg dose
Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo add on run-in
Empagliflozin active
Empagliflozin / Linagliptin 10/5 mg Dose placebo FDC
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo
Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo
Experimental: Empagliflozin/Linagliptin 25/5 mg Dose
Empagliflozin / Linagliptin 25/5 mg Dose FDC active
Empagliflozin placebo
Empagliflozin / Linagliptin 25/5 mg Dose FDC active
Empagliflozin / Linagliptin 10/5 mg Dose FDC active
Experimental: Empagliflozin/Linagliptin 10/5 mg Dose.
Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo
Empagliflozin active
Empagliflozin / Linagliptin 10/5 mg Dose placebo FDC
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo
Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo
Experimental: Empagliflozin/Linagliptin 10/5 mg Dose
Empagliflozin / Linagliptin 10/5 mg Dose FDC active
Empagliflozin placebo
Empagliflozin / Linagliptin 25/5 mg Dose FDC active
Empagliflozin / Linagliptin 10/5 mg Dose FDC active
Experimental: Empagliflozin 25 mg dose
Empagliflozin open label treatment period
Empagliflozin active
Experimental: Empagliflozin/Linagliptin 25/5 mg Dose.
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo
Empagliflozin active
Empagliflozin / Linagliptin 10/5 mg Dose placebo FDC
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo
Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo
Experimental: Placebo add on 25 mg dose
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo add on run-in
Empagliflozin active
Empagliflozin / Linagliptin 10/5 mg Dose placebo FDC
Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo
Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline of HbA1c After 24 Weeks of Treatment.
Time Frame: Baseline and 24 weeks

Change from baseline in Glycated haemoglobin (HbA1c) [%] after 24 weeks of treatment with double-blind trial medication, i.e. HbA1c change from baseline at Week 24. The term "baseline" was not used to refer to measurements prior to the administration of open-label medication. Such measurements were referred to as "pre-treatment". Analyses of change from pre-treatment used the last value before first administration of open-label medication as point of reference.

Observed Case (OC): This method analyse only available data that were observed while patients were on treatment, i.e., excluding the missing data. All values measured after rescue medication taken were set to missing. Full Analysis Set (FAS): Includes all patients in the Treated set who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the double-blind part of the trial.

Baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fasting Plasma Glucose (FPG) Change From Baseline at 24 Weeks.
Time Frame: Baseline and 24 weeks
Change from baseline FPG (mmol/L) after 24 weeks of treatment with double-blind trial medication, i.e. FPG change from baseline at Week 24.
Baseline and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2015

Study Registration Dates

First Submitted

January 24, 2013

First Submitted That Met QC Criteria

January 28, 2013

First Posted (Estimate)

January 29, 2013

Study Record Updates

Last Update Posted (Estimate)

April 4, 2016

Last Update Submitted That Met QC Criteria

March 4, 2016

Last Verified

March 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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