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

NCT01778049 | Completed Phase 3 Results

• 2 other identifiers: 1275.102012-002271-34
• Study Type: interventional
• Target: 708
• Locations: 11 countries
• Sites: 114

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change From Baseline of HbA1c After 24 Weeks of Treatment.

  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 Outcomes (1)

• Fasting Plasma Glucose (FPG) Change From Baseline at 24 Weeks.

  Baseline and 24 weeks

Study Arms (8)

Empagliflozin 10 mg dose

EXPERIMENTAL

Empagliflozin open label treatment period

Drug: BI 10773

Placebo add on 10 mg dose

EXPERIMENTAL

Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo add on run-in

Drug: BI 10773 / BI 1356 Placebo; Drug: BI 10773

Empagliflozin/Linagliptin 25/5 mg Dose

EXPERIMENTAL

Empagliflozin / Linagliptin 25/5 mg Dose FDC active

Drug: BI 10773 / BI 1356; Drug: BI 10773 Placebo

Empagliflozin/Linagliptin 10/5 mg Dose.

EXPERIMENTAL

Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo

Drug: BI 10773 / BI 1356 Placebo; Drug: BI 10773

Empagliflozin/Linagliptin 10/5 mg Dose

EXPERIMENTAL

Empagliflozin / Linagliptin 10/5 mg Dose FDC active

Drug: BI 10773 Placebo; Drug: BI 10773 / BI 1356

Empagliflozin 25 mg dose

EXPERIMENTAL

Empagliflozin open label treatment period

Drug: BI 10773

Empagliflozin/Linagliptin 25/5 mg Dose.

EXPERIMENTAL

Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo

Drug: BI 10773; Drug: BI 10773 / BI 1356 Placebo

Placebo add on 25 mg dose

EXPERIMENTAL

Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo add on run-in

Drug: BI 10773; Drug: BI 10773 / BI 1356 Placebo

Interventions

BI 10773 DRUG

Empagliflozin active

Placebo add on 25 mg dose

BI 10773 Placebo DRUG

Empagliflozin placebo

Empagliflozin/Linagliptin 10/5 mg Dose

BI 10773 / BI 1356 DRUG

Empagliflozin / Linagliptin 25/5 mg Dose FDC active

Empagliflozin/Linagliptin 25/5 mg Dose

BI 10773 / BI 1356 Placebo DRUG

Empagliflozin / Linagliptin 10/5 mg Dose placebo FDC

Placebo add on 10 mg dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated ICF (Informed Consent Form)
• 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
• HBA1c (Glicoslated Hemoglobin) \> or equal to 8% and \< or equal to 10.5 % at Visit 1
• HbA1c \> or equal to 7 and \< or equal to 10.5 at Visit 4
• Age \> or equal to 18 years
• BMI (Body Mass Index) \< or equal to 45

You may not qualify if:

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

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (114)

1275.10.01019 Boehringer Ingelheim Investigational Site

Chino, California, United States

Location

1275.10.01008 Boehringer Ingelheim Investigational Site

Huntington Beach, California, United States

Location

1275.10.01003 Boehringer Ingelheim Investigational Site

San Diego, California, United States

Location

1275.10.01024 Boehringer Ingelheim Investigational Site

San Diego, California, United States

Location

1275.10.01002 Boehringer Ingelheim Investigational Site

Sylmar, California, United States

Location

1275.10.01011 Boehringer Ingelheim Investigational Site

Miami, Florida, United States

Location

1275.10.01009 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

Location

1275.10.01023 Boehringer Ingelheim Investigational Site

Oviedo, Florida, United States

Location

1275.10.01006 Boehringer Ingelheim Investigational Site

Tamarac, Florida, United States

Location

1275.10.01017 Boehringer Ingelheim Investigational Site

Conyers, Georgia, United States

Location

1275.10.01016 Boehringer Ingelheim Investigational Site

Snellville, Georgia, United States

Location

1275.10.01012 Boehringer Ingelheim Investigational Site

Avon, Indiana, United States

Location

1275.10.01013 Boehringer Ingelheim Investigational Site

Muncie, Indiana, United States

Location

1275.10.01010 Boehringer Ingelheim Investigational Site

Elkton, Maryland, United States

Location

1275.10.01001 Boehringer Ingelheim Investigational Site

Stevensville, Michigan, United States

Location

1275.10.01007 Boehringer Ingelheim Investigational Site

Salisbury, North Carolina, United States

Location

1275.10.01005 Boehringer Ingelheim Investigational Site

Bismarck, North Dakota, United States

Location

1275.10.01020 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

1275.10.01022 Boehringer Ingelheim Investigational Site

Pittsburgh, Pennsylvania, United States

Location

1275.10.01021 Boehringer Ingelheim Investigational Site

Union, South Carolina, United States

Location

1275.10.01014 Boehringer Ingelheim Investigational Site

North Richland Hills, Texas, United States

Location

1275.10.01018 Boehringer Ingelheim Investigational Site

Draper, Utah, United States

Location

1275.10.01015 Boehringer Ingelheim Investigational Site

Richmond, Virginia, United States

Location

1275.10.01025 Boehringer Ingelheim Investigational Site

Virginia Beach, Virginia, United States

Location

1275.10.54005 Boehringer Ingelheim Investigational Site

Caba, Argentina

Location

1275.10.54012 Boehringer Ingelheim Investigational Site

Caba, Argentina

Location

1275.10.54002 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1275.10.54007 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1275.10.54013 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1275.10.54006 Boehringer Ingelheim Investigational Site

Córdoba, Argentina

Location

1275.10.54008 Boehringer Ingelheim Investigational Site

Córdoba, Argentina

Location

1275.10.54011 Boehringer Ingelheim Investigational Site

Córdoba, Argentina

Location

1275.10.54003 Boehringer Ingelheim Investigational Site

Godoy Cruz, Mendoza, Argentina

Location

1275.10.54009 Boehringer Ingelheim Investigational Site

Mar del Plata, Argentina

Location

1275.10.54004 Boehringer Ingelheim Investigational Site

Salta, Argentina

Location

1275.10.54001 Boehringer Ingelheim Investigational Site

San Isidro, Argentina

Location

1275.10.54010 Boehringer Ingelheim Investigational Site

Zárate, Argentina

Location

1275.10.61008 Boehringer Ingelheim Investigational Site

Cardiff, New South Wales, Australia

Location

1275.10.61002 Boehringer Ingelheim Investigational Site

East Ringwood, Victoria, Australia

Location

1275.10.61001 Boehringer Ingelheim Investigational Site

Heidelberg Heights, Victoria, Australia

Location

1275.10.61009 Boehringer Ingelheim Investigational Site

Mirrabooka, Western Australia, Australia

Location

1275.10.02004 Boehringer Ingelheim Investigational Site

Edmonton, Alberta, Canada

Location

1275.10.02001 Boehringer Ingelheim Investigational Site

Red Deer, Alberta, Canada

Location

1275.10.02003 Boehringer Ingelheim Investigational Site

Chilliwack, British Columbia, Canada

Location

1275.10.02009 Boehringer Ingelheim Investigational Site

Coquitlam, British Columbia, Canada

Location

1275.10.02012 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1275.10.02006 Boehringer Ingelheim Investigational Site

Winnipeg, Manitoba, Canada

Location

1275.10.02008 Boehringer Ingelheim Investigational Site

Winnipeg, Manitoba, Canada

Location

1275.10.02005 Boehringer Ingelheim Investigational Site

Moncton, New Brunswick, Canada

Location

1275.10.02013 Boehringer Ingelheim Investigational Site

Burlington, Ontario, Canada

Location

1275.10.02007 Boehringer Ingelheim Investigational Site

Greater Sudbury, Ontario, Canada

Location

1275.10.02002 Boehringer Ingelheim Investigational Site

Strathroy, Ontario, Canada

Location

1275.10.02011 Boehringer Ingelheim Investigational Site

Drummondville, Quebec, Canada

Location

1275.10.02010 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

1275.10.34014 Boehringer Ingelheim Investigational Site

Ávila, El Salvador

Location

1275.10.49007 Boehringer Ingelheim Investigational Site

Aßlar, Germany

Location

1275.10.49014 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1275.10.49004 Boehringer Ingelheim Investigational Site

Cologne, Germany

Location

1275.10.49016 Boehringer Ingelheim Investigational Site

Elsterwerda, Germany

Location

1275.10.49012 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1275.10.49005 Boehringer Ingelheim Investigational Site

Hatten, Germany

Location

1275.10.49008 Boehringer Ingelheim Investigational Site

Kiel Kronshagen, Germany

Location

1275.10.49010 Boehringer Ingelheim Investigational Site

Lübeck, Germany

Location

1275.10.49003 Boehringer Ingelheim Investigational Site

Münster, Germany

Location

1275.10.49006 Boehringer Ingelheim Investigational Site

Pirna, Germany

Location

1275.10.49013 Boehringer Ingelheim Investigational Site

Saint Ingbert/Oberwürzbach, Germany

Location

1275.10.49001 Boehringer Ingelheim Investigational Site

Unterschneidheim, Germany

Location

1275.10.49015 Boehringer Ingelheim Investigational Site

Wangen, Germany

Location

1275.10.39005 Boehringer Ingelheim Investigational Site

Ancona, Italy

Location

1275.10.39006 Boehringer Ingelheim Investigational Site

Catania, Italy

Location

1275.10.39009 Boehringer Ingelheim Investigational Site

Catania, Italy

Location

1275.10.39014 Boehringer Ingelheim Investigational Site

Catania, Italy

Location

1275.10.39007 Boehringer Ingelheim Investigational Site

Latina, Italy

Location

1275.10.39012 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1275.10.39013 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1275.10.39015 Boehringer Ingelheim Investigational Site

Olbia (OT), Italy

Location

1275.10.39016 Boehringer Ingelheim Investigational Site

Orbassano (TO), Italy

Location

1275.10.39004 Boehringer Ingelheim Investigational Site

Palermo, Italy

Location

1275.10.39003 Boehringer Ingelheim Investigational Site

Pistoia, Italy

Location

1275.10.39008 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1275.10.39001 Boehringer Ingelheim Investigational Site

Sesto San Giovanni (MI), Italy

Location

1275.10.39010 Boehringer Ingelheim Investigational Site

Siena, Italy

Location

1275.10.39011 Boehringer Ingelheim Investigational Site

Terni, Italy

Location

1275.10.35104 Boehringer Ingelheim Investigational Site

Cantanhede, Portugal

Location

1275.10.35112 Boehringer Ingelheim Investigational Site

Porto, Portugal

Location

1275.10.35103 Boehringer Ingelheim Investigational Site

Sandim, Portugal

Location

1275.10.35105 Boehringer Ingelheim Investigational Site

Tornada, Portugal

Location

1275.10.35108 Boehringer Ingelheim Investigational Site

Valadares, Portugal

Location

1275.10.35101 Boehringer Ingelheim Investigational Site

Vila Nova de Gaia, Portugal

Location

1275.10.07004 Boehringer Ingelheim Investigational Site

Chelyabinsk, Russia

Location

1275.10.07003 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

1275.10.07006 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

1275.10.07001 Boehringer Ingelheim Investigational Site

Saratov, Russia

Location

1275.10.07005 Boehringer Ingelheim Investigational Site

Saratov, Russia

Location

1275.10.07002 Boehringer Ingelheim Investigational Site

Yaroslavl, Russia

Location

1275.10.34003 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1275.10.34004 Boehringer Ingelheim Investigational Site

Canet de Mar, Spain

Location

1275.10.34008 Boehringer Ingelheim Investigational Site

Centelles, Spain

Location

1275.10.34009 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat (Barcelona), Spain

Location

1275.10.34012 Boehringer Ingelheim Investigational Site

La Roca del Vallès, Spain

Location

1275.10.34006 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1275.10.34011 Boehringer Ingelheim Investigational Site

Mataró, Spain

Location

1275.10.34001 Boehringer Ingelheim Investigational Site

Málaga, Spain

Location

1275.10.34010 Boehringer Ingelheim Investigational Site

Málaga, Spain

Location

1275.10.34013 Boehringer Ingelheim Investigational Site

Pineda de Mar, Spain

Location

1275.10.34002 Boehringer Ingelheim Investigational Site

Sabadell, Spain

Location

1275.10.34005 Boehringer Ingelheim Investigational Site

Tarragona, Spain

Location

1275.10.38006 Boehringer Ingelheim Investigational Site

Chernivtsi, Ukraine

Location

1275.10.38007 Boehringer Ingelheim Investigational Site

Dnipro, Ukraine

Location

1275.10.38002 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

1275.10.38003 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

1275.10.38004 Boehringer Ingelheim Investigational Site

Lviv, Ukraine

Location

1275.10.38001 Boehringer Ingelheim Investigational Site

Vinnitsa, Ukraine

Location

1275.10.38005 Boehringer Ingelheim Investigational Site

Zhytomyr, Ukraine

Location

Related Publications (1)

• Tinahones FJ, Gallwitz B, Nordaby M, Gotz S, Maldonado-Lutomirsky M, Woerle HJ, Broedl UC. Linagliptin as add-on to empagliflozin and metformin in patients with type 2 diabetes: Two 24-week randomized, double-blind, double-dummy, parallel-group trials. Diabetes Obes Metab. 2017 Feb;19(2):266-274. doi: 10.1111/dom.12814. Epub 2016 Nov 24.

  PMID: 27762093 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; Linagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2013
• First Posted: January 29, 2013
• Study Start: January 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: April 4, 2016
• Results First Posted: April 4, 2016

Record last verified: 2016-03

Locations

US (24); AR (13); RU (6); CA (13); ES (12); IT (15); DE (13); AU (4); EL (1); UA (7); PT (6)