Clinical trial NCT01778049: Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Background Metformin in Patient With Type 2 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2013-01-29
Enrollment: 708
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline of HbA1c After 24 Weeks of Treatment.
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: Fasting Plasma Glucose (FPG) Change From Baseline at 24 Weeks.
timeFrame: Baseline and 24 weeks
Other outcomes:
Locations:
city: Chino
country: United States
facility: 1275.10.01019 Boehringer Ingelheim Investigational Site
state: California
city: Huntington Beach
country: United States
facility: 1275.10.01008 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1275.10.01003 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1275.10.01024 Boehringer Ingelheim Investigational Site
state: California
city: Sylmar
country: United States
facility: 1275.10.01002 Boehringer Ingelheim Investigational Site
state: California
city: Miami
country: United States
facility: 1275.10.01011 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1275.10.01009 Boehringer Ingelheim Investigational Site
state: Florida
city: Oviedo
country: United States
facility: 1275.10.01023 Boehringer Ingelheim Investigational Site
state: Florida
city: Tamarac
country: United States
facility: 1275.10.01006 Boehringer Ingelheim Investigational Site
state: Florida
city: Conyers
country: United States
facility: 1275.10.01017 Boehringer Ingelheim Investigational Site
state: Georgia
city: Snellville
country: United States
facility: 1275.10.01016 Boehringer Ingelheim Investigational Site
state: Georgia
city: Avon
country: United States
facility: 1275.10.01012 Boehringer Ingelheim Investigational Site
state: Indiana
city: Muncie
country: United States
facility: 1275.10.01013 Boehringer Ingelheim Investigational Site
state: Indiana
city: Elkton
country: United States
facility: 1275.10.01010 Boehringer Ingelheim Investigational Site
state: Maryland
city: Stevensville
country: United States
facility: 1275.10.01001 Boehringer Ingelheim Investigational Site
state: Michigan
city: Salisbury
country: United States
facility: 1275.10.01007 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Bismarck
country: United States
facility: 1275.10.01005 Boehringer Ingelheim Investigational Site
state: North Dakota
city: Oklahoma City
country: United States
facility: 1275.10.01020 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Pittsburgh
country: United States
facility: 1275.10.01022 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Union
country: United States
facility: 1275.10.01021 Boehringer Ingelheim Investigational Site
state: South Carolina
city: North Richland Hills
country: United States
facility: 1275.10.01014 Boehringer Ingelheim Investigational Site
state: Texas
city: Draper
country: United States
facility: 1275.10.01018 Boehringer Ingelheim Investigational Site
state: Utah
city: Richmond
country: United States
facility: 1275.10.01015 Boehringer Ingelheim Investigational Site
state: Virginia
city: Virginia Beach
country: United States
facility: 1275.10.01025 Boehringer Ingelheim Investigational Site
state: Virginia
city: Caba
country: Argentina
facility: 1275.10.54005 Boehringer Ingelheim Investigational Site
city: Caba
country: Argentina
facility: 1275.10.54012 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 1275.10.54002 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 1275.10.54007 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 1275.10.54013 Boehringer Ingelheim Investigational Site
city: Cordoba
country: Argentina
facility: 1275.10.54006 Boehringer Ingelheim Investigational Site
city: Cordoba
country: Argentina
facility: 1275.10.54008 Boehringer Ingelheim Investigational Site
city: Córdoba
country: Argentina
facility: 1275.10.54011 Boehringer Ingelheim Investigational Site
city: Godoy Cruz, Mendoza
country: Argentina
facility: 1275.10.54003 Boehringer Ingelheim Investigational Site
city: Mar del Plata
country: Argentina
facility: 1275.10.54009 Boehringer Ingelheim Investigational Site
city: Salta
country: Argentina
facility: 1275.10.54004 Boehringer Ingelheim Investigational Site
city: San Isidro
country: Argentina
facility: 1275.10.54001 Boehringer Ingelheim Investigational Site
city: Zarate
country: Argentina
facility: 1275.10.54010 Boehringer Ingelheim Investigational Site
city: Cardiff
country: Australia
facility: 1275.10.61008 Boehringer Ingelheim Investigational Site
state: New South Wales
city: East Ringwood
country: Australia
facility: 1275.10.61002 Boehringer Ingelheim Investigational Site
state: Victoria
city: Heidelberg Heights
country: Australia
facility: 1275.10.61001 Boehringer Ingelheim Investigational Site
state: Victoria
city: Mirrabooka
country: Australia
facility: 1275.10.61009 Boehringer Ingelheim Investigational Site
state: Western Australia
city: Edmonton
country: Canada
facility: 1275.10.02004 Boehringer Ingelheim Investigational Site
state: Alberta
city: Red Deer
country: Canada
facility: 1275.10.02001 Boehringer Ingelheim Investigational Site
state: Alberta
city: Chilliwack
country: Canada
facility: 1275.10.02003 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Coquitlam
country: Canada
facility: 1275.10.02009 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1275.10.02012 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: 1275.10.02006 Boehringer Ingelheim Investigational Site
state: Manitoba
city: Winnipeg
country: Canada
facility: 1275.10.02008 Boehringer Ingelheim Investigational Site
state: Manitoba
city: Moncton
country: Canada
facility: 1275.10.02005 Boehringer Ingelheim Investigational Site
state: New Brunswick
city: Burlington
country: Canada
facility: 1275.10.02013 Boehringer Ingelheim Investigational Site
state: Ontario
city: Strathroy
country: Canada
facility: 1275.10.02002 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: 1275.10.02007 Boehringer Ingelheim Investigational Site
state: Ontario
city: Drummondville
country: Canada
facility: 1275.10.02011 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 1275.10.02010 Boehringer Ingelheim Investigational Site
state: Quebec
city: Ávila
country: El Salvador
facility: 1275.10.34014 Boehringer Ingelheim Investigational Site
city: Asslar
country: Germany
facility: 1275.10.49007 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1275.10.49014 Boehringer Ingelheim Investigational Site
city: Elsterwerda
country: Germany
facility: 1275.10.49016 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1275.10.49012 Boehringer Ingelheim Investigational Site
city: Hatten
country: Germany
facility: 1275.10.49005 Boehringer Ingelheim Investigational Site
city: Kiel Kronshagen
country: Germany
facility: 1275.10.49008 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 1275.10.49004 Boehringer Ingelheim Investigational Site
city: Lübeck
country: Germany
facility: 1275.10.49010 Boehringer Ingelheim Investigational Site
city: Münster
country: Germany
facility: 1275.10.49003 Boehringer Ingelheim Investigational Site
city: Pirna
country: Germany
facility: 1275.10.49006 Boehringer Ingelheim Investigational Site
city: St. Ingbert/Oberwürzbach
country: Germany
facility: 1275.10.49013 Boehringer Ingelheim Investigational Site
city: Unterschneidheim
country: Germany
facility: 1275.10.49001 Boehringer Ingelheim Investigational Site
city: Wangen
country: Germany
facility: 1275.10.49015 Boehringer Ingelheim Investigational Site
city: Ancona
country: Italy
facility: 1275.10.39005 Boehringer Ingelheim Investigational Site
city: Catania
country: Italy
facility: 1275.10.39006 Boehringer Ingelheim Investigational Site
city: Catania
country: Italy
facility: 1275.10.39009 Boehringer Ingelheim Investigational Site
city: Catania
country: Italy
facility: 1275.10.39014 Boehringer Ingelheim Investigational Site
city: Latina
country: Italy
facility: 1275.10.39007 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1275.10.39012 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1275.10.39013 Boehringer Ingelheim Investigational Site
city: Olbia (OT)
country: Italy
facility: 1275.10.39015 Boehringer Ingelheim Investigational Site
city: Orbassano (TO)
country: Italy
facility: 1275.10.39016 Boehringer Ingelheim Investigational Site
city: Palermo
country: Italy
facility: 1275.10.39004 Boehringer Ingelheim Investigational Site
city: Pistoia
country: Italy
facility: 1275.10.39003 Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: 1275.10.39008 Boehringer Ingelheim Investigational Site
city: Sesto San Giovanni (MI)
country: Italy
facility: 1275.10.39001 Boehringer Ingelheim Investigational Site
city: Siena
country: Italy
facility: 1275.10.39010 Boehringer Ingelheim Investigational Site
city: Terni
country: Italy
facility: 1275.10.39011 Boehringer Ingelheim Investigational Site
city: Cantanhede
country: Portugal
facility: 1275.10.35104 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1275.10.35112 Boehringer Ingelheim Investigational Site
city: Sandim
country: Portugal
facility: 1275.10.35103 Boehringer Ingelheim Investigational Site
city: Tornada
country: Portugal
facility: 1275.10.35105 Boehringer Ingelheim Investigational Site
city: Valadares
country: Portugal
facility: 1275.10.35108 Boehringer Ingelheim Investigational Site
city: Vila Nova de Gaia
country: Portugal
facility: 1275.10.35101 Boehringer Ingelheim Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: 1275.10.07004 Boehringer Ingelheim Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: 1275.10.07006 Boehringer Ingelheim Investigational Site
city: Saratov
country: Russian Federation
facility: 1275.10.07001 Boehringer Ingelheim Investigational Site
city: Saratov
country: Russian Federation
facility: 1275.10.07005 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1275.10.07003 Boehringer Ingelheim Investigational Site
city: Yaroslavl
country: Russian Federation
facility: 1275.10.07002 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1275.10.34003 Boehringer Ingelheim Investigational Site
city: Canet de Mar
country: Spain
facility: 1275.10.34004 Boehringer Ingelheim Investigational Site
city: Centelles
country: Spain
facility: 1275.10.34008 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat (Barcelona)
country: Spain
facility: 1275.10.34009 Boehringer Ingelheim Investigational Site
city: La Roca del Vallès
country: Spain
facility: 1275.10.34012 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1275.10.34006 Boehringer Ingelheim Investigational Site
city: Malaga
country: Spain
facility: 1275.10.34010 Boehringer Ingelheim Investigational Site
city: Mataró
country: Spain
facility: 1275.10.34011 Boehringer Ingelheim Investigational Site
city: Málaga
country: Spain
facility: 1275.10.34001 Boehringer Ingelheim Investigational Site
city: Pineda de Mar
country: Spain
facility: 1275.10.34013 Boehringer Ingelheim Investigational Site
city: Sabadell
country: Spain
facility: 1275.10.34002 Boehringer Ingelheim Investigational Site
city: Tarragona
country: Spain
facility: 1275.10.34005 Boehringer Ingelheim Investigational Site
city: Chernivtsi
country: Ukraine
facility: 1275.10.38006 Boehringer Ingelheim Investigational Site
city: Dnipropetrovs'k
country: Ukraine
facility: 1275.10.38007 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 1275.10.38002 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 1275.10.38003 Boehringer Ingelheim Investigational Site
city: Lviv
country: Ukraine
facility: 1275.10.38004 Boehringer Ingelheim Investigational Site
city: Vinnitsa
country: Ukraine
facility: 1275.10.38001 Boehringer Ingelheim Investigational Site
city: Zhytomyr
country: Ukraine
facility: 1275.10.38005 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.