Clinical trial NCT00798161: Safety and Efficacy of Linagliptin (BI 1356) Plus Metformin in Type 2 Diabetes, Factorial Design
Official title: A Phase III Randomised, Double-blind, Placebo-controlled Parallel Group Study to Compare the Efficacy and Safety of Twice Daily Administration of the Free Combination of BI 1356 2.5 mg + Metformin 500 mg, or of BI 1356 2.5 mg + Metformin 1000 mg, With the Individual Components of Metformin (500 mg or 1000 mg Twice Daily), and BI 1356 (5.0 mg Once Daily) Over 24 Weeks in Drug Naive or Previously Treated (4 Weeks Wash-out and 2 Weeks Placebo run-in) Type 2 Diabetic Patients With Insufficient Glycaemic Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-11-25
Enrollment: 857
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the randomised part of the study is to investigate the efficacy and safety of BI 1356 plus metformin compared to BI 1356 or metformin alone given for 24 weeks to drug naive or previously treated (4 weeks wash-out, 2 weeks placebo run-in) type 2 diabetic patients with insufficient glycaemic control. For the open-label part of the study the objective is to estimate the efficacy and safety of BI 1356 and metformin in type 2 diabetic patients with very poor glycaemic control for 24 weeks


Eligibility criteria: Inclusion criteria:

Patients with type 2 diabetes (drug naive or pre-treated) with insufficient glycaemic control (HbA1c higher or equal than 7.5 to less than 11.0 %), with very poor glycaemic control (HbA1c higher or equal than 11.0 %) who are not eligible for randomisation to be included in the open-label arm

Exclusion criteria:

Myocardial infarction, stroke or transient ischemic attack (TIA), unstable or acute congestive heart failure, impaired hepatic function, treatment with rosiglitazone or pioglitazone, with a GLP1 analogue, with insulin, with anti-obesity drugs, with systemic steroids, renal failure or impairment, gastric bypass

Primary outcomes:
measure: HbA1c Change From Baseline at Week 24
timeFrame: Baseline and week 24
Secondary outcomes:
measure: HbA1c Change From Baseline at Week 6
timeFrame: Baseline and week 6
measure: HbA1c Change From Baseline at Week 12
timeFrame: Baseline and week 12
measure: HbA1c Change From Baseline at Week 18
timeFrame: Baseline and week 18
measure: FPG Change From Baseline at Week 24
timeFrame: Baseline and week 24
measure: FPG Change From Baseline at Week 2
timeFrame: Baseline and week 2
measure: FPG Change From Baseline at Week 6
timeFrame: Baseline and week 6
measure: FPG Change From Baseline at Week 12
timeFrame: Baseline and week 12
measure: FPG Change From Baseline at Week 18
timeFrame: Baseline and week 18
measure: Percentage of Patients With HbA1c <7.0% at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Patients With HbA1c<7.0 at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Patients With HbA1c <6.5% at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Patients With HbA1c < 6.5% at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Patients With HbA1c Lowering by 0.5% at Week 24
timeFrame: Baseline and week 24
measure: Adjusted Means for 2h Post-Prandial Glucose (PPG) Change From Baseline at Week 24
timeFrame: Baseline and week 24
measure: HbA1c Change From Baseline at Week 24 for Open-label Patients
timeFrame: Baseline and week 24
measure: FPG Change From Baseline at Week 24 for Open-label Patients
timeFrame: Baseline and week 24
measure: Use of Rescue Therapy
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: 1218.46.11005 Boehringer Ingelheim Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: 1218.46.11003 Boehringer Ingelheim Investigational Site
state: Alberta
city: Red Deer
country: Canada
facility: 1218.46.11002 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 1218.46.11006 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: 1218.46.11008 Boehringer Ingelheim Investigational Site
state: Manitoba
city: Hamilton
country: Canada
facility: 1218.46.11004 Boehringer Ingelheim Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: 1218.46.11007 Boehringer Ingelheim Investigational Site
state: Ontario
city: Oshawa
country: Canada
facility: 1218.46.11009 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1218.46.11010 Boehringer Ingelheim Investigational Site
state: Ontario
city: Karlovac
country: Croatia
facility: 1218.46.38502 Boehringer Ingelheim Investigational Site
city: Krapinske Toplice
country: Croatia
facility: 1218.46.38503 Boehringer Ingelheim Investigational Site
city: Osijek
country: Croatia
facility: 1218.46.38504 Boehringer Ingelheim Investigational Site
city: Rijeka
country: Croatia
facility: 1218.46.38505 Boehringer Ingelheim Investigational Site
city: Sisak
country: Croatia
facility: 1218.46.38501 Boehringer Ingelheim Investigational Site
city: Zagreb
country: Croatia
facility: 1218.46.38506 Boehringer Ingelheim Investigational Site
city: Pärnu
country: Estonia
facility: 1218.46.37202 Boehringer Ingelheim Investigational Site
city: Tallin
country: Estonia
facility: 1218.46.37201 Boehringer Ingelheim Investigational Site
city: Tallin
country: Estonia
facility: 1218.46.37203 Boehringer Ingelheim Investigational Site
city: Aire sur l'Aadour
country: France
facility: 1218.46.3303D Boehringer Ingelheim Investigational Site
city: Bischheim
country: France
facility: 1218.46.3308B Boehringer Ingelheim Investigational Site
city: Bourges
country: France
facility: 1218.46.3305A Boehringer Ingelheim Investigational Site
city: Bousse
country: France
facility: 1218.46.3304F Boehringer Ingelheim Investigational Site
city: Carresse Cassaber
country: France
facility: 1218.46.3306D Boehringer Ingelheim Investigational Site
city: Gambsheim
country: France
facility: 1218.46.3308C Boehringer Ingelheim Investigational Site
city: Garchizy
country: France
facility: 1218.46.3305D Boehringer Ingelheim Investigational Site
city: Grenoble cédex
country: France
facility: 1218.46.3301A Boehringer Ingelheim Investigational Site
city: Guerigny
country: France
facility: 1218.46.3305B Boehringer Ingelheim Investigational Site
city: Jarny
country: France
facility: 1218.46.3304A Boehringer Ingelheim Investigational Site
city: La Riche
country: France
facility: 1218.46.3302D Boehringer Ingelheim Investigational Site
city: La Seyne sur Mer
country: France
facility: 1218.46.3307A Boehringer Ingelheim Investigational Site
city: La Seyne sur Mer
country: France
facility: 1218.46.3307E Boehringer Ingelheim Investigational Site
city: Lury
country: France
facility: 1218.46.3305G Boehringer Ingelheim Investigational Site
city: Mars la Tour
country: France
facility: 1218.46.3304D Boehringer Ingelheim Investigational Site
city: Mondelange
country: France
facility: 1218.46.3304B Boehringer Ingelheim Investigational Site
city: Mont de Marsan
country: France
facility: 1218.46.3303A Boehringer Ingelheim Investigational Site
city: Mont de Marsan
country: France
facility: 1218.46.3303C Boehringer Ingelheim Investigational Site
city: Mont de Marsan
country: France
facility: 1218.46.3303E Boehringer Ingelheim Investigational Site
city: Moutiers
country: France
facility: 1218.46.3304C Boehringer Ingelheim Investigational Site
city: Mundolsheim
country: France
facility: 1218.46.3308F Boehringer Ingelheim Investigational Site
city: Nevers
country: France
facility: 1218.46.3305C Boehringer Ingelheim Investigational Site
city: Nevers
country: France
facility: 1218.46.3305E Boehringer Ingelheim Investigational Site
city: Ortez
country: France
facility: 1218.46.3306A Boehringer Ingelheim Investigational Site
city: Orthez
country: France
facility: 1218.46.3306C Boehringer Ingelheim Investigational Site
city: Orthez
country: France
facility: 1218.46.3306E Boehringer Ingelheim Investigational Site
city: Orthez
country: France
facility: 1218.46.3306F Boehringer Ingelheim Investigational Site
city: Pont à Mousson
country: France
facility: 1218.46.3304E Boehringer Ingelheim Investigational Site
city: Saint Avertin
country: France
facility: 1218.46.3302B Boehringer Ingelheim Investigational Site
city: Saint Avertin
country: France
facility: 1218.46.3302C Boehringer Ingelheim Investigational Site
city: Salies de Bearn
country: France
facility: 1218.46.3306B Boehringer Ingelheim Investigational Site
city: Savonnières
country: France
facility: 1218.46.3302E Boehringer Ingelheim Investigational Site
city: St Martin d'Oney
country: France
facility: 1218.46.3303B Boehringer Ingelheim Investigational Site
city: Strasbourg
country: France
facility: 1218.46.3308A Boehringer Ingelheim Investigational Site
city: Strasbourg
country: France
facility: 1218.46.3308D Boehringer Ingelheim Investigational Site
city: Strasbourg
country: France
facility: 1218.46.3308E Boehringer Ingelheim Investigational Site
city: Toulon
country: France
facility: 1218.46.3307B Boehringer Ingelheim Investigational Site
city: Toulon
country: France
facility: 1218.46.3307C Boehringer Ingelheim Investigational Site
city: Toulon
country: France
facility: 1218.46.3307D Boehringer Ingelheim Investigational Site
city: Tours
country: France
facility: 1218.46.3302A Boehringer Ingelheim Investigational Site
city: Vandoeuvre les Nancy
country: France
facility: 1218.46.3304H Boehringer Ingelheim Investigational Site
city: Bad Dürrheim-Sunthausen
country: Germany
facility: 1218.46.49002 Boehringer Ingelheim Investigational Site
city: Bad Mergentheim
country: Germany
facility: 1218.46.49001 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 1218.46.49006 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1218.46.49003 Boehringer Ingelheim Investigational Site
city: Neuwied
country: Germany
facility: 1218.46.49008 Boehringer Ingelheim Investigational Site
city: Schauenburg
country: Germany
facility: 1218.46.49007 Boehringer Ingelheim Investigational Site
city: Aurangabad
country: India
facility: 1218.46.91009 Boehringer Ingelheim Investigational Site
city: Babgalore
country: India
facility: 1218.46.91007 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1218.46.91001 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1218.46.91004 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1218.46.91012 Boehringer Ingelheim Investigational Site
city: Bhopal
country: India
facility: 1218.46.91011 Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: 1218.46.91003 Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: 1218.46.91020 Boehringer Ingelheim Investigational Site
city: Hyderadad
country: India
facility: 1218.46.91018 Boehringer Ingelheim Investigational Site
city: Jaipur
country: India
facility: 1218.46.91008 Boehringer Ingelheim Investigational Site
city: Madurai
country: India
facility: 1218.46.91019 Boehringer Ingelheim Investigational Site
city: Maharashtra
country: India
facility: 1218.46.91013 Boehringer Ingelheim Investigational Site
city: Manipal
country: India
facility: 1218.46.91002 Boehringer Ingelheim Investigational Site
city: Mumbai
country: India
facility: 1218.46.91015 Boehringer Ingelheim Investigational Site
city: Nagpur
country: India
facility: 1218.46.91014 Boehringer Ingelheim Investigational Site
city: New Delhi
country: India
facility: 1218.46.91017 Boehringer Ingelheim Investigational Site
city: P.O Trivandrum
country: India
facility: 1218.46.91016 Boehringer Ingelheim Investigational Site
city: Pune
country: India
facility: 1218.46.91010 Boehringer Ingelheim Investigational Site
city: West Bengal
country: India
facility: 1218.46.91006 Boehringer Ingelheim Investigational Site
city: Kaunas
country: Lithuania
facility: 1218.46.37001 Boehringer Ingelheim Investigational Site
city: Kaunas
country: Lithuania
facility: 1218.46.37004 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 1218.46.37003 Boehringer Ingelheim Investigational Site
city: Aguascalientes
country: Mexico
facility: 1218.46.52006 Boehringer Ingelheim Investigational Site
city: Cuernavaca
country: Mexico
facility: 1218.46.52002 Boehringer Ingelheim Investigational Site
city: Guadalajara
country: Mexico
facility: 1218.46.52003 Boehringer Ingelheim Investigational Site
city: Guadalajara
country: Mexico
facility: 1218.46.52004 Boehringer Ingelheim Investigational Site
city: Mexico
country: Mexico
facility: 1218.46.52007 Boehringer Ingelheim Investigational Site
city: Mexico
country: Mexico
facility: 1218.46.52008 Boehringer Ingelheim Investigational Site
city: Pachuca
country: Mexico
facility: 1218.46.52001 Boehringer Ingelheim Investigational Site
city: Tijuana
country: Mexico
facility: 1218.46.52010 Boehringer Ingelheim Investigational Site
city: Veracruz
country: Mexico
facility: 1218.46.52009 Boehringer Ingelheim Investigational Site
city: 's Hertogenbosch
country: Netherlands
facility: 1218.46.31004 Boehringer Ingelheim Investigational Site
city: 's Hertogenbosch
country: Netherlands
facility: 1218.46.31005 Boehringer Ingelheim Investigational Site
city: Almere
country: Netherlands
facility: 1218.46.31001 Boehringer Ingelheim Investigational Site
city: Beek en Donk
country: Netherlands
facility: 1218.46.31002 Boehringer Ingelheim Investigational Site
city: Beek
country: Netherlands
facility: 1218.46.31008 Boehringer Ingelheim Investigational Site
city: Breda
country: Netherlands
facility: 1218.46.31010 Boehringer Ingelheim Investigational Site
city: Eindhoven
country: Netherlands
facility: 1218.46.31011 Boehringer Ingelheim Investigational Site
city: Groningen
country: Netherlands
facility: 1218.46.31013 Boehringer Ingelheim Investigational Site
city: Leiderdrop
country: Netherlands
facility: 1218.46.31012 Boehringer Ingelheim Investigational Site
city: Nijmegen
country: Netherlands
facility: 1218.46.31016 Boehringer Ingelheim Investigational Site
city: Rotterdam
country: Netherlands
facility: 1218.46.31009 Boehringer Ingelheim Investigational Site
city: Velp
country: Netherlands
facility: 1218.46.31014 Boehringer Ingelheim Investigational Site
city: Zoetermeer
country: Netherlands
facility: 1218.46.31015 Boehringer Ingelheim Investigational Site
city: Alba Iulia
country: Romania
facility: 1218.46.40001 Boehringer Ingelheim Investigational Site
city: Galati
country: Romania
facility: 1218.46.40005 Boehringer Ingelheim Investigational Site
city: Oradea
country: Romania
facility: 1218.46.40003 Boehringer Ingelheim Investigational Site
city: Ploiesti
country: Romania
facility: 1218.46.40002 Boehringer Ingelheim Investigational Site
city: Satu Mare
country: Romania
facility: 1218.46.40004 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.46.70001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.46.70002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.46.70003 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.46.70004 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.46.70006 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.46.70008 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1218.46.70005 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1218.46.70007 Boehringer Ingelheim Investigational Site
city: Goteborg
country: Sweden
facility: 1218.46.46002 Boehringer Ingelheim Investigational Site
city: Goteborg
country: Sweden
facility: 1218.46.46004 Boehringer Ingelheim Investigational Site
city: Malmo
country: Sweden
facility: 1218.46.46003 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 1218.46.46005 Boehringer Ingelheim Investigational Site
city: Uppsala
country: Sweden
facility: 1218.46.46001 Boehringer Ingelheim Investigational Site
city: Bab Sâadoun Tunis
country: Tunisia
facility: 1218.46.2162A Boehringer Ingelheim Investigational Site
city: Tunis
country: Tunisia
facility: 1218.46.2161A Boehringer Ingelheim Investigational Site
city: Tunis
country: Tunisia
facility: 1218.46.2161B Boehringer Ingelheim Investigational Site
city: Tunis
country: Tunisia
facility: 1218.46.2163A Boehringer Ingelheim Investigational Site
city: Tunis
country: Tunisia
facility: 1218.46.2163B Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 1218.46.38003 Boehringer Ingelheim Investigational Site
city: Lviv
country: Ukraine
facility: 1218.46.38001 Boehringer Ingelheim Investigational Site
city: Lvov
country: Ukraine
facility: 1218.46.38005 Boehringer Ingelheim Investigational Site
city: Odesa
country: Ukraine
facility: 1218.46.38004 Boehringer Ingelheim Investigational Site
city: Odessa
country: Ukraine
facility: 1218.46.38002 Boehringer Ingelheim Investigational Site
city: Vinnitsa
country: Ukraine
facility: 1218.46.38006 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Lv Q, Shen J, Miao L, Ye B, Schepers C, Plat A, Shi Y. Early Combination Therapy with Linagliptin and Metformin in People with Type 2 Diabetes Improves Glycemic Control to HbA1c </= 6.5% without Increasing Hypoglycemia: Pooled Analysis of Two Randomized Clinical Trials. Diabetes Ther. 2020 Jun;11(6):1317-1330. doi: 10.1007/s13300-020-00819-9. Epub 2020 Apr 23.