Clinical trial NCT01012037: Linagliptin 2.5 mg Twice Daily Versus 5 mg Once Daily as add-on Therapy to Twice Daily Metformin in Type 2 Diabetes
Official title: 12 Week Randomised Double-blind BI 1356 2.5 mg Bid vs 5 mg qd add-on to Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-11-11
Enrollment: 491
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 study is to investigate the efficacy and safety of linagliptin 2.5 mg twice daily compared to 5 mg once daily compared to placebo given orally for 12 weeks as add-on therapy to metformin in patients with type 2 diabetes mellitus with insufficient glycaemic control. It is planned to show non-inferiority of linagliptin 2.5 mg twice daily compared to 5 mg once daily and each treatment's superiority over placebo.


Eligibility criteria: Inclusion criteria

1. Diagnosis of type 2 diabetes mellitus.
2. Current treatment with metformin alone (\>/= 1500 mg or maximally tolerated dose) or metformin plus 1 other antidiabetic drug. Metformin must be administered in twice daily dosing regimen. Patients taking metformin three times daily can be included if posology is switched to twice daily and total daily dose is maintained.
3. Glycosylated haemoglobin (HbA1c) is between 7.0% - 10.0%.
4. Body Mass Index (BMI) \</=45 kg/m2.

Exclusion criteria

1. Treatment with extended release metformin.
2. Uncontrolled hyperglycaemia (fasting plasma glucose \> 240 mg/dL or 13.3 mmol/L).
3. Myocardial infarction (MI), stroke or transient ischaemic attack (TIA) within 6 months prior to informed consent.
4. Impaired hepatic or renal function, or gastric bypass surgery.
5. Treatment with glitazones, glucagon like peptide-1 (GLP-1) analogues/mimetics, antiobesity agents, or insulin within 3 months of informed consent.
6. Current treatment with systemic steroids or change in dosage of thyroid hormones.
7. Alcohol or drug abuse within 3 months of informed consent.
8. Participation in another trial with investigational drug within 2 months prior to informed consent.
9. Pre-menopausal women who are nursing, pregnant or not practicing an acceptable method of birth control.

Primary outcomes:
measure: HbA1c Change From Baseline at Week 12
timeFrame: Baseline and week 12
Secondary outcomes:
measure: HbA1c Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis
timeFrame: Baseline and week 6
measure: HbA1c Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis
timeFrame: Baseline and week 12
measure: FPG Change From Baseline at Week 12
timeFrame: Baseline and week 12
measure: FPG Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis
timeFrame: Baseline and week 6
measure: FPG Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis
timeFrame: Baseline and week 12
measure: Percentage of Patients With HbA1c Lowering by 0.5% or More at Week 12
timeFrame: Week 12
measure: Percentage of Patients With Rescue Therapy
timeFrame: 12 weeks
measure: The Occurrence of a Treat to Target Efficacy Response (HbA1c <7.0%) After 12 Weeks of Treatment
timeFrame: 12 weeks
measure: The Occurrence of a Treat to Target Efficacy Response (HbA1c <6.5 %) After 12 Weeks of Treatment
timeFrame: 12 weeks
Other outcomes:
Locations:
city: De Pinte
country: Belgium
facility: 1218.62.32003 Boehringer Ingelheim Investigational Site
city: Kortenaken
country: Belgium
facility: 1218.62.32008 Boehringer Ingelheim Investigational Site
city: Kumtich
country: Belgium
facility: 1218.62.32009 Boehringer Ingelheim Investigational Site
city: Massemen-Wetteren
country: Belgium
facility: 1218.62.32005 Boehringer Ingelheim Investigational Site
city: Natoye
country: Belgium
facility: 1218.62.32004 Boehringer Ingelheim Investigational Site
city: Sint-Job-in't-Goor
country: Belgium
facility: 1218.62.32007 Boehringer Ingelheim Investigational Site
city: Tessenderlo
country: Belgium
facility: 1218.62.32002 Boehringer Ingelheim Investigational Site
city: Wilsele
country: Belgium
facility: 1218.62.32006 Boehringer Ingelheim Investigational Site
city: Calgary
country: Canada
facility: 1218.62.11012 Boehringer Ingelheim Investigational Site
state: Alberta
city: Burnaby
country: Canada
facility: 1218.62.11007 Boehringer Ingelheim Investigational Site
state: British Columbia
city: St. John's
country: Canada
facility: 1218.62.11011 Boehringer Ingelheim Investigational Site
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: 1218.62.11006 Boehringer Ingelheim Investigational Site
state: Nova Scotia
city: Barrie
country: Canada
facility: 1218.62.11001 Boehringer Ingelheim Investigational Site
state: Ontario
city: Brampton
country: Canada
facility: 1218.62.11003 Boehringer Ingelheim Investigational Site
state: Ontario
city: Markham
country: Canada
facility: 1218.62.11004 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: 1218.62.11005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Smiths Falls
country: Canada
facility: 1218.62.11008 Boehringer Ingelheim Investigational Site
state: Ontario
city: Strathroy
country: Canada
facility: 1218.62.11013 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1218.62.11014 Boehringer Ingelheim Investigational Site
state: Ontario
city: Charlottetown
country: Canada
facility: 1218.62.11010 Boehringer Ingelheim Investigational Site
state: Prince Edward Island
city: Montreal
country: Canada
facility: 1218.62.11002 Boehringer Ingelheim Investigational Site
state: Quebec
city: Point Claire
country: Canada
facility: 1218.62.11009 Boehringer Ingelheim Investigational Site
state: Quebec
city: Bort les Orgues
country: France
facility: 1218.62.3303C Boehringer Ingelheim Investigational Site
city: Bourg des cptes
country: France
facility: 1218.62.3306A Boehringer Ingelheim Investigational Site
city: Bugeat
country: France
facility: 1218.62.3303D Boehringer Ingelheim Investigational Site
city: Corsept
country: France
facility: 1218.62.3302H Boehringer Ingelheim Investigational Site
city: Derval
country: France
facility: 1218.62.3308A Boehringer Ingelheim Investigational Site
city: La Chapelle sur Erdre
country: France
facility: 1218.62.3302B Boehringer Ingelheim Investigational Site
city: Levallois Perret
country: France
facility: 1218.62.3304A Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 1218.62.3305A Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 1218.62.3305B Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 1218.62.3305G Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 1218.62.3305H Boehringer Ingelheim Investigational Site
city: Nantes Cedex 1
country: France
facility: 1218.62.3301A Boehringer Ingelheim Investigational Site
city: Nantes
country: France
facility: 1218.62.3302A Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1218.62.3304B Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1218.62.3304D Boehringer Ingelheim Investigational Site
city: Roquevaire
country: France
facility: 1218.62.3305F Boehringer Ingelheim Investigational Site
city: Roquevaire
country: France
facility: 1218.62.3305I Boehringer Ingelheim Investigational Site
city: Rosiers d'Egletons
country: France
facility: 1218.62.3303A Boehringer Ingelheim Investigational Site
city: Sainte Fortunade
country: France
facility: 1218.62.3303H Boehringer Ingelheim Investigational Site
city: Sautron
country: France
facility: 1218.62.3302I Boehringer Ingelheim Investigational Site
city: VUE
country: France
facility: 1218.62.3302G Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1218.62.91001 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1218.62.91004 Boehringer Ingelheim Investigational Site
city: Hyderabad, Andra Pradesh
country: India
facility: 1218.62.91003 Boehringer Ingelheim Investigational Site
city: Nagpru
country: India
facility: 1218.62.91005 Boehringer Ingelheim Investigational Site
city: Trivandrum
country: India
facility: 1218.62.91002 Boehringer Ingelheim Investigational Site
city: Ancona
country: Italy
facility: 1218.62.39010 Boehringer Ingelheim Investigational Site
city: Catania
country: Italy
facility: 1218.62.39006 Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: 1218.62.39004 Boehringer Ingelheim Investigational Site
city: Gissi (CH)
country: Italy
facility: 1218.62.39009 Boehringer Ingelheim Investigational Site
city: Palermo
country: Italy
facility: 1218.62.39003 Boehringer Ingelheim Investigational Site
city: Pisa
country: Italy
facility: 1218.62.39001 Boehringer Ingelheim Investigational Site
city: Pordenone
country: Italy
facility: 1218.62.39002 Boehringer Ingelheim Investigational Site
city: Ravenna
country: Italy
facility: 1218.62.39012 Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: 1218.62.39007 Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: 1218.62.39011 Boehringer Ingelheim Investigational Site
city: Goyang
country: Korea, Republic of
facility: 1218.62.82005 Boehringer Ingelheim Investigational Site
city: Goyang
country: Korea, Republic of
facility: 1218.62.82006 Boehringer Ingelheim Investigational Site
city: Incheon
country: Korea, Republic of
facility: 1218.62.82003 Boehringer Ingelheim Investigational Site
city: Pucheon
country: Korea, Republic of
facility: 1218.62.82004 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1218.62.82002 Boehringer Ingelheim Investigational Site
city: Suwon
country: Korea, Republic of
facility: 1218.62.82001 Boehringer Ingelheim Investigational Site
city: Kelantan Kota Bahru
country: Malaysia
facility: 1218.62.60001 Boehringer Ingelheim Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: 1218.62.60005 Boehringer Ingelheim Investigational Site
city: Penang
country: Malaysia
facility: 1218.62.60002 Boehringer Ingelheim Investigational Site
city: Putrajaya
country: Malaysia
facility: 1218.62.60003 Boehringer Ingelheim Investigational Site
city: Seremban
country: Malaysia
facility: 1218.62.60004 Boehringer Ingelheim Investigational Site
city: Almere
country: Netherlands
facility: 1218.62.31007 Boehringer Ingelheim Investigational Site
city: Breezerveld
country: Netherlands
facility: 1218.62.31004 Boehringer Ingelheim Investigational Site
city: Etten-Leur
country: Netherlands
facility: 1218.62.31005 Boehringer Ingelheim Investigational Site
city: Lieshout
country: Netherlands
facility: 1218.62.31002 Boehringer Ingelheim Investigational Site
city: Oude Pekela
country: Netherlands
facility: 1218.62.31001 Boehringer Ingelheim Investigational Site
city: Voerendaal
country: Netherlands
facility: 1218.62.31008 Boehringer Ingelheim Investigational Site
city: Wildervank
country: Netherlands
facility: 1218.62.31009 Boehringer Ingelheim Investigational Site
city: Woerden
country: Netherlands
facility: 1218.62.31003 Boehringer Ingelheim Investigational Site
city: Badia del Vallés (Barcelona)
country: Spain
facility: 1218.62.34003 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat (Barcelona)
country: Spain
facility: 1218.62.34002 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1218.62.34005 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1218.62.34006 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1218.62.34007 Boehringer Ingelheim Investigational Site
city: Palma (Mallorca)
country: Spain
facility: 1218.62.34001 Boehringer Ingelheim Investigational Site
city: Palma de Mallorca
country: Spain
facility: 1218.62.34008 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Ross SA, Rafeiro E, Meinicke T, Toorawa R, Weber-Born S, Woerle HJ. Efficacy and safety of linagliptin 2.5 mg twice daily versus 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, placebo-controlled trial. Curr Med Res Opin. 2012 Sep;28(9):1465-74. doi: 10.1185/03007995.2012.714360. Epub 2012 Aug 13.