Treatment of Type 2 Diabetes With Linagliptin 2.5 mg Bid + Metformin 500 or 1000 mg Bid and Metformin 1000 mg Bid

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00915772
First received: June 2, 2009
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

A phase III randomised, double-blind parallel group extension study to investigate the efficacy and safety of twice daily administration of the free combination of linagliptin 2.5 mg + metformin 500 mg or of linagliptin 2.5 mg + metformin 1000 mg versus monotherapy with metformin 1000 mg twice daily over 54 weeks in type 2 diabetic patients previously completing the double-blind part of study 1218.46


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Linagliptin + metformin
Drug: Linagliptin+metformin
Drug: Metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Extension Study Linagliptin 2.5 mg Bid + Metformin 500 or 1000 mg Bid Versus Metformin 1000 mg Bid

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Frequency of Patients With Adverse Events (AEs) [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
    This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures.

  • Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
    Baseline is defined as Visit 1 of 1218.52.

  • Change From Baseline at Week 54 in Pulse Rate [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
    Baseline is defined as Visit 1 of 1218.52.

  • Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
  • Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
    ULN means upper limit of normal

  • Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE [ Time Frame: Baseline and drug stop (up to 54 weeks) + 7 days ] [ Designated as safety issue: No ]
    Frequency of patients with adverse events by treatment, primary system organ class and preferred term


Secondary Outcome Measures:
  • Change in HbA1c From Baseline Over Time [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. Thus, this change from baseline reflects the visit HbA1c percent minus the baseline HbA1c percent. Baseline is defined as visit 1 of 1218.52.

  • Number of Patients With HbA1c <7.0% After 54 Weeks [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
  • Number of Patients With HbA1c <6.5% Over Time [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
  • Number of Patients With HbA1c of at Least <0.5% Over Time [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
  • Change in FPG From Baseline Over Time [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
    Baseline is defined as visit 1 of 1218.52.

  • Number of Patients With Rescue Therapy [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
  • Change in HbA1c From Baseline Over Time [ Time Frame: 78 weeks ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. Thus, this change from baseline reflects the visit HbA1c percent minus the baseline HbA1c percent. Baseline is defined as visit 3 from study 1218.46 (NCT00915772).


Enrollment: 567
Study Start Date: June 2009
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Linagliptin + metformin bid
Linagliptin low dose + metformin 500 mg, bid
Drug: Linagliptin + metformin
Linagliptin tablet low dose + metformin tablet 500 mg bid
Experimental: Linagliptin+ metformin bid
Linagliptin low dose + metformin 1000 mg bid
Drug: Linagliptin+metformin
Linagliptin low dose tablet + metformin 1000 mg tablet bid
Active Comparator: Metformin bid
Metformin 1000 mg bid
Drug: Metformin
Metformin 1000 mg tablet bid

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Signed and dated written informed consent, at the latest by the date of Visit 1
  • Patients completing the entire treatment period of the double-blind study 1218.46, who are not treated with rescue medication (Visit 7)

Exclusion criteria:

  • Patients who meet one or more of the withdrawal criteria of the treatment period of the previous study 1218.46
  • Pre-menopausal women (last menstruation equal or less than 1 year prior to signing informed consent) who:
  • are nursing or pregnant,
  • or are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner and in addition for male partners a barrier method, such as the use of condom with spermicide. No exception will be made.
  • Alcohol abuse within the 3 months prior to informed consent that would interfere with study participation
  • Drug abuse that in the opinion of the investigator would interfere with trial participation
  • Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of the study medication
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00915772

  Hide Study Locations
Locations
Canada, Alberta
1218.52.11005 Boehringer Ingelheim Investigational Site
Calgary, Alberta, Canada
1218.52.11003 Boehringer Ingelheim Investigational Site
Edmonton, Alberta, Canada
1218.52.11002 Boehringer Ingelheim Investigational Site
Red Deer, Alberta, Canada
Canada, British Columbia
1218.52.11006 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
Canada, Manitoba
1218.52.11008 Boehringer Ingelheim Investigational Site
Winnipeg, Manitoba, Canada
Canada, Ontario
1218.52.11004 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
1218.52.11007 Boehringer Ingelheim Investigational Site
Oakville, Ontario, Canada
1218.52.11010 Boehringer Ingelheim Investigational Site
Toronto, Ontario, Canada
Croatia
1218.52.38502 Boehringer Ingelheim Investigational Site
Karlovac, Croatia
1218.52.38503 Boehringer Ingelheim Investigational Site
Krapinske Toplice, Croatia
1218.52.38504 Boehringer Ingelheim Investigational Site
Osijek, Croatia
1218.52.38505 Boehringer Ingelheim Investigational Site
Rijeka, Croatia
1218.52.38501 Boehringer Ingelheim Investigational Site
Sisak, Croatia
Estonia
1218.52.37202 Boehringer Ingelheim Investigational Site
Pärnu, Estonia
1218.52.37203 Boehringer Ingelheim Investigational Site
Tallin, Estonia
1218.52.37201 Boehringer Ingelheim Investigational Site
Tallin, Estonia
France
1218.52.3303D Boehringer Ingelheim Investigational Site
Aire sur l'Aadour, France
1218.52.3308B Boehringer Ingelheim Investigational Site
Bischheim, France
1218.52.3305A Boehringer Ingelheim Investigational Site
Bourges, France
1218.52.3304F Boehringer Ingelheim Investigational Site
Bousse, France
1218.52.3308C Boehringer Ingelheim Investigational Site
Gambsheim, France
1218.52.3301A Boehringer Ingelheim Investigational Site
Grenoble cédex, France
1218.52.3305B Boehringer Ingelheim Investigational Site
Guerigny, France
1218.52.3304A Boehringer Ingelheim Investigational Site
Jarny, France
1218.52.3302D Boehringer Ingelheim Investigational Site
La Riche, France
1218.52.9999 Boehringer Ingelheim Investigational Site
La Riche, France
1218.52.3307E Boehringer Ingelheim Investigational Site
La Seyne sur Mer, France
1218.52.3307A Boehringer Ingelheim Investigational Site
La Seyne sur Mer, France
1218.52.3305G Boehringer Ingelheim Investigational Site
Lury, France
1218.52.3303A Boehringer Ingelheim Investigational Site
Mont de Marsan, France
1218.52.3308F Boehringer Ingelheim Investigational Site
Mundolsheim, France
1218.52.3305E Boehringer Ingelheim Investigational Site
Nevers, France
1218.52.3306A Boehringer Ingelheim Investigational Site
Ortez, France
1218.52.3306C Boehringer Ingelheim Investigational Site
Orthez, France
1218.52.3302E Boehringer Ingelheim Investigational Site
Savonnières, France
1218.52.3303B Boehringer Ingelheim Investigational Site
St Martin d'Oney, France
1218.52.3308D Boehringer Ingelheim Investigational Site
Strasbourg, France
1218.52.3308E Boehringer Ingelheim Investigational Site
Strasbourg, France
1218.52.3308A Boehringer Ingelheim Investigational Site
Strasbourg, France
1218.52.3307D Boehringer Ingelheim Investigational Site
Toulon, France
1218.52.3302A Boehringer Ingelheim Investigational Site
Tours, France
Germany
1218.52.49002 Boehringer Ingelheim Investigational Site
Bad Dürrheim-Sunthausen, Germany
1218.52.49006 Boehringer Ingelheim Investigational Site
Köln, Germany
1218.52.49003 Boehringer Ingelheim Investigational Site
München, Germany
1218.52.49007 Boehringer Ingelheim Investigational Site
Schauenburg, Germany
India
1218.52.91009 Boehringer Ingelheim Investigational Site
Aurangabad, India
1218.52.91004 Boehringer Ingelheim Investigational Site
Bangalore, India
1218.52.91012 Boehringer Ingelheim Investigational Site
Bangalore, India
1218.52.91001 Boehringer Ingelheim Investigational Site
Bangalore, India
1218.52.91011 Boehringer Ingelheim Investigational Site
Bhopal, India
1218.52.91003 Boehringer Ingelheim Investigational Site
Chennai, India
1218.52.91020 Boehringer Ingelheim Investigational Site
Chennai, India
1218.52.91018 Boehringer Ingelheim Investigational Site
Hyderadad, India
1218.52.91008 Boehringer Ingelheim Investigational Site
Jaipur, India
1218.52.91002 Boehringer Ingelheim Investigational Site
Karnataka, India
1218.52.91007 Boehringer Ingelheim Investigational Site
Karnataka, India
1218.52.91019 Boehringer Ingelheim Investigational Site
Madurai, India
1218.52.91013 Boehringer Ingelheim Investigational Site
Maharashtra, India
1218.52.91015 Boehringer Ingelheim Investigational Site
Mumbai, India
1218.52.91014 Boehringer Ingelheim Investigational Site
Nagpru, India
1218.52.91016 Boehringer Ingelheim Investigational Site
P.O.Trivandrum, India
1218.52.91010 Boehringer Ingelheim Investigational Site
Pune, India
1218.52.91006 Boehringer Ingelheim Investigational Site
West Bengal, India
Lithuania
1218.52.37004 Boehringer Ingelheim Investigational Site
Kaunas, Lithuania
1218.52.37001 Boehringer Ingelheim Investigational Site
Kaunas, Lithuania
1218.52.37003 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
Mexico
1218.52.52006 Boehringer Ingelheim Investigational Site
Aguascalientes, Mexico
1218.52.52002 Boehringer Ingelheim Investigational Site
Cuernavaca, Mexico
1218.52.52004 Boehringer Ingelheim Investigational Site
Guadalajara, Mexico
1218.52.52007 Boehringer Ingelheim Investigational Site
Mexico, Mexico
1218.52.52008 Boehringer Ingelheim Investigational Site
Mexico, Mexico
1218.52.52010 Boehringer Ingelheim Investigational Site
Tijuana, Mexico
1218.52.52009 Boehringer Ingelheim Investigational Site
Veracruz, Mexico
Netherlands
1218.52.31005 Boehringer Ingelheim Investigational Site
's Hertogenbosch, Netherlands
1218.52.31004 Boehringer Ingelheim Investigational Site
's Hertogenbosch, Netherlands
1218.52.31001 Boehringer Ingelheim Investigational Site
Almere, Netherlands
1218.52.31002 Boehringer Ingelheim Investigational Site
Beek en Donk, Netherlands
1218.52.31010 Boehringer Ingelheim Investigational Site
Breda, Netherlands
1218.52.31013 Boehringer Ingelheim Investigational Site
Groningen, Netherlands
1218.52.31014 Boehringer Ingelheim Investigational Site
Velp, Netherlands
1218.52.31015 Boehringer Ingelheim Investigational Site
Zoetermeer, Netherlands
Romania
1218.52.40001 Boehringer Ingelheim Investigational Site
Alba Iulia, Romania
1218.52.40005 Boehringer Ingelheim Investigational Site
Galati, Romania
1218.52.40003 Boehringer Ingelheim Investigational Site
Oradea, Romania
1218.52.40002 Boehringer Ingelheim Investigational Site
Ploiesti, Romania
1218.52.40004 Boehringer Ingelheim Investigational Site
Satu Mare, Romania
Russian Federation
1218.52.70004 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1218.52.70006 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1218.52.70002 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1218.52.70001 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1218.52.70003 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1218.52.70005 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
1218.52.70007 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
Sweden
1218.52.46002 Boehringer Ingelheim Investigational Site
Goteborg, Sweden
1218.52.46003 Boehringer Ingelheim Investigational Site
Malmo, Sweden
1218.52.46005 Boehringer Ingelheim Investigational Site
Stockholm, Sweden
1218.52.46001 Boehringer Ingelheim Investigational Site
Uppsala, Sweden
Tunisia
1218.52.2162A Boehringer Ingelheim Investigational Site
Bab Saâdoun Tunis, Tunisia
1218.52.9992 Boehringer Ingelheim Investigational Site
Bab Sâadoun Tunis, Tunisia
1218.52.2162B Boehringer Ingelheim Investigational Site
Bab Sâadoun Tunis, Tunisia
1218.52.2161B Boehringer Ingelheim Investigational Site
Tunis, Tunisia
1218.52.2163B Boehringer Ingelheim Investigational Site
Tunis, Tunisia
1218.52.2161A Boehringer Ingelheim Investigational Site
Tunis, Tunisia
1218.52.9991 Boehringer Ingelheim Investigational Site
Tunis, Tunisia
1218.52.2163A Boehringer Ingelheim Investigational Site
Tunis, Tunisia
1218.52.9993 Boehringer Ingelheim Investigational Site
Tunis, Tunisia
Ukraine
1218.52.38003 Boehringer Ingelheim Investigational Site
Kiev, Ukraine
1218.52.38001 Boehringer Ingelheim Investigational Site
Lviv, Ukraine
1218.52.38005 Boehringer Ingelheim Investigational Site
Lvov, Ukraine
1218.52.38004 Boehringer Ingelheim Investigational Site
Odessa, Ukraine
1218.52.38002 Boehringer Ingelheim Investigational Site
Odessa, Ukraine
1218.52.38006 Boehringer Ingelheim Investigational Site
Vinnitsa, Ukraine
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00915772     History of Changes
Other Study ID Numbers: 1218.52, 2008-008494-59
Study First Received: June 2, 2009
Results First Received: June 13, 2012
Last Updated: December 11, 2013
Health Authority: Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Estonia: The State Agency of Medicine
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
India: Drugs Controller General of India
Lithuania: State Medicine Control Agency - Ministry of Health
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Central Committee Research Involving Human Subjects
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Sweden: Regional Ethical Review Board
Tunisia: Ministry of Public Health
Ukraine: State Pharmacological Center - Ministry of Health

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
BI 1356
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 21, 2014