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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Extension Study Linagliptin 2.5 mg Bid + Metformin 500 or 1000 mg Bid Versus Metformin 1000 mg Bid

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00915772
• Other study ID #: 1218.52
• Secondary ID: 2008-008494-59
• Status: Completed
• Phase: Phase 3
• First received: June 2, 2009
• Last updated: April 29, 2014
• Start date: June 2009

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaCroatia: Agency for Medicinal Product and Medical DevicesEstonia: The State Agency of MedicineFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesIndia: Drugs Controller General of IndiaLithuania: State Medicine Control Agency - Ministry of HealthMexico: Federal Commission for Sanitary Risks ProtectionNetherlands: Central Committee Research Involving Human SubjectsRomania: National Medicines AgencyRussia: Pharmacological Committee, Ministry of HealthSweden: Regional Ethical Review BoardTunisia: Ministry of Public HealthUkraine: State Pharmacological Center - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 567
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Linagliptin + metformin
Linagliptin tablet low dose + metformin tablet 500 mg bid
• Linagliptin+metformin
Linagliptin low dose tablet + metformin 1000 mg tablet bid
• Metformin
Metformin 1000 mg tablet bid

Locations

Country	Name	City	State
Canada	1218.52.11005 Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	1218.52.11003 Boehringer Ingelheim Investigational Site	Edmonton	Alberta
Canada	1218.52.11004 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1218.52.11007 Boehringer Ingelheim Investigational Site	Oakville	Ontario
Canada	1218.52.11002 Boehringer Ingelheim Investigational Site	Red Deer	Alberta
Canada	1218.52.11010 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1218.52.11006 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	1218.52.11008 Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba
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
Estonia	1218.52.37202 Boehringer Ingelheim Investigational Site	Pärnu
Estonia	1218.52.37201 Boehringer Ingelheim Investigational Site	Tallin
Estonia	1218.52.37203 Boehringer Ingelheim Investigational Site	Tallin
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	1218.52.3307A Boehringer Ingelheim Investigational Site	La Seyne sur Mer
France	1218.52.3307E 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	1218.52.3308A Boehringer Ingelheim Investigational Site	Strasbourg
France	1218.52.3308D Boehringer Ingelheim Investigational Site	Strasbourg
France	1218.52.3308E Boehringer Ingelheim Investigational Site	Strasbourg
France	1218.52.3307D Boehringer Ingelheim Investigational Site	Toulon
France	1218.52.3302A Boehringer Ingelheim Investigational Site	Tours
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
India	1218.52.91009 Boehringer Ingelheim Investigational Site	Aurangabad
India	1218.52.91001 Boehringer Ingelheim Investigational Site	Bangalore
India	1218.52.91004 Boehringer Ingelheim Investigational Site	Bangalore
India	1218.52.91012 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
Lithuania	1218.52.37001 Boehringer Ingelheim Investigational Site	Kaunas
Lithuania	1218.52.37004 Boehringer Ingelheim Investigational Site	Kaunas
Lithuania	1218.52.37003 Boehringer Ingelheim Investigational Site	Vilnius
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
Netherlands	1218.52.31004 Boehringer Ingelheim Investigational Site	's Hertogenbosch
Netherlands	1218.52.31005 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
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
Russian Federation	1218.52.70001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1218.52.70002 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1218.52.70003 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1218.52.70004 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1218.52.70006 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
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
Tunisia	1218.52.2162A Boehringer Ingelheim Investigational Site	Bab Saâdoun Tunis
Tunisia	1218.52.2162B Boehringer Ingelheim Investigational Site	Bab Sâadoun Tunis
Tunisia	1218.52.9992 Boehringer Ingelheim Investigational Site	Bab Sâadoun Tunis
Tunisia	1218.52.2161A Boehringer Ingelheim Investigational Site	Tunis
Tunisia	1218.52.2161B Boehringer Ingelheim Investigational Site	Tunis
Tunisia	1218.52.2163A Boehringer Ingelheim Investigational Site	Tunis
Tunisia	1218.52.2163B Boehringer Ingelheim Investigational Site	Tunis
Tunisia	1218.52.9991 Boehringer Ingelheim Investigational Site	Tunis
Tunisia	1218.52.9993 Boehringer Ingelheim Investigational Site	Tunis
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	1218.52.38002 Boehringer Ingelheim Investigational Site	Odessa
Ukraine	1218.52.38004 Boehringer Ingelheim Investigational Site	Odessa
Ukraine	1218.52.38006 Boehringer Ingelheim Investigational Site	Vinnitsa

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Canada,  Croatia,  Estonia,  France,  Germany,  India,  Lithuania,  Mexico,  Netherlands,  Romania,  Russian Federation,  Sweden,  Tunisia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Patients With Adverse Events (AEs)	This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures.	54 weeks	No
Primary	Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	Baseline is defined as Visit 1 of 1218.52.	54 weeks	No
Primary	Change From Baseline at Week 54 in Pulse Rate	Baseline is defined as Visit 1 of 1218.52.	54 weeks	No
Primary	Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology		54 weeks	No
Primary	Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry	ULN means upper limit of normal	54 weeks	No
Primary	Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE	Frequency of patients with adverse events by treatment, primary system organ class and preferred term	Baseline and drug stop (up to 54 weeks) + 7 days	No
Secondary	Change in HbA1c From Baseline Over Time	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.	54 weeks	No
Secondary	Number of Patients With HbA1c <7.0% After 54 Weeks		54 weeks	No
Secondary	Number of Patients With HbA1c <6.5% Over Time		54 weeks	No
Secondary	Number of Patients With HbA1c of at Least <0.5% Over Time		54 weeks	No
Secondary	Change in FPG From Baseline Over Time	Baseline is defined as visit 1 of 1218.52.	54 weeks	No
Secondary	Number of Patients With Rescue Therapy		54 weeks	No
Secondary	Change in HbA1c From Baseline Over Time	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).	78 weeks	No

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