Linagliptin 2.5 mg Twice Daily Versus 5 mg Once Daily as add-on Therapy to Twice Daily Metformin in Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

12 Week Randomised Double-blind BI 1356 2.5 mg Bid vs 5 mg qd add-on to Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01012037
• Other study ID #: 1218.62
• Secondary ID: 2009-013549-27
• Status: Completed
• Phase: Phase 2
• First received: November 10, 2009
• Last updated: June 17, 2014
• Start date: November 2009

Study information

• Verified date: December 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal and Health ProductsCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)India: Drugs Controller General of IndiaItaly: Ethics CommitteeMalaysia: Ministry of HealthNetherlands: Central Committee Research Involving Human SubjectsSouth Korea: Korea Food and Drug Administration (KFDA)Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 491
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• linagliptin low dose
patient to receive tablets containing low dose linagliptin twice daily
• placebo
patient to receive placebo tablet(s) matching linagliptin
• linagliptin medium dose
patient to receive a tablet containing medium dose linagliptin once daily

Locations

Country	Name	City	State
Belgium	1218.62.32003 Boehringer Ingelheim Investigational Site	De Pinte
Belgium	1218.62.32008 Boehringer Ingelheim Investigational Site	Kortenaken
Belgium	1218.62.32009 Boehringer Ingelheim Investigational Site	Kumtich
Belgium	1218.62.32005 Boehringer Ingelheim Investigational Site	Massemen-Wetteren
Belgium	1218.62.32004 Boehringer Ingelheim Investigational Site	Natoye
Belgium	1218.62.32007 Boehringer Ingelheim Investigational Site	Sint-Job-in't-Goor
Belgium	1218.62.32002 Boehringer Ingelheim Investigational Site	Tessenderlo
Belgium	1218.62.32006 Boehringer Ingelheim Investigational Site	Wilsele
Canada	1218.62.11001 Boehringer Ingelheim Investigational Site	Barrie	Ontario
Canada	1218.62.11003 Boehringer Ingelheim Investigational Site	Brampton	Ontario
Canada	1218.62.11007 Boehringer Ingelheim Investigational Site	Burnaby	British Columbia
Canada	1218.62.11012 Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	1218.62.11010 Boehringer Ingelheim Investigational Site	Charlottetown	Prince Edward Island
Canada	1218.62.11006 Boehringer Ingelheim Investigational Site	Halifax	Nova Scotia
Canada	1218.62.11004 Boehringer Ingelheim Investigational Site	Markham	Ontario
Canada	1218.62.11002 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1218.62.11009 Boehringer Ingelheim Investigational Site	Point Claire	Quebec
Canada	1218.62.11005 Boehringer Ingelheim Investigational Site	Sarnia	Ontario
Canada	1218.62.11008 Boehringer Ingelheim Investigational Site	Smiths Falls	Ontario
Canada	1218.62.11011 Boehringer Ingelheim Investigational Site	St. John's	Newfoundland and Labrador
Canada	1218.62.11013 Boehringer Ingelheim Investigational Site	Strathroy	Ontario
Canada	1218.62.11014 Boehringer Ingelheim Investigational Site	Toronto	Ontario
France	1218.62.3303C Boehringer Ingelheim Investigational Site	Bort les Orgues
France	1218.62.3306A Boehringer Ingelheim Investigational Site	Bourg des cptes
France	1218.62.3303D Boehringer Ingelheim Investigational Site	Bugeat
France	1218.62.3302H Boehringer Ingelheim Investigational Site	Corsept
France	1218.62.3308A Boehringer Ingelheim Investigational Site	Derval
France	1218.62.3302B Boehringer Ingelheim Investigational Site	La Chapelle sur Erdre
France	1218.62.3304A Boehringer Ingelheim Investigational Site	Levallois Perret
France	1218.62.3305A Boehringer Ingelheim Investigational Site	Marseille
France	1218.62.3305B Boehringer Ingelheim Investigational Site	Marseille
France	1218.62.3305G Boehringer Ingelheim Investigational Site	Marseille
France	1218.62.3305H Boehringer Ingelheim Investigational Site	Marseille
France	1218.62.3302A Boehringer Ingelheim Investigational Site	Nantes
France	1218.62.3301A Boehringer Ingelheim Investigational Site	Nantes Cedex 1
France	1218.62.3304B Boehringer Ingelheim Investigational Site	Paris
France	1218.62.3304D Boehringer Ingelheim Investigational Site	Paris
France	1218.62.3305F Boehringer Ingelheim Investigational Site	Roquevaire
France	1218.62.3305I Boehringer Ingelheim Investigational Site	Roquevaire
France	1218.62.3303A Boehringer Ingelheim Investigational Site	Rosiers d'Egletons
France	1218.62.3303H Boehringer Ingelheim Investigational Site	Sainte Fortunade
France	1218.62.3302I Boehringer Ingelheim Investigational Site	Sautron
France	1218.62.3302G Boehringer Ingelheim Investigational Site	VUE
India	1218.62.91001 Boehringer Ingelheim Investigational Site	Bangalore
India	1218.62.91004 Boehringer Ingelheim Investigational Site	Bangalore
India	1218.62.91003 Boehringer Ingelheim Investigational Site	Hyderabad, Andra Pradesh
India	1218.62.91005 Boehringer Ingelheim Investigational Site	Nagpru
India	1218.62.91002 Boehringer Ingelheim Investigational Site	Trivandrum
Italy	1218.62.39010 Boehringer Ingelheim Investigational Site	Ancona
Italy	1218.62.39006 Boehringer Ingelheim Investigational Site	Catania
Italy	1218.62.39004 Boehringer Ingelheim Investigational Site	Genova
Italy	1218.62.39009 Boehringer Ingelheim Investigational Site	Gissi (CH)
Italy	1218.62.39003 Boehringer Ingelheim Investigational Site	Palermo
Italy	1218.62.39001 Boehringer Ingelheim Investigational Site	Pisa
Italy	1218.62.39002 Boehringer Ingelheim Investigational Site	Pordenone
Italy	1218.62.39012 Boehringer Ingelheim Investigational Site	Ravenna
Italy	1218.62.39007 Boehringer Ingelheim Investigational Site	Roma
Italy	1218.62.39011 Boehringer Ingelheim Investigational Site	Roma
Korea, Republic of	1218.62.82005 Boehringer Ingelheim Investigational Site	Goyang
Korea, Republic of	1218.62.82006 Boehringer Ingelheim Investigational Site	Goyang
Korea, Republic of	1218.62.82003 Boehringer Ingelheim Investigational Site	Incheon
Korea, Republic of	1218.62.82004 Boehringer Ingelheim Investigational Site	Pucheon
Korea, Republic of	1218.62.82002 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1218.62.82001 Boehringer Ingelheim Investigational Site	Suwon
Malaysia	1218.62.60001 Boehringer Ingelheim Investigational Site	Kelantan Kota Bahru
Malaysia	1218.62.60005 Boehringer Ingelheim Investigational Site	Kuala Lumpur
Malaysia	1218.62.60002 Boehringer Ingelheim Investigational Site	Penang
Malaysia	1218.62.60003 Boehringer Ingelheim Investigational Site	Putrajaya
Malaysia	1218.62.60004 Boehringer Ingelheim Investigational Site	Seremban
Netherlands	1218.62.31007 Boehringer Ingelheim Investigational Site	Almere
Netherlands	1218.62.31004 Boehringer Ingelheim Investigational Site	Breezerveld
Netherlands	1218.62.31005 Boehringer Ingelheim Investigational Site	Etten-Leur
Netherlands	1218.62.31002 Boehringer Ingelheim Investigational Site	Lieshout
Netherlands	1218.62.31001 Boehringer Ingelheim Investigational Site	Oude Pekela
Netherlands	1218.62.31008 Boehringer Ingelheim Investigational Site	Voerendaal
Netherlands	1218.62.31009 Boehringer Ingelheim Investigational Site	Wildervank
Netherlands	1218.62.31003 Boehringer Ingelheim Investigational Site	Woerden
Spain	1218.62.34003 Boehringer Ingelheim Investigational Site	Badia del Vallés (Barcelona)
Spain	1218.62.34002 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat (Barcelona)
Spain	1218.62.34005 Boehringer Ingelheim Investigational Site	Madrid
Spain	1218.62.34006 Boehringer Ingelheim Investigational Site	Madrid
Spain	1218.62.34007 Boehringer Ingelheim Investigational Site	Madrid
Spain	1218.62.34001 Boehringer Ingelheim Investigational Site	Palma (Mallorca)
Spain	1218.62.34008 Boehringer Ingelheim Investigational Site	Palma de Mallorca

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Belgium,  Canada,  France,  India,  Italy,  Korea, Republic of,  Malaysia,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c Change From Baseline at Week 12	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Treatment means are adjusted for baseline HbA1c and use of prior oral antidiabetics (OADs) in addition to background metformin.	Baseline and week 12	No
Secondary	HbA1c Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis	Mixed model includes treatment, baseline HbA1c, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.	Baseline and week 6	No
Secondary	HbA1c Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis	Mixed model includes treatment, baseline HbA1c, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.	Baseline and week 12	No
Secondary	FPG Change From Baseline at Week 12	Change from baseline reflects the Week 12 FPG minus the baseline FPG. Treatment means are adjusted for baseline HbA1c, baseline fasting plasma glucose and use of prior oral antidiabetics (OADs) in addition to background metformin.	Baseline and week 12	No
Secondary	FPG Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis	Mixed model includes treatment, baseline HbA1c, baseline FPG, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.	Baseline and week 6	No
Secondary	FPG Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis	Mixed model includes treatment, baseline HbA1c, baseline FPG, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.	Baseline and week 12	No
Secondary	Percentage of Patients With HbA1c Lowering by 0.5% or More at Week 12	Percentage of patients with HbA1c lowering by at least 0.5% after 12 weeks. The analysis was performed on the full analysis set (FAS) using NCF.	Week 12	No
Secondary	Percentage of Patients With Rescue Therapy	Percentage of patients with rescue therapy at Week 12. The analysis was performed on the full analysis set (FAS) using OC.	12 weeks	No
Secondary	The Occurrence of a Treat to Target Efficacy Response (HbA1c <7.0%) After 12 Weeks of Treatment	Percentage of those patients with baseline HbA1c >= 7.0% who had HbA1c < 7% at Week 12. The analysis was performed on the full analysis set (FAS) using NCF.	12 weeks	No
Secondary	The Occurrence of a Treat to Target Efficacy Response (HbA1c <6.5 %) After 12 Weeks of Treatment	Percentage of those patients with baseline HbA1c >= 6.5% who had HbA1c < 6.5% at Week 12. The analysis was performed on the full analysis set (FAS) using NCF.	12 weeks	No

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