BI 1356 (Linagliptin) in Combination With Metformin and a Sulphonylurea in Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 (5 mg) Administered Orally Once Daily Over 24 Weeks, With an Open-label Extension to One Year (Placebo Patients Switched to BI 1356), in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite a Therapy of Metformin in Combination With a Sulphonylurea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00602472
• Other study ID #: 1218.18
• Secondary ID: 2007-002450-28
• Status: Completed
• Phase: Phase 3
• First received: January 15, 2008
• Last updated: February 27, 2014
• Start date: February 2008

Study information

• Verified date: February 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Ministry of HealthBelgium: Federal Agency for Medicines and Health Products, FAMHPCanada: Therapeutic Products DirectorateChina: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesGreat Britain: MHRAKorea, Republic of: Korea Food and Drug AdministrationPhilippines: Department of HealthRussia: Ministry of Healthcare and Social Development of Russian Federation, MoscowTaiwan: Dept of Health TaiwanTurkey: Ministery of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (5 mg once daily) compared to placebo given for 24 weeks as add-on therapy to metformin in combination with a sulphonylurea in patients with type 2 diabetes mellitus with insufficient glycaemic control.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1058
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus, currently treated only with a stable total daily dose of preferably* >/= 1500 mg metformin and a dose of a sulphonylurea drug that has been documented, by the Investigator, to be the individual maximum tolerated dose of that sulphonylurea drug. Both the dose and dosing regimen of metformin and the sulphonylurea must be stable (i.e. unchanged) for 10 weeks prior to informed consent, and must not be changed for the duration of the trial

2. Glycosylated haemoglobin A1 (HbA1c) >/= 7.0 and </= 10.0% at the screening Visit 1a and at Visit 2 (start of placebo run-in phase)

3. Age >/= 18 and </= 80 years at Visit 1a (screening)

4. BMI (Body Mass Index) </= 40 kg/m2 at Visit 1a (screening)

5. Signed and dated written informed consent, at the latest by the date of Visit 1a, in accordance with GCP and local legislation *Patients currently treated with a total daily dose of less than 1500 mg metformin can be included in the trial if the Investigator has documented that the dose is the maximum tolerated dose of metformin for that patient.

Exclusion criteria:

1. Myocardial infarction, stroke or TIA (transient ischaemic attack) within 6 months prior to the date of informed consent

2. Impaired hepatic function, defined by serum levels of either alanine transaminase (ALT/SGPT), aspartase transaminase (AST/SGOT), or alkaline phosphatase (ALP) above 3 times the upper limit of normal (ULN), as determined at Visit 1a

3. Renal failure or renal impairment (serum creatinine >/= 1.5 mg/dl) as determined at Visit 1a

4. Treatment with rosiglitazone or pioglitazone within 3 months prior to the date of informed consent

5. Treatment with GLP-1 analogues (e.g. exenatide) within 3 months prior to the date of informed consent

6. Treatment with insulin within 3 months prior to the date of informed consent

7. Treatment with anti-obesity drugs (e.g. sibutramine, rimonabant, orlistat) within 3 months prior to the date of informed consent

8. Current treatment with systemic steroids (i.e. at the time of informed consent) or a change in the dosage of thyroid hormones within 6 weeks prior to the date of informed consent

9. Pre-menopausal women (last menstruation </= 1 year prior to the date of 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 periodic pregnancy testing during their 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. No exception will be made.

10. Known hypersensitivity or allergy to the investigational product or its excipients or to the trial background therapy (i.e. metformin in combination with a sulphonylurea) or sulphonamides

11. Dehydration (as confirmed by the Investigators clinical opinion)

12. Current acute or chronic metabolic acidosis

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
active
• placebo
placebo to linagliptin 5 mg

Locations

Country	Name	City	State
Argentina	1218.18.54001 Boehringer Ingelheim Investigational Site	Capital Federal
Argentina	1218.18.54002 Boehringer Ingelheim Investigational Site	Capital Federal
Argentina	1218.18.54004 Boehringer Ingelheim Investigational Site	Capital Federal
Argentina	1218.18.54005 Boehringer Ingelheim Investigational Site	Capital Federal
Argentina	1218.18.54010 Boehringer Ingelheim Investigational Site	Capital Federal
Argentina	1218.18.54009 Boehringer Ingelheim Investigational Site	Córdoba
Argentina	1218.18.54013 Boehringer Ingelheim Investigational Site	Córdoba
Argentina	1218.18.54014 Boehringer Ingelheim Investigational Site	Corrientes
Argentina	1218.18.54003 Boehringer Ingelheim Investigational Site	Mar del Plata
Argentina	1218.18.54012 Boehringer Ingelheim Investigational Site	Mar del Plata
Argentina	1218.18.54011 Boehringer Ingelheim Investigational Site	Mendoza
Argentina	1218.18.54015 Boehringer Ingelheim Investigational Site	Parque Velez Sarfield
Argentina	1218.18.54006 Boehringer Ingelheim Investigational Site	Rosario
Argentina	1218.18.54007 Boehringer Ingelheim Investigational Site	Salta
Belgium	1218.18.32005 Boehringer Ingelheim Investigational Site	Brugge
Belgium	1218.18.32007 Boehringer Ingelheim Investigational Site	Brussel
Belgium	1218.18.32006 Boehringer Ingelheim Investigational Site	Edegem
Belgium	1218.18.32004 Boehringer Ingelheim Investigational Site	Genk
Belgium	1218.18.32003 Boehringer Ingelheim Investigational Site	Gent
Belgium	1218.18.32002 Boehringer Ingelheim Investigational Site	Huy
Belgium	1218.18.32001 Boehringer Ingelheim Investigational Site	Liège
Canada	1218.18.01005 Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	1218.18.01010 Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	1218.18.01006 Boehringer Ingelheim Investigational Site	Etobicoke	Ontario
Canada	1218.18.01009 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1218.18.01002 Boehringer Ingelheim Investigational Site	London	Ontario
Canada	1218.18.01004 Boehringer Ingelheim Investigational Site	Montague	Prince Edward Island
Canada	1218.18.01012 Boehringer Ingelheim Investigational Site	Oakville	Ontario
Canada	1218.18.01008 Boehringer Ingelheim Investigational Site	Sarnia	Ontario
Canada	1218.18.01007 Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan
Canada	1218.18.01001 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1218.18.01003 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	1218.18.01011 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
China	1218.18.86001 Boehringer Ingelheim Investigational Site	Beijing
China	1218.18.86002 Boehringer Ingelheim Investigational Site	Beijing
China	1218.18.86004 Boehringer Ingelheim Investigational Site	Beijing
China	1218.18.86013 Boehringer Ingelheim Investigational Site	Chengdu, Sichuan Province
China	1218.18.86009 Boehringer Ingelheim Investigational Site	Dalian
China	1218.18.86011 Boehringer Ingelheim Investigational Site	Guangzhou
China	1218.18.86014 Boehringer Ingelheim Investigational Site	Haerbin
China	1218.18.86005 Boehringer Ingelheim Investigational Site	Nanjing, Jiangsu Province
China	1218.18.86008 Boehringer Ingelheim Investigational Site	Qingdao
China	1218.18.86015 Boehringer Ingelheim Investigational Site	Shanghai
China	1218.18.86010 Boehringer Ingelheim Investigational Site	Shen Yang
China	1218.18.86003 Boehringer Ingelheim Investigational Site	Weizikeng
China	1218.18.86007 Boehringer Ingelheim Investigational Site	Wuhan
China	1218.18.86012 Boehringer Ingelheim Investigational Site	Wuhan, Hubei Province
China	1218.18.86006 Boehringer Ingelheim Investigational Site	Xian, Shanxi Province
Germany	1218.18.49004 Boehringer Ingelheim Investigational Site	Aschaffenburg
Germany	1218.18.49028 Boehringer Ingelheim Investigational Site	Bad Mergentheim
Germany	1218.18.49022 Boehringer Ingelheim Investigational Site	Berlin
Germany	1218.18.49024 Boehringer Ingelheim Investigational Site	Bosenheim
Germany	1218.18.49020 Boehringer Ingelheim Investigational Site	Dresden
Germany	1218.18.49101 Boehringer Ingelheim Investigational Site	Mainz
Germany	1218.18.49003 Boehringer Ingelheim Investigational Site	Neuwied
Germany	1218.18.49007 Boehringer Ingelheim Investigational Site	Nürnberg
Germany	1218.18.49014 Boehringer Ingelheim Investigational Site	Saarbrücken
Korea, Republic of	1218.18.82004 Boehringer Ingelheim Investigational Site	Busan
Korea, Republic of	1218.18.82011 Boehringer Ingelheim Investigational Site	Daegu
Korea, Republic of	1218.18.82008 Boehringer Ingelheim Investigational Site	Incheon
Korea, Republic of	1218.18.82010 Boehringer Ingelheim Investigational Site	Jeonju
Korea, Republic of	1218.18.82002 Boehringer Ingelheim Investigational Site	Pusan
Korea, Republic of	1218.18.82001 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1218.18.82005 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1218.18.82006 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1218.18.82007 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1218.18.82009 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1218.18.82003 Boehringer Ingelheim Investigational Site	Suwon
Philippines	1218.18.63005 Boehringer Ingelheim Investigational Site	Manila
Philippines	1218.18.63002 Boehringer Ingelheim Investigational Site	Marikina
Philippines	1218.18.63001 Boehringer Ingelheim Investigational Site	Pasig
Philippines	1218.18.63004 Boehringer Ingelheim Investigational Site	Quezon City
Philippines	1218.18.63003 Boehringer Ingelheim Investigational Site	San Juan
Russian Federation	1218.18.70014 Boehringer Ingelheim Investigational Site	Arkhangelsk
Russian Federation	1218.18.70012 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1218.18.70013 Boehringer Ingelheim Investigational Site	Rostov-on-Don
Russian Federation	1218.18.70016 Boehringer Ingelheim Investigational Site	Samara
Russian Federation	1218.18.70015 Boehringer Ingelheim Investigational Site	St. Petersburg
Taiwan	1218.18.88605 Boehringer Ingelheim Investigational Site	Changhua
Taiwan	1218.18.88604 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1218.18.88606 Boehringer Ingelheim Investigational Site	Tainan
Taiwan	1218.18.88601 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1218.18.88602 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1218.18.88603 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1218.18.88607 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1218.18.88608 Boehringer Ingelheim Investigational Site	Taoyuan
Turkey	1218.18.90003 Boehringer Ingelheim Investigational Site	Erzurum
Turkey	1218.18.90005 Boehringer Ingelheim Investigational Site	Istanbul
Turkey	1218.18.90001 Boehringer Ingelheim Investigational Site	Izmir
Turkey	1218.18.90004 Boehringer Ingelheim Investigational Site	Konya
United Kingdom	1218.18.44005 Boehringer Ingelheim Investigational Site	Ashford
United Kingdom	1218.18.44004 Boehringer Ingelheim Investigational Site	Baillieston, Glasgow
United Kingdom	1218.18.44001 Boehringer Ingelheim Investigational Site	Bath
United Kingdom	1218.18.44003 Boehringer Ingelheim Investigational Site	Burbage
United Kingdom	1218.18.44010 Boehringer Ingelheim Investigational Site	Bury St Edmonds
United Kingdom	1218.18.44009 Boehringer Ingelheim Investigational Site	Cardiff
United Kingdom	1218.18.44008 Boehringer Ingelheim Investigational Site	Glasgow
United Kingdom	1218.18.44002 Boehringer Ingelheim Investigational Site	Penarth
United Kingdom	1218.18.44006 Boehringer Ingelheim Investigational Site	Reading
United Kingdom	1218.18.44007 Boehringer Ingelheim Investigational Site	Waterloo, Liverpool

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Argentina,  Belgium,  Canada,  China,  Germany,  Korea, Republic of,  Philippines,  Russian Federation,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c Change From Baseline to Week 24	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and week 24	No
Secondary	HbA1c Change From Baseline to Week 6	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and week 6	No
Secondary	HbA1c Change From Baseline to Week 12	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and week 12	No
Secondary	HbA1c Change From Baseline to Week 18	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and week 18	No
Secondary	FPG Change From Baseline to Week 24	This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.	Baseline and week 24	No
Secondary	FPG Change From Baseline to Week 6	This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.	Baseline and week 6	No
Secondary	FPG Change From Baseline to Week 12	This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.	Baseline and week 12	No
Secondary	FPG Change From Baseline to Week 18	This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication	Baseline and week 18	No
Secondary	Percentage of Patients With HbA1c <7.0% at Week 24	The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%. Only patients with baseline HbA1c >= 7%	Baseline and week 24	No
Secondary	Percentage of Patients With HbA1c < 7.0% at Week 24	The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.	Baseline and week 24	No
Secondary	Percentage of Patients With HbA1c <6.5% at Week 24	The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%. Only patients with baseline HbA1c >= 6.5%	Baseline and week 24	No
Secondary	Percentage of Patients With HbA1c<6.5% at Week 24	The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%	Baseline and week 24	No
Secondary	Percentage of Patients Who Have a HbA1c Lowering by 0.5% at Week 24	The percentage of patients with an HbA1c reduction greater than 0.5% at week 24 from baseline was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%	Baseline and week 24	No

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