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

NCT00602472 | Completed Phase 3 Results

• 2 other identifiers: 1218.182007-002450-28
• Study Type: interventional
• Target: 1,058
• Locations: 11 countries
• Sites: 100

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (12)

• HbA1c Change From Baseline to Week 6

  Baseline and week 6

• HbA1c Change From Baseline to Week 12

  Baseline and week 12

• HbA1c Change From Baseline to Week 18

  Baseline and week 18

• FPG Change From Baseline to Week 24

  Baseline and week 24

• FPG Change From Baseline to Week 6

  Baseline and week 6

Study Arms (2)

linagliptin 5 mg

EXPERIMENTAL

linagliptin 5 mg once daily

Drug: linagliptin

placebo

PLACEBO COMPARATOR

placebo matching linagliptin 5 mg tablets

Drug: placebo

Interventions

linagliptin DRUG

active

linagliptin 5 mg

placebo DRUG

placebo to linagliptin 5 mg

placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Glycosylated haemoglobin A1 (HbA1c) \>/= 7.0 and \</= 10.0% at the screening Visit 1a and at Visit 2 (start of placebo run-in phase)
• Age \>/= 18 and \</= 80 years at Visit 1a (screening)
• BMI (Body Mass Index) \</= 40 kg/m2 at Visit 1a (screening)
• 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.

You may not qualify if:

• Myocardial infarction, stroke or TIA (transient ischaemic attack) within 6 months prior to the date of informed consent
• 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
• Renal failure or renal impairment (serum creatinine \>/= 1.5 mg/dl) as determined at Visit 1a
• Treatment with rosiglitazone or pioglitazone within 3 months prior to the date of informed consent
• Treatment with GLP-1 analogues (e.g. exenatide) within 3 months prior to the date of informed consent
• Treatment with insulin within 3 months prior to the date of informed consent
• Treatment with anti-obesity drugs (e.g. sibutramine, rimonabant, orlistat) within 3 months prior to the date of informed consent
• 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
• 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.
• 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
• Dehydration (as confirmed by the Investigators clinical opinion)
• Current acute or chronic metabolic acidosis

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (100)

1218.18.54001 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1218.18.54002 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1218.18.54004 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1218.18.54005 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1218.18.54010 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1218.18.54014 Boehringer Ingelheim Investigational Site

Corrientes, Argentina

Location

1218.18.54009 Boehringer Ingelheim Investigational Site

Córdoba, Argentina

Location

1218.18.54013 Boehringer Ingelheim Investigational Site

Córdoba, Argentina

Location

1218.18.54003 Boehringer Ingelheim Investigational Site

Mar del Plata, Argentina

Location

1218.18.54012 Boehringer Ingelheim Investigational Site

Mar del Plata, Argentina

Location

1218.18.54011 Boehringer Ingelheim Investigational Site

Mendoza, Argentina

Location

1218.18.54015 Boehringer Ingelheim Investigational Site

Parque Velez Sarfield, Argentina

Location

1218.18.54006 Boehringer Ingelheim Investigational Site

Rosario, Argentina

Location

1218.18.54007 Boehringer Ingelheim Investigational Site

Salta, Argentina

Location

1218.18.32005 Boehringer Ingelheim Investigational Site

Bruges, Belgium

Location

1218.18.32007 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1218.18.32006 Boehringer Ingelheim Investigational Site

Edegem, Belgium

Location

1218.18.32004 Boehringer Ingelheim Investigational Site

Genk, Belgium

Location

1218.18.32003 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Location

1218.18.32002 Boehringer Ingelheim Investigational Site

Huy, Belgium

Location

1218.18.32001 Boehringer Ingelheim Investigational Site

Liège, Belgium

Location

1218.18.01005 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

Location

1218.18.01010 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

Location

1218.18.01003 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1218.18.01011 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1218.18.01006 Boehringer Ingelheim Investigational Site

Etobicoke, Ontario, Canada

Location

1218.18.01009 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

1218.18.01002 Boehringer Ingelheim Investigational Site

London, Ontario, Canada

Location

1218.18.01012 Boehringer Ingelheim Investigational Site

Oakville, Ontario, Canada

Location

1218.18.01008 Boehringer Ingelheim Investigational Site

Sarnia, Ontario, Canada

Location

1218.18.01001 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1218.18.01004 Boehringer Ingelheim Investigational Site

Montague, Prince Edward Island, Canada

Location

1218.18.01007 Boehringer Ingelheim Investigational Site

Saskatoon, Saskatchewan, Canada

Location

1218.18.86001 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1218.18.86002 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1218.18.86004 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1218.18.86013 Boehringer Ingelheim Investigational Site

Chengdu, Sichuan Province, China

Location

1218.18.86009 Boehringer Ingelheim Investigational Site

Dalian, China

Location

1218.18.86011 Boehringer Ingelheim Investigational Site

Guangzhou, China

Location

1218.18.86014 Boehringer Ingelheim Investigational Site

Haerbin, China

Location

1218.18.86005 Boehringer Ingelheim Investigational Site

Nanjing, Jiangsu Province, China

Location

1218.18.86008 Boehringer Ingelheim Investigational Site

Qingdao, China

Location

1218.18.86015 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1218.18.86010 Boehringer Ingelheim Investigational Site

Shenyang, China

Location

1218.18.86003 Boehringer Ingelheim Investigational Site

Weizikeng, China

Location

1218.18.86007 Boehringer Ingelheim Investigational Site

Wuhan, China

Location

1218.18.86012 Boehringer Ingelheim Investigational Site

Wuhan, Hubei Province, China

Location

1218.18.86006 Boehringer Ingelheim Investigational Site

Xian, Shanxi Province, China

Location

1218.18.49004 Boehringer Ingelheim Investigational Site

Aschaffenburg, Germany

Location

1218.18.49028 Boehringer Ingelheim Investigational Site

Bad Mergentheim, Germany

Location

1218.18.49022 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1218.18.49024 Boehringer Ingelheim Investigational Site

Bosenheim, Germany

Location

1218.18.49020 Boehringer Ingelheim Investigational Site

Dresden, Germany

Location

1218.18.49101 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

1218.18.49003 Boehringer Ingelheim Investigational Site

Neuwied, Germany

Location

1218.18.49007 Boehringer Ingelheim Investigational Site

Nuremberg, Germany

Location

1218.18.49014 Boehringer Ingelheim Investigational Site

Saarbrücken, Germany

Location

1218.18.63005 Boehringer Ingelheim Investigational Site

Manila, Philippines

Location

1218.18.63002 Boehringer Ingelheim Investigational Site

Marikina City, Philippines

Location

1218.18.63001 Boehringer Ingelheim Investigational Site

Pasig, Philippines

Location

1218.18.63004 Boehringer Ingelheim Investigational Site

Quezon City, Philippines

Location

1218.18.63003 Boehringer Ingelheim Investigational Site

San Juan City, Philippines

Location

1218.18.70014 Boehringer Ingelheim Investigational Site

Arkhangelsk, Russia

Location

1218.18.70012 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

1218.18.70013 Boehringer Ingelheim Investigational Site

Rostov-on-Don, Russia

Location

1218.18.70015 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

1218.18.70016 Boehringer Ingelheim Investigational Site

Samara, Russia

Location

1218.18.82004 Boehringer Ingelheim Investigational Site

Busan, South Korea

Location

1218.18.82011 Boehringer Ingelheim Investigational Site

Daegu, South Korea

Location

1218.18.82008 Boehringer Ingelheim Investigational Site

Incheon, South Korea

Location

1218.18.82010 Boehringer Ingelheim Investigational Site

Jeonju, South Korea

Location

1218.18.82002 Boehringer Ingelheim Investigational Site

Pusan, South Korea

Location

1218.18.82001 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1218.18.82005 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1218.18.82006 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1218.18.82007 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1218.18.82009 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1218.18.82003 Boehringer Ingelheim Investigational Site

Suwon, South Korea

Location

1218.18.88605 Boehringer Ingelheim Investigational Site

Changhua, Taiwan

Location

1218.18.88604 Boehringer Ingelheim Investigational Site

Taichung, Taiwan

Location

1218.18.88606 Boehringer Ingelheim Investigational Site

Tainan, Taiwan

Location

1218.18.88601 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1218.18.88602 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1218.18.88603 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1218.18.88607 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1218.18.88608 Boehringer Ingelheim Investigational Site

Taoyuan District, Taiwan

Location

1218.18.90003 Boehringer Ingelheim Investigational Site

Erzurum, Turkey (Türkiye)

Location

1218.18.90005 Boehringer Ingelheim Investigational Site

Istanbul, Turkey (Türkiye)

Location

1218.18.90001 Boehringer Ingelheim Investigational Site

Izmir, Turkey (Türkiye)

Location

1218.18.90004 Boehringer Ingelheim Investigational Site

Konya, Turkey (Türkiye)

Location

1218.18.44005 Boehringer Ingelheim Investigational Site

Ashford, United Kingdom

Location

1218.18.44004 Boehringer Ingelheim Investigational Site

Baillieston, Glasgow, United Kingdom

Location

1218.18.44001 Boehringer Ingelheim Investigational Site

Bath, United Kingdom

Location

1218.18.44003 Boehringer Ingelheim Investigational Site

Burbage, United Kingdom

Location

1218.18.44010 Boehringer Ingelheim Investigational Site

Bury Saint Edmonds, United Kingdom

Location

1218.18.44009 Boehringer Ingelheim Investigational Site

Cardiff, United Kingdom

Location

1218.18.44008 Boehringer Ingelheim Investigational Site

Glasgow, United Kingdom

Location

1218.18.44002 Boehringer Ingelheim Investigational Site

Penarth, United Kingdom

Location

1218.18.44006 Boehringer Ingelheim Investigational Site

Reading, United Kingdom

Location

1218.18.44007 Boehringer Ingelheim Investigational Site

Waterloo, Liverpool, United Kingdom

Location

Related Publications (4)

• Del Prato S, Patel S, Crowe S, von Eynatten M. Efficacy and safety of linagliptin according to patient baseline characteristics: A pooled analysis of three phase 3 trials. Nutr Metab Cardiovasc Dis. 2016 Oct;26(10):886-92. doi: 10.1016/j.numecd.2016.06.015. Epub 2016 Jul 1.

  PMID: 27484756 DERIVED

• Zeng Z, Yang JK, Tong N, Yan S, Zhang X, Gong Y, Woerle HJ. Efficacy and safety of linagliptin added to metformin and sulphonylurea in Chinese patients with type 2 diabetes: a sub-analysis of data from a randomised clinical trial. Curr Med Res Opin. 2013 Aug;29(8):921-9. doi: 10.1185/03007995.2013.805123. Epub 2013 Jun 4.

  PMID: 23672632 DERIVED

• Johansen OE, Neubacher D, von Eynatten M, Patel S, Woerle HJ. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol. 2012 Jan 10;11:3. doi: 10.1186/1475-2840-11-3.

  PMID: 22234149 DERIVED

• Owens DR, Swallow R, Dugi KA, Woerle HJ. Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study. Diabet Med. 2011 Nov;28(11):1352-61. doi: 10.1111/j.1464-5491.2011.03387.x.

  PMID: 21781152 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Linagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 15, 2008
• First Posted: January 28, 2008
• Study Start: February 1, 2008
• Primary Completion: May 1, 2009
• Last Updated: March 28, 2014
• Results First Posted: June 15, 2011

Record last verified: 2014-02

Locations

DE (9); AR (14); TW (8); RU (5); BE (7); GB (10); CN (15); KR (11); CA (12); PH (5); TU (4)