Clinical trial NCT00601250: Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes
Official title: A Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 (One Dose, e.g. 5 mg), Administered Orally Once Daily Over 24 Weeks, With an Open Label Extension to 80 Weeks (Placebo Patients Switched to BI 1356), in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-01-28
Enrollment: 701
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 patients with type 2 diabetes mellitus with insufficient glycaemic control


Eligibility criteria: Inclusion criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone, or with metformin and not more than one other oral antidiabetic drug
2. Diagnosis of type 2 diabetes prior to informed consent
3. Glycosylated haemoglobin A1 (HbA1c)at screening:

   For patients undergoing wash out of previous medication: HbA1c 6.5 - 9.0% For patients not undergoing wash-out of previous medication: HbA1c 7.0 - 10.0%
4. Glycosylated haemoglobin A1 (HbA1c) 7.0 - 10.0% at the beginning of Placebo Run-in
5. Age 18 -80 years
6. BMI (Body Mass Index) less than 40 kg/m2
7. Signed and dated written informed consent by date of Visit 1a in accordance with GCP and local legislation

Exclusion criteria:

1. Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent
2. Impaired hepatic function
3. Known hypersensitivity or allergy to the investigational product or its excipients or metformin or placebo
4. Treatment with rosiglitazone or pioglitazone within 3 months prior to informed consent
5. Treatment with an injectable GLP-1 analogue (e.g. exenatide) within 3 months prior to informed consent
6. Treatment with insulin within 3 months prior to informed consent
7. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, rimonabant) within 3 months prior to informed consent
8. Alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or drug abuse
9. Participation in another trial with an investigational drug within 2 months prior to informed consent
10. Pre-menopausal women 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.
11. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
12. Renal failure or renal impairment
13. Unstable or acute congestive heart failure
14. Acute or chronic metabolic acidosis (present in patient history)
15. Hereditary galactose intolerance

Primary outcomes:
measure: HbA1c Change From Baseline at Week 24
timeFrame: Baseline and week 24
Secondary outcomes:
measure: HbA1c Change From Baseline at Week 6
timeFrame: Baseline and week 6
measure: HbA1c Change From Baseline at Week 12
timeFrame: Baseline and week 12
measure: HbA1c Change From Baseline at Week 18
timeFrame: Baseline and week 18
measure: FPG Change From Baseline at Week 24
timeFrame: Baseline and week 24
measure: FPG Change From Baseline at Week 6
timeFrame: Baseline and week 6
measure: FPG Change From Baseline at Week 12
timeFrame: Baseline and week 12
measure: FPG Change From Baseline at Week 18
timeFrame: Baseline and week 18
measure: Percentage of Patients With HbA1c <7.0% at Week 24.
timeFrame: Baseline and week 24
measure: Percentage of Patients With HbA1c < 7.0% at Week 24
timeFrame: Baseline and week 24
measure: Percentage of Patients With HbA1c <6.5% at Week 24
timeFrame: Baseline and week 24
measure: Percentage of Patients With HbA1c<6.5% at Week 24
timeFrame: Baseline and week 24
measure: Percentage of Patients Who Have a HbA1c Lowering by 0.5% at Week 24
timeFrame: Baseline and week 24
measure: Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24
timeFrame: Baseline and week 24
measure: 2 Hour Post-Prandial Glucose (PPG) Increment Over Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline and week 24
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: 1218.17.10003 Boehringer Ingelheim Investigational Site
state: California
city: Spring Valley
country: United States
facility: 1218.17.10014 Boehringer Ingelheim Investigational Site
state: California
city: Walnut Creek
country: United States
facility: 1218.17.10001 Boehringer Ingelheim Investigational Site
state: California
city: Northglenn
country: United States
facility: 1218.17.10021 Boehringer Ingelheim Investigational Site
state: Colorado
city: Hollywood
country: United States
facility: 1218.17.10010 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1218.17.10011 Boehringer Ingelheim Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: 1218.17.10008 Boehringer Ingelheim Investigational Site
state: Florida
city: Gurnee
country: United States
facility: 1218.17.10017 Boehringer Ingelheim Investigational Site
state: Illinois
city: Omaha
country: United States
facility: 1218.17.10006 Boehringer Ingelheim Investigational Site
state: Nebraska
city: Charlotte
country: United States
facility: 1218.17.10012 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Mentor
country: United States
facility: 1218.17.10013 Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: 1218.17.10015 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Eugene
country: United States
facility: 1218.17.10016 Boehringer Ingelheim Investigational Site
state: Oregon
city: Greer
country: United States
facility: 1218.17.10002 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Simpsonville
country: United States
facility: 1218.17.10004 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: 1218.17.10005 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1218.17.10018 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1218.17.10007 Boehringer Ingelheim Investigational Site
state: Texas
city: Federal Way
country: United States
facility: 1218.17.10009 Boehringer Ingelheim Investigational Site
state: Washington
city: Breclav
country: Czech Republic
facility: 1218.17.42006 Boehringer Ingelheim Investigational Site
city: Brno
country: Czech Republic
facility: 1218.17.42001 Boehringer Ingelheim Investigational Site
city: Brno
country: Czech Republic
facility: 1218.17.42004 Boehringer Ingelheim Investigational Site
city: Brno
country: Czech Republic
facility: 1218.17.42007 Boehringer Ingelheim Investigational Site
city: Brno
country: Czech Republic
facility: 1218.17.42009 Boehringer Ingelheim Investigational Site
city: Hodonin
country: Czech Republic
facility: 1218.17.42008 Boehringer Ingelheim Investigational Site
city: Olomouc
country: Czech Republic
facility: 1218.17.42003 Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: 1218.17.35806 Boehringer Ingelheim Investigational Site
city: Jyväskylä
country: Finland
facility: 1218.17.35804 Boehringer Ingelheim Investigational Site
city: Kuopio
country: Finland
facility: 1218.17.35801 Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: 1218.17.35803 Boehringer Ingelheim Investigational Site
city: Seinäjoki
country: Finland
facility: 1218.17.35805 Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: 1218.17.35802 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1218.17.30004 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1218.17.30013 Boehringer Ingelheim Investigational Site
city: Piraeus
country: Greece
facility: 1218.17.30011 Boehringer Ingelheim Investigational Site
city: Andhra Pradesh
country: India
facility: 1218.17.91009 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1218.17.91002 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1218.17.91005 Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: 1218.17.91012 Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: 1218.17.91014 Boehringer Ingelheim Investigational Site
city: Hyderabad
country: India
facility: 1218.17.91010 Boehringer Ingelheim Investigational Site
city: Jaipur
country: India
facility: 1218.17.91006 Boehringer Ingelheim Investigational Site
city: Karnataka
country: India
facility: 1218.17.91007 Boehringer Ingelheim Investigational Site
city: Mangalore
country: India
facility: 1218.17.91008 Boehringer Ingelheim Investigational Site
city: Mumbai
country: India
facility: 1218.17.91004 Boehringer Ingelheim Investigational Site
city: Nagpur
country: India
facility: 1218.17.91011 Boehringer Ingelheim Investigational Site
city: Nasik
country: India
facility: 1218.17.91003 Boehringer Ingelheim Investigational Site
city: Trivandrum
country: India
facility: 1218.17.91001 Boehringer Ingelheim Investigational Site
city: Uttar Pradesh
country: India
facility: 1218.17.91013 Boehringer Ingelheim Investigational Site
city: Afula
country: Israel
facility: 1218.17.97274 Boehringer Ingelheim Investigational Site
city: Haifa
country: Israel
facility: 1218.17.97273 Boehringer Ingelheim Investigational Site
city: Holon
country: Israel
facility: 1218.17.97275 Boehringer Ingelheim Investigational Site
city: Jerusalem
country: Israel
facility: 1218.17.97271 Boehringer Ingelheim Investigational Site
city: Nahariya
country: Israel
facility: 1218.17.97272 Boehringer Ingelheim Investigational Site
city: Safed
country: Israel
facility: 1218.17.97276 Boehringer Ingelheim Investigational Site
city: Tel Aviv
country: Israel
facility: 1218.17.97278 Boehringer Ingelheim Investigational Site
city: Aguascalientes, Ags.
country: Mexico
facility: 1218.17.52007 Boehringer Ingelheim Investigational Site
city: cOL OBREGON,León, Guanajuato
country: Mexico
facility: 1218.17.52009 Boehringer Ingelheim Investigational Site
city: Col. Lomas de San Francisco, Monterrey
country: Mexico
facility: 1218.17.52003 Boehringer Ingelheim Investigational Site
city: Col. Mitras Centro, Monterrey, N.L.
country: Mexico
facility: 1218.17.52001 Boehringer Ingelheim Investigational Site
city: Col.Americana, Guadalajara, Jalisco
country: Mexico
facility: 1218.17.52010 Boehringer Ingelheim Investigational Site
city: Colonia Reforma Social
country: Mexico
facility: 1218.17.52005 Boehringer Ingelheim Investigational Site
city: Colonia Tlalpan, mexico
country: Mexico
facility: 1218.17.52008 Boehringer Ingelheim Investigational Site
city: Faccionamiento Lomas de Campestre,AGUASCAL
country: Mexico
facility: 1218.17.52006 Boehringer Ingelheim Investigational Site
city: Mexico
country: Mexico
facility: 1218.17.52002 Boehringer Ingelheim Investigational Site
city: Tlalpan-México D,F
country: Mexico
facility: 1218.17.52004 Boehringer Ingelheim Investigational Site
city: Christchurch
country: New Zealand
facility: 1218.17.64004 Boehringer Ingelheim Investigational Site
city: Dunedin
country: New Zealand
facility: 1218.17.64003 Boehringer Ingelheim Investigational Site
city: Otahuhu
country: New Zealand
facility: 1218.17.64002 Boehringer Ingelheim Investigational Site
city: Tauranga
country: New Zealand
facility: 1218.17.64001 Boehringer Ingelheim Investigational Site
city: Wellington
country: New Zealand
facility: 1218.17.64005 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.17.70001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.17.70002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.17.70003 Boehringer Ingelheim Investigational Site
city: Novosibirsk
country: Russian Federation
facility: 1218.17.70005 Boehringer Ingelheim Investigational Site
city: Perm
country: Russian Federation
facility: 1218.17.70006 Boehringer Ingelheim Investigational Site
city: Tomsk
country: Russian Federation
facility: 1218.17.70004 Boehringer Ingelheim Investigational Site
city: Härnösand
country: Sweden
facility: 1218.17.46013 Boehringer Ingelheim Investigational Site
city: Malmö
country: Sweden
facility: 1218.17.46001 Boehringer Ingelheim Investigational Site
city: Uddevalla
country: Sweden
facility: 1218.17.46012 Boehringer Ingelheim Investigational Site
city: Uppsala
country: Sweden
facility: 1218.17.46004 Boehringer Ingelheim Investigational Site
city: Uppsala
country: Sweden
facility: 1218.17.46015 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.