Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With 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 (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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00601250
• Other study ID #: 1218.17
• Secondary ID: 2007-002457-24
• Status: Completed
• Phase: Phase 3
• First received: January 15, 2008
• Last updated: December 11, 2013
• Start date: January 2008

Study information

• Verified date: December 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10Finland: Finnish Medicines AgencyGreece: National Organization of Medicines (EOF) National Ethics CommitteeIndia: Ministry of Health and Family WelfareIsrael: Ministry of HealthMexico: Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS)New Zealand: Multicentre Ethics Committee/MedsafeRussia: Ministry of Healthcare and Social Development of Russian Federation, MoscowSweden: Sweden; Läkemedelsverket (Medical Product Agency)United 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 patients with type 2 diabetes mellitus with insufficient glycaemic control

Recruitment information / eligibility

• Status: Completed
• Enrollment: 701
• 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 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

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
Patients receive linagliptin 5 mg tablets once daily
• linagliptin
Patients receive linagliptin 5 mg tablets once daily

Locations

Country	Name	City	State
Czech Republic	1218.17.42006 Boehringer Ingelheim Investigational Site	Breclav
Czech Republic	1218.17.42001 Boehringer Ingelheim Investigational Site	Brno
Czech Republic	1218.17.42004 Boehringer Ingelheim Investigational Site	Brno
Czech Republic	1218.17.42007 Boehringer Ingelheim Investigational Site	Brno
Czech Republic	1218.17.42009 Boehringer Ingelheim Investigational Site	Brno
Czech Republic	1218.17.42008 Boehringer Ingelheim Investigational Site	Hodonin
Czech Republic	1218.17.42003 Boehringer Ingelheim Investigational Site	Olomouc
Finland	1218.17.35806 Boehringer Ingelheim Investigational Site	Helsinki
Finland	1218.17.35804 Boehringer Ingelheim Investigational Site	Jyväskylä
Finland	1218.17.35801 Boehringer Ingelheim Investigational Site	Kuopio
Finland	1218.17.35803 Boehringer Ingelheim Investigational Site	Oulu
Finland	1218.17.35805 Boehringer Ingelheim Investigational Site	Seinäjoki
Finland	1218.17.35802 Boehringer Ingelheim Investigational Site	Turku
Greece	1218.17.30004 Boehringer Ingelheim Investigational Site	Athens
Greece	1218.17.30013 Boehringer Ingelheim Investigational Site	Athens
Greece	1218.17.30011 Boehringer Ingelheim Investigational Site	Piraeus
India	1218.17.91009 Boehringer Ingelheim Investigational Site	Andhra Pradesh
India	1218.17.91002 Boehringer Ingelheim Investigational Site	Bangalore
India	1218.17.91005 Boehringer Ingelheim Investigational Site	Bangalore
India	1218.17.91012 Boehringer Ingelheim Investigational Site	Chennai
India	1218.17.91014 Boehringer Ingelheim Investigational Site	Chennai
India	1218.17.91010 Boehringer Ingelheim Investigational Site	Hyderabad
India	1218.17.91006 Boehringer Ingelheim Investigational Site	Jaipur
India	1218.17.91007 Boehringer Ingelheim Investigational Site	Karnataka
India	1218.17.91008 Boehringer Ingelheim Investigational Site	Mangalore
India	1218.17.91004 Boehringer Ingelheim Investigational Site	Mumbai
India	1218.17.91011 Boehringer Ingelheim Investigational Site	Nagpur
India	1218.17.91003 Boehringer Ingelheim Investigational Site	Nasik
India	1218.17.91001 Boehringer Ingelheim Investigational Site	Trivandrum
India	1218.17.91013 Boehringer Ingelheim Investigational Site	Uttar Pradesh
Israel	1218.17.97274 Boehringer Ingelheim Investigational Site	Afula
Israel	1218.17.97273 Boehringer Ingelheim Investigational Site	Haifa
Israel	1218.17.97275 Boehringer Ingelheim Investigational Site	Holon
Israel	1218.17.97271 Boehringer Ingelheim Investigational Site	Jerusalem
Israel	1218.17.97272 Boehringer Ingelheim Investigational Site	Nahariya
Israel	1218.17.97276 Boehringer Ingelheim Investigational Site	Safed
Israel	1218.17.97278 Boehringer Ingelheim Investigational Site	Tel Aviv
Mexico	1218.17.52007 Boehringer Ingelheim Investigational Site	Aguascalientes, Ags.
Mexico	1218.17.52009 Boehringer Ingelheim Investigational Site	cOL OBREGON,León, Guanajuato
Mexico	1218.17.52003 Boehringer Ingelheim Investigational Site	Col. Lomas de San Francisco, Monterrey
Mexico	1218.17.52001 Boehringer Ingelheim Investigational Site	Col. Mitras Centro, Monterrey, N.L.
Mexico	1218.17.52010 Boehringer Ingelheim Investigational Site	Col.Americana, Guadalajara, Jalisco
Mexico	1218.17.52005 Boehringer Ingelheim Investigational Site	Colonia Reforma Social
Mexico	1218.17.52008 Boehringer Ingelheim Investigational Site	Colonia Tlalpan, mexico
Mexico	1218.17.52006 Boehringer Ingelheim Investigational Site	Faccionamiento Lomas de Campestre,AGUASCAL
Mexico	1218.17.52002 Boehringer Ingelheim Investigational Site	Mexico
Mexico	1218.17.52004 Boehringer Ingelheim Investigational Site	Tlalpan-México D,F
New Zealand	1218.17.64004 Boehringer Ingelheim Investigational Site	Christchurch
New Zealand	1218.17.64003 Boehringer Ingelheim Investigational Site	Dunedin
New Zealand	1218.17.64002 Boehringer Ingelheim Investigational Site	Otahuhu
New Zealand	1218.17.64001 Boehringer Ingelheim Investigational Site	Tauranga
New Zealand	1218.17.64005 Boehringer Ingelheim Investigational Site	Wellington
Russian Federation	1218.17.70001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1218.17.70002 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1218.17.70003 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1218.17.70005 Boehringer Ingelheim Investigational Site	Novosibirsk
Russian Federation	1218.17.70006 Boehringer Ingelheim Investigational Site	Perm
Russian Federation	1218.17.70004 Boehringer Ingelheim Investigational Site	Tomsk
Sweden	1218.17.46013 Boehringer Ingelheim Investigational Site	Härnösand
Sweden	1218.17.46001 Boehringer Ingelheim Investigational Site	Malmö
Sweden	1218.17.46012 Boehringer Ingelheim Investigational Site	Uddevalla
Sweden	1218.17.46004 Boehringer Ingelheim Investigational Site	Uppsala
Sweden	1218.17.46015 Boehringer Ingelheim Investigational Site	Uppsala
United States	1218.17.10012 Boehringer Ingelheim Investigational Site	Charlotte	North Carolina
United States	1218.17.10003 Boehringer Ingelheim Investigational Site	Chula Vista	California
United States	1218.17.10005 Boehringer Ingelheim Investigational Site	Dallas	Texas
United States	1218.17.10016 Boehringer Ingelheim Investigational Site	Eugene	Oregon
United States	1218.17.10009 Boehringer Ingelheim Investigational Site	Federal Way	Washington
United States	1218.17.10002 Boehringer Ingelheim Investigational Site	Greer	South Carolina
United States	1218.17.10017 Boehringer Ingelheim Investigational Site	Gurnee	Illinois
United States	1218.17.10010 Boehringer Ingelheim Investigational Site	Hollywood	Florida
United States	1218.17.10018 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1218.17.10013 Boehringer Ingelheim Investigational Site	Mentor	Ohio
United States	1218.17.10011 Boehringer Ingelheim Investigational Site	Miami	Florida
United States	1218.17.10021 Boehringer Ingelheim Investigational Site	Northglenn	Colorado
United States	1218.17.10015 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma
United States	1218.17.10006 Boehringer Ingelheim Investigational Site	Omaha	Nebraska
United States	1218.17.10008 Boehringer Ingelheim Investigational Site	Pembroke Pines	Florida
United States	1218.17.10007 Boehringer Ingelheim Investigational Site	San Antonio	Texas
United States	1218.17.10004 Boehringer Ingelheim Investigational Site	Simpsonville	South Carolina
United States	1218.17.10014 Boehringer Ingelheim Investigational Site	Spring Valley	California
United States	1218.17.10001 Boehringer Ingelheim Investigational Site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Czech Republic,  Finland,  Greece,  India,  Israel,  Mexico,  New Zealand,  Russian Federation,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c Change From Baseline at 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 at 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 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. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and week 12	No
Secondary	HbA1c Change From Baseline at 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 at 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 at 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 at 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 at Week 18	This change from baseline reflects the Week 18 FPG minus the baseline 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 7.0% 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 >= 7.0%. 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 7.0% 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 >= 7.0%.	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 >= 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 >= 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 from baseline >= 0.5% 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 reduction less than 0.5%.	Baseline and week 24	No
Secondary	Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24	This change from baseline reflects the Week 24 2h PPG minus the baseline 2h PPG. Means are treatment adjusted for baseline HbA1c, baseline PPG and previous anti-diabetic medication.	Baseline and week 24	No
Secondary	2 Hour Post-Prandial Glucose (PPG) Increment Over Fasting Plasma Glucose (FPG) at Week 24	This change from baseline reflects the Week 24 (2h PPG - FPG) minus the baseline (2h PPG - FPG). Means are treatment adjusted for baseline HbA1c, baseline 2h PPG increment over FPG and previous anti-diabetic medication.	Baseline and week 24	No

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