Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT00601250
• Recruitment Status: Completed
• First Posted: January 28, 2008
• Results First Posted: June 7, 2011
• Last Update Posted: January 28, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by: Boehringer Ingelheim

Tracking Information

• First Submitted Date: January 15, 2008
• First Posted Date: January 28, 2008
• Results First Submitted Date: May 13, 2011
• Results First Posted Date: June 7, 2011
• Last Update Posted Date: January 28, 2014
• Study Start Date: January 2008
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 13, 2011)

HbA1c Change From Baseline at Week 24 [ Time Frame: Baseline and 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.

• Original Primary Outcome Measures (submitted: January 15, 2008): The primary endpoint in this study is the change from baseline in HbA1c (HbA1c after 24 weeks of treatment).

Current Secondary Outcome Measures (submitted: December 11, 2013)

• HbA1c Change From Baseline at Week 6 [ Time Frame: Baseline and 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.
• HbA1c Change From Baseline at Week 12 [ Time Frame: Baseline and 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.
• HbA1c Change From Baseline at Week 18 [ Time Frame: Baseline and 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.
• FPG Change From Baseline at Week 24 [ Time Frame: Baseline and 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.
• FPG Change From Baseline at Week 6 [ Time Frame: Baseline and 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.
• FPG Change From Baseline at Week 12 [ Time Frame: Baseline and 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.
• FPG Change From Baseline at Week 18 [ Time Frame: Baseline and 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.
• Percentage of Patients With HbA1c <7.0% at Week 24. [ Time Frame: Baseline and 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%
• Percentage of Patients With HbA1c < 7.0% at Week 24 [ Time Frame: Baseline and 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%.
• Percentage of Patients With HbA1c <6.5% at Week 24 [ Time Frame: Baseline and 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%
• Percentage of Patients With HbA1c<6.5% at Week 24 [ Time Frame: Baseline and 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%.
• Percentage of Patients Who Have a HbA1c Lowering by 0.5% at Week 24 [ Time Frame: Baseline and 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%.
• Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24 [ Time Frame: Baseline and 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.
• 2 Hour Post-Prandial Glucose (PPG) Increment Over Fasting Plasma Glucose (FPG) at Week 24 [ Time Frame: Baseline and 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.

• Original Secondary Outcome Measures (submitted: January 15, 2008): change from baseline in HbA1c, change from baseline in FPG, Change from baseline in Postprandial glucose
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

Drug: linagliptin

Patients receive linagliptin 5 mg tablets once daily

Study Arms

• Experimental: Linagliptin
  Patients receive linagliptin 5 mg tablets once daily
  Intervention: Drug: linagliptin
• Placebo Comparator: Placebo
  Patients receive placebo tablets matching linagliptin 5 mg tablets once daily
  Intervention: Drug: linagliptin

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 5, 2011): 701
• Original Enrollment (submitted: January 15, 2008): 600
• Study Completion Date: Not Provided
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czech Republic, Finland, Greece, India, Israel, Mexico, New Zealand, Russian Federation, Sweden, United States

Administrative Information

• NCT Number: NCT00601250
• Other Study ID Numbers: 1218.17; 2007-002457-24 ( EudraCT Number: EudraCT )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
• Original Responsible Party: Not Provided
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

• PRS Account: Boehringer Ingelheim
• Verification Date: December 2013