Safety and Efficacy in Type 2 Diabetic Patients With Severe Chronic Renal Impairment, 5 mg BI 1356 (Linagliptin) vs. Placebo, Insulin Background Inclusive

Safety in Type 2 Diabetic Patients With Severe Chronic Renal Impairment, 5 mg BI 1356 vs. Placebo, DB, Parallel Group, Randomized, Insulin Background Inclusive

to determine safety, efficacy and tolerability of BI 1356 versus placebo

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: BI 1356; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, SA, Australia
    • 1218.43.61005 Boehringer Ingelheim Investigational Site
  • Herston, QLD, Australia
    • 1218.43.61002 Boehringer Ingelheim Investigational Site
  • New South Wales
    • Gosford, New South Wales, Australia
      • 1218.43.61009 Boehringer Ingelheim Investigational Site
  • Queensland
    • Auchenflower, Queensland, Australia
      • 1218.43.61010 Boehringer Ingelheim Investigational Site
    • Kippa Ring, Queensland, Australia
      • 1218.43.61006 Boehringer Ingelheim Investigational Site
  • Victoria
    • Reservoir, Victoria, Australia
      • 1218.43.61007 Boehringer Ingelheim Investigational Site
    • Richmond, Victoria, Australia
      • 1218.43.61011 Boehringer Ingelheim Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • 1218.43.85201 Boehringer Ingelheim Investigational Site
  • New Territories, Hong Kong
    • 1218.43.85203 Boehringer Ingelheim Investigational Site
• Israel
  • Afula, Israel
    • 1218.43.97008 Boehringer Ingelheim Investigational Site
  • Ashkelon, Israel
    • 1218.43.97005 Boehringer Ingelheim Investigational Site
  • Haifa, Israel
    • 1218.43.97003 Boehringer Ingelheim Investigational Site
  • Jerusalem, Israel
    • 1218.43.97004 Boehringer Ingelheim Investigational Site
  • Jerusalem, Israel
    • 1218.43.97009 Boehringer Ingelheim Investigational Site
  • Kfar Saba, Israel
    • 1218.43.97002 Boehringer Ingelheim Investigational Site
  • Nahariya, Israel
    • 1218.43.97007 Boehringer Ingelheim Investigational Site
  • Safed, Israel
    • 1218.43.97001 Boehringer Ingelheim Investigational Site
  • Tel Aviv, Israel
    • 1218.43.97006 Boehringer Ingelheim Investigational Site
• New Zealand
  • Auckland, New Zealand
    • 1218.43.64001 Boehringer Ingelheim Investigational Site
  • Christchurch, New Zealand
    • 1218.43.64003 Boehringer Ingelheim Investigational Site
  • Takpuna, New Zealand
    • 1218.43.64004 Boehringer Ingelheim Investigational Site
  • Tauranga, New Zealand
    • 1218.43.64002 Boehringer Ingelheim Investigational Site
• Ukraine
  • Kharkiv, Ukraine
    • 1218.43.38004 Boehringer Ingelheim Investigational Site
  • Kharkov, Ukraine
    • 1218.43.38003 Boehringer Ingelheim Investigational Site
  • Kharkov, Ukraine
    • 1218.43.38006 Boehringer Ingelheim Investigational Site
  • Kiev, Ukraine
    • 1218.43.38005 Boehringer Ingelheim Investigational Site
  • Lugansk, Ukraine
    • 1218.43.38007 Boehringer Ingelheim Investigational Site
  • Ternopil, Ukraine
    • 1218.43.38008 Boehringer Ingelheim Investigational Site
  • Zaporizhzhya, Ukraine
    • 1218.43.38002 Boehringer Ingelheim Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States
      • 1218.43.10027 Boehringer Ingelheim Investigational Site
  • California
    • Chula Vista, California, United States
      • 1218.43.10011 Boehringer Ingelheim Investigational Site
    • Riverside, California, United States
      • 1218.43.10006 Boehringer Ingelheim Investigational Site
    • Whittier, California, United States
      • 1218.43.10021 Boehringer Ingelheim Investigational Site
  • Florida
    • Pembroke Pines, Florida, United States
      • 1218.43.10013 Boehringer Ingelheim Investigational Site
    • West Palm Beach, Florida, United States
      • 1218.43.10009 Boehringer Ingelheim Investigational Site
  • Georgia
    • Decatur, Georgia, United States
      • 1218.43.10018 Boehringer Ingelheim Investigational Site
  • Illinois
    • Chicago, Illinois, United States
      • 1218.43.10022 Boehringer Ingelheim Investigational Site
  • Louisiana
    • Shreveport, Louisiana, United States
      • 1218.43.10015 Boehringer Ingelheim Investigational Site
  • Missouri
    • Kansas City, Missouri, United States
      • 1218.43.10016 Boehringer Ingelheim Investigational Site
  • New York
    • Bronx, New York, United States
      • 1218.43.10004 Boehringer Ingelheim Investigational Site
    • Great Neck, New York, United States
      • 1218.43.10003 Boehringer Ingelheim Investigational Site
  • North Carolina
    • Winston-Salem, North Carolina, United States
      • 1218.43.10020 Boehringer Ingelheim Investigational Site
  • Ohio
    • Delaware, Ohio, United States
      • 1218.43.10019 Boehringer Ingelheim Investigational Site
    • Mentor, Ohio, United States
      • 1218.43.10008 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States
      • 1218.43.10005 Boehringer Ingelheim Investigational Site
    • Carlisle, Pennsylvania, United States
      • 1218.43.10007 Boehringer Ingelheim Investigational Site
  • Rhode Island
    • Providence, Rhode Island, United States
      • 1218.43.10001 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Aiken, South Carolina, United States
      • 1218.43.10025 Boehringer Ingelheim Investigational Site
  • Texas
    • Austin, Texas, United States
      • 1218.43.10023 Boehringer Ingelheim Investigational Site
    • Austin, Texas, United States
      • 1218.43.10024 Boehringer Ingelheim Investigational Site
    • Dallas, Texas, United States
      • 1218.43.10014 Boehringer Ingelheim Investigational Site
    • Lufkin, Texas, United States
      • 1218.43.10017 Boehringer Ingelheim Investigational Site
  • Washington
    • Tacoma, Washington, United States
      • 1218.43.10010 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Male and female patients with type 2 diabetes and with glomerular filtration rate (GFR) <30 ml/min, who are not on chronic dialysis.
• Insufficient glycemic control (hemoglobin A1c (HbA1c) between 7.0% and 10.0%)
• Age 18 or over and not older than 80 years

Exclusion criteria:

• Treatment with any other anti diabetic drug other than insulin and/or sulphonylurea within 3 months prior to informed consent
• Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent
• Unstable or acute congestive heart failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 1356; patient to receive a tablet containing BI 1356 once daily	Drug: BI 1356; BI 1356 dosed once daily
Placebo Comparator: placebo; patient to receive a tablet identical to BI 1356 once daily	Drug: placebo; placebo matching BI 1356 taken once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c Change From Baseline at Week 12	HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline continuous HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c Change From Baseline at Week 52	HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 52 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.	Baseline and Week 52
HbA1c Change From Baseline at Week 18	HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.	Baseline and Week 18
HbA1c Change From Baseline at Week 24	HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.	Baseline and Week 24
HbA1c Change From Baseline at Week 30	HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 30 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.	Baseline and Week 30
HbA1c Change From Baseline at Week 36	HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 36 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.	Baseline and Week 36
HbA1c Change From Baseline at Week 42	HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 42 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.	Baseline and Week 42
HbA1c Change From Baseline at Week 48	HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 48 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication.	Baseline and Week 48
The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <6.5% After 52 Weeks of Treatment	The percentage of patients with an HbA1c value below 6.5% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). Analysis was only performed on patients with baseline HbA1c>=6.5%	Baseline and Week 52
The Occurrence of a Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 52 Weeks of Treatment	The percentage of patients with an HbA1c value below 7.0% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). Analysis was only performed on patients with baseline HbA1c>=7%.	Baseline and Week 52
Percentage of Patients With HbA1c Lowering by 0.5% at Week 52	The percentage of patients with an HbA1c reduction from baseline >=0.5% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF).	Baseline and Week 52
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 continuous baseline FPG , creatinine clearance , HbA1c and background of anti diabetic drugs	Baseline and Week 12
FPG Change From Baseline at Week 18	Model includes treatment, continuous baseline FPG , creatinine clearance , HbA1c and background of anti diabetic drugs	Baseline and Week 18
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 continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs	Baseline and Week 24
FPG Change From Baseline at Week 30	This change from baseline reflects the week 30 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs	Baseline and Week 30
FPG Change From Baseline at Week 36	This change from baseline reflects the week 36 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs	Baseline and Week 36
FPG Change From Baseline at Week 42	This change from baseline reflects the week 42 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs	Baseline and Week 42
FPG Change From Baseline at Week 48	This change from baseline reflects the week 48 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs	Baseline and Week 48
FPG Change From Baseline at week52	This change from baseline reflects the week 52 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs	Baseline and Week 52
Change From Baseline in Antidiabetic Background Therapy Dose at 52 Weeks Compared to Baseline and Over Time	Number of patients with at least one change in daily dose, determined by at least a 10% increase in insulin.	Baseline and Week 52
Clinically Relevant Drug-related Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG	Clinically relevant drug-related abnormalities for blood chemistry, pulse rate, laboratory parameters and ECG. New abnormal findings or worsening of baseline conditions were reported as adverse events.	first administration of randomised treatment to ....

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• McGill JB, Barnett AH, Lewin AJ, Patel S, Neubacher D, von Eynatten M, Woerle HJ. Linagliptin added to sulphonylurea in uncontrolled type 2 diabetes patients with moderate-to-severe renal impairment. Diab Vasc Dis Res. 2014 Jan;11(1):34-40. doi: 10.1177/1479164113507068. Epub 2013 Oct 29.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: December 1, 2008
• First Submitted That Met QC Criteria: December 1, 2008
• First Posted (Estimate): December 2, 2008

Study Record Updates

• Last Update Posted (Estimate): May 20, 2014
• Last Update Submitted That Met QC Criteria: May 15, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Renal Insufficiency; Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin
• Other Study ID Numbers: 1218.43; 2008-001569-27 (EudraCT Number: EudraCT)