Efficacy and Safety of Linagliptin in Elderly Patients With Type 2 Diabetes

A Phase III Randomised, Double Blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of Linagliptin (5 mg) Administered Orally Once Daily Over 24 Weeks in Type 2 Diabetic Patients (Age >= 70 Years) With Insufficient Glycaemic Control( HbA1c >= 7.0) Despite Metformin and/or Sulphonylurea and/or Insulin Therapy

The objective of the current study is to investigate the efficacy, safety and tolerability of linagliptin (5 mg / once daily) compared to placebo given for 24 weeks as add-on therapy to stable treatment in elderly patients with T2DM with insufficient glycaemic control

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 241
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Gosford, New South Wales, Australia
      • 1218.63.61005 Boehringer Ingelheim Investigational Site
  • Queensland
    • Herston, Queensland, Australia
      • 1218.63.61006 Boehringer Ingelheim Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia
      • 1218.63.61003 Boehringer Ingelheim Investigational Site
    • Daw Park, South Australia, Australia
      • 1218.63.61002 Boehringer Ingelheim Investigational Site
  • Victoria
    • East Ringwood, Victoria, Australia
      • 1218.63.61007 Boehringer Ingelheim Investigational Site
    • Parkville, Victoria, Australia
      • 1218.63.61001 Boehringer Ingelheim Investigational Site
    • Reservoir, Victoria, Australia
      • 1218.63.61004 Boehringer Ingelheim Investigational Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • 1218.63.10008 Boehringer Ingelheim Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada
      • 1218.63.10003 Boehringer Ingelheim Investigational Site
    • Hawkesbury, Ontario, Canada
      • 1218.63.10005 Boehringer Ingelheim Investigational Site
    • Newmarket, Ontario, Canada
      • 1218.63.10007 Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • 1218.63.10006 Boehringer Ingelheim Investigational Site
  • Quebec
    • Montreal, Quebec, Canada
      • 1218.63.10001 Boehringer Ingelheim Investigational Site
    • St-Romuald, Quebec, Canada
      • 1218.63.10002 Boehringer Ingelheim Investigational Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • 1218.63.10004 Boehringer Ingelheim Investigational Site
• Denmark
  • Aalborg, Denmark
    • 1218.63.45007 Boehringer Ingelheim Investigational Site
  • Aarhus C, Denmark
    • 1218.63.45002 Boehringer Ingelheim Investigational Site
  • Aarhus C, Denmark
    • 1218.63.45003 Boehringer Ingelheim Investigational Site
  • Birkerød, Denmark
    • 1218.63.45001 Boehringer Ingelheim Investigational Site
  • Hellerup, Denmark
    • 1218.63.45008 Boehringer Ingelheim Investigational Site
  • Hillerød, Denmark
    • 1218.63.45006 Boehringer Ingelheim Investigational Site
  • Hvidovre, Denmark
    • 1218.63.45004 Boehringer Ingelheim Investigational Site
  • København NV, Denmark
    • 1218.63.45005 Bispebjerg Hospital
• Netherlands
  • Beek en Donk, Netherlands
    • 1218.63.31008 Boehringer Ingelheim Investigational Site
  • Beerzerveld, Netherlands
    • 1218.63.31007 Boehringer Ingelheim Investigational Site
  • Doetinchem, Netherlands
    • 1218.63.31012 Boehringer Ingelheim Investigational Site
  • Etten-Leur, Netherlands
    • 1218.63.31014 Boehringer Ingelheim Investigational Site
  • Oude Pekela, Netherlands
    • 1218.63.31009 Boehringer Ingelheim Investigational Site
  • Tubbergen, Netherlands
    • 1218.63.31001 Boehringer Ingelheim Investigational Site
• Sweden
  • Göteborg, Sweden
    • 1218.63.46004 Boehringer Ingelheim Investigational Site
  • Järfälla, Sweden
    • 1218.63.46003 Boehringer Ingelheim Investigational Site
  • Malmö, Sweden
    • 1218.63.46001 Boehringer Ingelheim Investigational Site
  • Sundsvall, Sweden
    • 1218.63.46002 Boehringer Ingelheim Investigational Site
  • Uppsala, Sweden
    • 1218.63.46005 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Type 2 diabetes mellitus
2. HbA1c >= 7.0%
3. Age >= 70 years
4. Signed and dated written informed consent

Exclusion criteria:

1. Myocardial infarction, stroke or TIA within 3 months prior to informed consent
2. Impaired hepatic function
3. Treatment with glitazones, GLP-1 analogues, DPP-4 inhibitors or rapid acting or pre-mixed insulins
4. Treatment with anti-obesity drugs

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: linagliptin; patients receive linagliptin 5 mg tablets once daily	Drug: linagliptin; patients receive linagliptin 5 mg tablets once daily
Placebo Comparator: placebo; patients receive placebo tablets matching linagliptin 5 mg once daily	Drug: placebo; patients receive placebo matching linagliptin 5 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 prior use of insulin.	Baseline and week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c Change From Baseline to 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 prior use of insulin.	Baseline and week 6
HbA1c Change From Baseline to 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 prior use of insulin.	Baseline and week 12
HbA1c Change From Baseline to 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 prior use of insulin.	Baseline and week 18
FPG Change From Baseline to 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 prior use of insulin.	Baseline and week 24
FPG Change From Baseline to 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 prior use of insulin, week repeated within patient and week by treatment interaction.	Baseline and week 6
FPG Change From Baseline to 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 prior use of insulin, week repeated within patient and week by treatment interaction.	Baseline and week 12
FPG Change From Baseline to 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 prior use of insulin, week repeated within patient and week by treatment interaction.	Baseline and week 18
Percentage of Patients With HbA1c <7.0% at Week 24	The percentage of patients with an HbA1c value below 7% 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 above 7%. Only patients with baseline HbA1c >= 7%	Baseline and week 24
Percentage of Patients With HbA1c <7.0% at Week 24	The percentage of patients with an HbA1c value below 7% at week 24 were calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.	Baseline and week 24
Percentage of Patients Who Have a HbA1c Lowering by at Least 0.5% at Week 24	The percentage of patients with an HbA1c reduction of ≥0.5% at week 24 from baseline 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
Number of Patients With Rescue Therapy	The use of rescue therapy was planned for patients failing to achieve preset criteria based on glucose levels during the randomised treatment period of the trial	week 24

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Eli Lilly and Company

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.
• Lajara R, Aguilar R, Hehnke U, Woerle HJ, von Eynatten M. Efficacy and safety of linagliptin in subjects with long-standing type 2 diabetes mellitus (>10 years): evidence from pooled data of randomized, double-blind, placebo-controlled, phase III trials. Clin Ther. 2014 Nov 1;36(11):1595-605. doi: 10.1016/j.clinthera.2014.07.020. Epub 2014 Sep 16.
• Barnett AH, Huisman H, Jones R, von Eynatten M, Patel S, Woerle HJ. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Oct 26;382(9902):1413-23. doi: 10.1016/S0140-6736(13)61500-7. Epub 2013 Aug 13.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: March 9, 2010
• First Submitted That Met QC Criteria: March 9, 2010
• First Posted (Estimate): March 10, 2010

Study Record Updates

• Last Update Posted (Estimate): January 29, 2014
• Last Update Submitted That Met QC Criteria: December 11, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; 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: 1218.63; 2009-015255-25 (EudraCT Number: EudraCT)