Safety and Efficacy of Linagliptin in Type-2-diabetes Mellitus Patients With Moderate to Severe Renal Impairment

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01087502
First received: March 15, 2010
Last updated: June 17, 2014
Last verified: May 2014
  Purpose

The objective of the current study is to investigate the efficacy, safety and tolerability of linagliptin (5 mg / once daily) compared to placebo given over 12 weeks in drug naive or previously treated type 2 diabetic patients with moderate to severe renal impairment and insufficient glycaemic control. In addition safety in this patient population with longer term (40 week) treatment in comparison to sulfonylurea drug (glimepiride).


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Glimepiride
Drug: Placebo
Drug: Linagliptin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase III, Randomised, Double-blind, Placebo-controlled Parallel Group Safety and Efficacy Study of Linagliptin (5 mg Administered Orally Once Daily) Over 12 Weeks Followed by a 40 Week Double-blind Extension Period (Placebo Patients Switched to Glimepiride) in Drug Naive or Previously Treated Type 2 Diabetic Patients With Moderate to Severe Renal Impairment and Insufficient Glycaemic Control

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • HbA1c Change From Baseline to Week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    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, renal function impairment and prior use of antidiabetic agents.


Secondary Outcome Measures:
  • HbA1c Change From Baseline Over Time [ Time Frame: Baseline, week 4, week 8, week 12, week 16, week 20, week 24, week 28, week 34, week 40, week 46, week 52 ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. Thus, this change from baseline reflects the HbA1c percent over time minus the baseline HbA1c percent. This outcome measure only provides descriptive statistics without any modelling.

  • Fasting Plasma Glucose (FPG) Change From Baseline to Week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    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.

  • Fasting Plasma Glucose (FPG) Change From Baseline Over Time [ Time Frame: Baseline, week 4, week 8, week 12, week 20, week 24, week 28, week 34, week 40, week 46, week 52 ] [ Designated as safety issue: No ]
    This change from baseline reflects the FPG over time minus the baseline FPG. This outcome measure only provides descriptive statistics without any modelling.

  • Percentage of Patients With HbA1c <7.0% [ Time Frame: Baseline, week 12 and week 52 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 7% at week 12 and week 52 were calculated for each treatment arm. If a patient did not have an HbA1c value at week 12 or 52 respectively, they were considered a failure, so HbA1c above 7%.

  • Percentage of Patients With HbA1c <6.5% [ Time Frame: Baseline, week 12 and week 52 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 6.5% at week 12 and week 52 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 12 or 52 respectively they were considered a failure, so HbA1c above 6.5%.

  • Percentage of Patients Who Have a HbA1c Lowering by at Least 0.5% [ Time Frame: Baseline, week 12 and week 52 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c reduction of ≥0.5% at week 12 and week 52 from baseline was calculated for each treatment arm. If a patient did not have an HbA1c value at week 12 or 52 respectively they were considered a failure, so HbA1c reduction less than 0.5%.

  • Plasma Concentration of Linagliptin at Trough [ Time Frame: Week 12, 24 and 52 ] [ Designated as safety issue: No ]
    Trough levels of concentration of Linagliptin in plasma.


Enrollment: 241
Study Start Date: March 2010
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Linagliptin
52 weeks treatment
Drug: Placebo
Placebo maching Glimepiride 1-4 mg after 12 weeks of treatment
Drug: Linagliptin
5 mg once daily
Placebo Comparator: Placebo
First 12 weeks of treatment
Drug: Placebo
Placebo mach to 5 mg linagliptin first 12 weeks of treatment once daily
Active Comparator: Glimepiride
Placebo patients switch to glimepiride after 12 weeks (40 weeks treatment)
Drug: Glimepiride
1-4 mg daily after 12 weeks
Drug: Placebo
Placebo mach to 5 mg linagliptin once daily after 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Type 2 diabetes mellitus
  2. GFR<60 ml/min
  3. HbA1c >=7.0% to <= 10%
  4. Age >= 18 years
  5. BMI <=45 kg/m2
  6. Signed and dated written informed consent

Exclusion criteria:

  1. Myocardial infarction, stroke or TIA within 3 months prior to informed consent
  2. Renal impairment requiring dialysis
  3. Bariatric surgery
  4. Impaired hepatic function
  5. Treatment with glitazones, GLP-1 analogues, DPP-4 inhibitors
  6. Treatment with anti-obesity drugs
  7. Treatment with SU, glinides and metformin 8 weeks prior to informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01087502

  Show 52 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01087502     History of Changes
Other Study ID Numbers: 1218.64, 2009-016971-31
Study First Received: March 15, 2010
Results First Received: May 17, 2013
Last Updated: June 17, 2014
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Canada: Health Canada
Finland: Finnish Medicines Agency
Israel: Israeli Health Ministry Pharmaceutical Administration
Japan: Ministry of Health, Labor and Welfare
New Zealand: Multi-Regional Ethics Committee
Slovakia: State Institute for Drug Control
Sweden: Medical Products Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Renal Insufficiency
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Kidney Diseases
Urologic Diseases
Glimepiride
BI 1356
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014