Linagliptin 2.5 mg Twice Daily Versus 5 mg Once Daily as add-on Therapy to Twice Daily Metformin in Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01012037
First received: November 10, 2009
Last updated: June 17, 2014
Last verified: December 2013
  Purpose

The objective of the study is to investigate the efficacy and safety of linagliptin 2.5 mg twice daily compared to 5 mg once daily compared to placebo given orally for 12 weeks as add-on therapy to metformin in patients with type 2 diabetes mellitus with insufficient glycaemic control. It is planned to show non-inferiority of linagliptin 2.5 mg twice daily compared to 5 mg once daily and each treatment's superiority over placebo.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: linagliptin low dose
Drug: placebo
Drug: linagliptin medium dose
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 12 Week Randomised Double-blind BI 1356 2.5 mg Bid vs 5 mg qd add-on to Metformin

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • HbA1c Change From Baseline at 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. Treatment means are adjusted for baseline HbA1c and use of prior oral antidiabetics (OADs) in addition to background metformin.


Secondary Outcome Measures:
  • HbA1c Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
    Mixed model includes treatment, baseline HbA1c, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.

  • HbA1c Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    Mixed model includes treatment, baseline HbA1c, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.

  • FPG Change From Baseline at Week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    Change from baseline reflects the Week 12 FPG minus the baseline FPG. Treatment means are adjusted for baseline HbA1c, baseline fasting plasma glucose and use of prior oral antidiabetics (OADs) in addition to background metformin.

  • FPG Change From Baseline at Week 6 From Mixed Model Repeated Measures (MMRM) Analysis [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
    Mixed model includes treatment, baseline HbA1c, baseline FPG, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.

  • FPG Change From Baseline at Week 12 From Mixed Model Repeated Measures (MMRM) Analysis [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    Mixed model includes treatment, baseline HbA1c, baseline FPG, use of prior oral antidiabetics (OADs) in addition to background metformin, week repeated within patient, week by treatment interaction.

  • Percentage of Patients With HbA1c Lowering by 0.5% or More at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Percentage of patients with HbA1c lowering by at least 0.5% after 12 weeks. The analysis was performed on the full analysis set (FAS) using NCF.

  • Percentage of Patients With Rescue Therapy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Percentage of patients with rescue therapy at Week 12. The analysis was performed on the full analysis set (FAS) using OC.

  • The Occurrence of a Treat to Target Efficacy Response (HbA1c <7.0%) After 12 Weeks of Treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Percentage of those patients with baseline HbA1c >= 7.0% who had HbA1c < 7% at Week 12. The analysis was performed on the full analysis set (FAS) using NCF.

  • The Occurrence of a Treat to Target Efficacy Response (HbA1c <6.5 %) After 12 Weeks of Treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Percentage of those patients with baseline HbA1c >= 6.5% who had HbA1c < 6.5% at Week 12. The analysis was performed on the full analysis set (FAS) using NCF.


Enrollment: 491
Study Start Date: November 2009
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: linagliptin low dose
linagliptin low dose twice daily
Drug: linagliptin low dose
patient to receive tablets containing low dose linagliptin twice daily
Placebo Comparator: placebo
placebo matching linagliptin
Drug: placebo
patient to receive placebo tablet(s) matching linagliptin
Experimental: linagliptin medium dose
linagliptin medium dose once daily
Drug: linagliptin medium dose
patient to receive a tablet containing medium dose linagliptin once daily

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Diagnosis of type 2 diabetes mellitus.
  2. Current treatment with metformin alone (>/= 1500 mg or maximally tolerated dose) or metformin plus 1 other antidiabetic drug. Metformin must be administered in twice daily dosing regimen. Patients taking metformin three times daily can be included if posology is switched to twice daily and total daily dose is maintained.
  3. Glycosylated haemoglobin (HbA1c) is between 7.0% - 10.0%.
  4. Body Mass Index (BMI) </=45 kg/m2.

Exclusion criteria

  1. Treatment with extended release metformin.
  2. Uncontrolled hyperglycaemia (fasting plasma glucose > 240 mg/dL or 13.3 mmol/L).
  3. Myocardial infarction (MI), stroke or transient ischaemic attack (TIA) within 6 months prior to informed consent.
  4. Impaired hepatic or renal function, or gastric bypass surgery.
  5. Treatment with glitazones, glucagon like peptide-1 (GLP-1) analogues/mimetics, antiobesity agents, or insulin within 3 months of informed consent.
  6. Current treatment with systemic steroids or change in dosage of thyroid hormones.
  7. Alcohol or drug abuse within 3 months of informed consent.
  8. Participation in another trial with investigational drug within 2 months prior to informed consent.
  9. Pre-menopausal women who are nursing, pregnant or not practicing an acceptable method of birth control.
  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: NCT01012037

  Show 84 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01012037     History of Changes
Other Study ID Numbers: 1218.62, 2009-013549-27
Study First Received: November 10, 2009
Results First Received: September 21, 2011
Last Updated: June 17, 2014
Health Authority: Belgium: Federal Agency for Medicinal and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
India: Drugs Controller General of India
Italy: Ethics Committee
Malaysia: Ministry of Health
Netherlands: Central Committee Research Involving Human Subjects
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Ministry of Health

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
BI 1356
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014