Linagliptin and Metformin Versus Linagliptin in Newly Diagnosed, Untreated Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01512979
First received: January 16, 2012
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

The purpose of this trial is to determine whether a initial combination of linagliptin and metformin compared to linagliptin alone for 24 weeks is effective in newly diagnosed, treatment-naïve patients with Type 2 Diabetes.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: metformin
Drug: linagliptin
Drug: metformin placebo
Phase 4

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 24-week, Randomized, Double-blind, Active-controlled, Parallel Group Trial to Assess the Superiority of Oral Linagliptin and Metformin Compared to Linagliptin Monotherapy in Newly Diagnosed, Treatment-naïve, Uncontrolled Type 2 Diabetes Mellitus Patients

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline in HbA1c After 24 Weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. The change from baseline is the Week 24 HbA1c minus the baseline HbA1c. Means are adjusted for treatment and continuous baseline HbA1c


Secondary Outcome Measures:
  • Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    The change from baseline is the FPG after 24 weeks minus the baseline FPG. Means are adjusted for treatment, continuous baseline HbA1c and continuous baseline fasting plasma glucose.

  • Change From Baseline in HbA1c by Visit Over Time [ Time Frame: Baseline, 6, 12, 18 and 24 weeks ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. The change from baseline is the HbA1c over time minus the baseline HbA1c. The model includes treatment, continuous baseline HbA1c in addition to week repeated within patient, week by baseline HbA1c interaction and week by treatment interaction.

  • Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment) [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved HbA1c lowering by at least 0.5% after 24 weeks of treatment.The model includes treatment, and continuous baseline HbA1c.

  • Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 1.0% After 24 Weeks of Treatment) [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved HbA1c lowering by at least 1.0% after 24 weeks of treatment. The model includes treatment, and continuous baseline HbA1c.

  • Occurrence of Treat to Target Efficacy Response (HbA1c <7.0%) After 24 Weeks of Treatment [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved HbA1c below 7.0% after 24 weeks of treatment. The model includes treatment, and continuous baseline HbA1c.

  • Change From Baseline in FPG by Visit Over Time [ Time Frame: Baseline, 6, 12, 18 and 24 weeks ] [ Designated as safety issue: No ]
    The change from baseline is the FPG over time minus the baseline FPG. Means are adjusted for treatment, continuous baseline HbA1c, continuous baseline FPG in addition to week repeated within patient, week by baseline FPG interaction and week by treatment interaction.


Enrollment: 316
Study Start Date: January 2012
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: linagliptin
patients receive linagliptin tablet once daily
Drug: linagliptin
5 mg daily
Drug: metformin placebo
4 tablets daily
Experimental: linagliptin plus metformin
patients receive linagliptin tablet once daily and metformin tablets twice daily
Drug: metformin
1000 mg to 2000 mg per day
Drug: linagliptin
5 mg daily
Drug: metformin placebo
0 to 2 tablets daily

  Eligibility

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

Inclusion criteria:

  1. Patients must sign and date an Informed Consent consistent with International Conference on Harmonisation / Good Clinical Practice guidelines and local regulations prior to any evaluation and participation in the trial.
  2. Male and female patients, 18 years of age or older at Visit 1 (Screen), with newly diagnosed (less than 12 months prior to Screen) Type 2 Diabetes Mellitus.
  3. Patients who are treatment-naïve, defined as absence of any oral antidiabetic therapy, injectable glucagon-like peptide-1 agonist/analogue, or insulin, and uncontrolled for the 12 weeks prior to randomisation.
  4. Patients must have an glycated (or glycosylated) haemoglobin (HbA1c) between 8.5% [69 millimoles per mole (mmol/mol)] and 12.0% (108 mmol/mol) at Visit 1 (Screen).
  5. Patients must have a Body Mass Index (BMI) of 45 kg/m2 or less at Visit 1 (Screen).
  6. In the investigators opinion, patients must be reliable, honest, compliant, and agree to cooperate with all planned future trial evaluations as explained in detail during the informed consent process and to be able to perform them.

Exclusion criteria:

Patients with, who are, who have, or who have had:

  1. Acute coronary syndrome (non-ST Elevation Myocardial Infarction (STEMI), STEMI, and unstable angina pectoris), stroke or transient ischemic attack within 3 months prior to informed consent.
  2. Indication of liver disease determined during Screen and/or Run-In Period, defined by a serum level above 3 times the upper limit of normal (ULN) in any of the following: alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase. Gilbert-Meulengracht syndrome (also known as conjugated hyperbilirubinemia, constitutional hepatic dysfunction, or familial nonhemolytic jaundice) will be permitted.
  3. Impaired renal function, defined as calculated creatinine clearance of less than 60 milliliters per minute (< 60 mL/min), by the Cockcroft-Gault Equation, as determined during Screen and/or Run-In Period.
  4. Bariatric, gastric bypass, and other gastrointestinal surgeries (including all types of gastric banding and/or LapBand) within the past two years.
  5. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.
  6. Medical history of pancreatitis.
  7. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (e.g., malaria, babesiosis, haemolytic anaemia).
  8. Any contraindication to metformin and/or linagliptin therapies, according to local labels.
  9. Treatment with anti-obesity drugs, including over-the-counter drugs such as Alli (orlistat), 3 months prior to informed consent or any other treatment at the time of screening (i.e., surgery, aggressive diet regimen, etc.) leading to unstable body weight.
  10. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except Type 2 Diabetes Mellitus.
  11. Pre-menopausal women (last menstruation of 1 year or less prior to informed consent) who are nursing or pregnant, 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 trial and do not agree to submit to periodic pregnancy testing during participation in the trial.

    Note: Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable, intra-vaginal, or injectable contraceptives, Essure micro-inserts placed more than six months prior to Screen Visit, complete sexual abstinence (if acceptable by local authorities), double barrier method (e.g., diaphragm or condom and spermicide), and vasectomised partner.

  12. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance to trial procedures or study medication intake in the opinion of the investigator.
  13. Participation in another trial with an investigational drug within 2 months prior to informed consent.
  14. Any other clinical condition that would jeopardize patient safety while participating in this clinical trial in the opinion of the Investigator.
  15. Inability to commit to regular overnight fasting of at least 10 hours duration and attendance to study site visits between 07:00 and 11:00 ante meridiem (a.m.).
  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: NCT01512979

  Hide Study Locations
Locations
United States, Arizona
1218.83.11002 Boehringer Ingelheim Investigational Site
Phoenix, Arizona, United States
United States, Arkansas
1218.83.11036 Boehringer Ingelheim Investigational Site
Little Rock, Arkansas, United States
United States, California
1218.83.11011 Boehringer Ingelheim Investigational Site
Chino, California, United States
1218.83.11001 Boehringer Ingelheim Investigational Site
Huntington Beach, California, United States
1218.83.11019 Boehringer Ingelheim Investigational Site
Huntington Park, California, United States
1218.83.11015 Boehringer Ingelheim Investigational Site
Lomita, California, United States
1218.83.11023 Boehringer Ingelheim Investigational Site
Norwalk, California, United States
1218.83.11014 Boehringer Ingelheim Investigational Site
Roseville, California, United States
1218.83.11031 Boehringer Ingelheim Investigational Site
San Diego, California, United States
United States, Florida
1218.83.11022 Boehringer Ingelheim Investigational Site
Fort Lauderdale, Florida, United States
1218.83.11025 Boehringer Ingelheim Investigational Site
Orlando, Florida, United States
1218.83.11033 Boehringer Ingelheim Investigational Site
Sanford, Florida, United States
United States, Georgia
1218.83.11029 Boehringer Ingelheim Investigational Site
Oakwood, Georgia, United States
United States, Kentucky
1218.83.11026 Boehringer Ingelheim Investigational Site
Owensboro, Kentucky, United States
United States, Maryland
1218.83.11008 Boehringer Ingelheim Investigational Site
Elkton, Maryland, United States
United States, Nebraska
1218.83.11027 Boehringer Ingelheim Investigational Site
Freemont, Nebraska, United States
United States, New Jersey
1218.83.11005 Boehringer Ingelheim Investigational Site
Edison, New Jersey, United States
United States, North Carolina
1218.83.11013 Boehringer Ingelheim Investigational Site
Jacksonville, North Carolina, United States
1218.83.11028 Boehringer Ingelheim Investigational Site
Salisbury, North Carolina, United States
1218.83.11009 Boehringer Ingelheim Investigational Site
Shelby, North Carolina, United States
United States, Ohio
1218.83.11003 Boehringer Ingelheim Investigational Site
Franklin, Ohio, United States
1218.83.11024 Boehringer Ingelheim Investigational Site
Gallipolis, Ohio, United States
United States, South Carolina
1218.83.11018 Boehringer Ingelheim Investigational Site
Columbia, South Carolina, United States
United States, Tennessee
1218.83.11004 Boehringer Ingelheim Investigational Site
Bristol, Tennessee, United States
1218.83.11017 Boehringer Ingelheim Investigational Site
Chattanooga, Tennessee, United States
United States, Texas
1218.83.11032 Boehringer Ingelheim Investigational Site
Grand Prairie, Texas, United States
1218.83.11030 Boehringer Ingelheim Investigational Site
Houston, Texas, United States
1218.83.11034 Boehringer Ingelheim Investigational Site
San Antonio, Texas, United States
1218.83.11021 Boehringer Ingelheim Investigational Site
Tomball, Texas, United States
Canada, Alberta
1218.83.12011 Boehringer Ingelheim Investigational Site
Calgary, Alberta, Canada
1218.83.12007 Boehringer Ingelheim Investigational Site
Edmonton, Alberta, Canada
1218.83.12001 Boehringer Ingelheim Investigational Site
Red Deer, Alberta, Canada
Canada, Newfoundland and Labrador
1218.83.12002 Boehringer Ingelheim Investigational Site
Paradise, Newfoundland and Labrador, Canada
1218.83.12009 Boehringer Ingelheim Investigational Site
St. John's, Newfoundland and Labrador, Canada
Canada, Ontario
1218.83.12005 Boehringer Ingelheim Investigational Site
Kitchener, Ontario, Canada
1218.83.12006 Boehringer Ingelheim Investigational Site
London, Ontario, Canada
1218.83.12003 Boehringer Ingelheim Investigational Site
Smiths Falls, Ontario, Canada
1218.83.12010 Boehringer Ingelheim Investigational Site
Sudbury, Ontario, Canada
1218.83.12012 Boehringer Ingelheim Investigational Site
Winnipeg, Ontario, Canada
India
1218.83.91003 Boehringer Ingelheim Investigational Site
Bangalore, India
1218.83.91005 Boehringer Ingelheim Investigational Site
Chennai, India
1218.83.91001 Boehringer Ingelheim Investigational Site
Mumbai, India
Israel
1218.83.97005 Boehringer Ingelheim Investigational Site
Haifa, Israel
1218.83.97004 Boehringer Ingelheim Investigational Site
Haifa, Israel
1218.83.97007 Boehringer Ingelheim Investigational Site
Holon, Israel
Malaysia
1218.83.60001 Boehringer Ingelheim Investigational Site
Kelantan, Malaysia
1218.83.60002 Boehringer Ingelheim Investigational Site
Perak, Malaysia
1218.83.60003 Boehringer Ingelheim Investigational Site
Selangor, Malaysia, Malaysia
Mexico
1218.83.52004 Boehringer Ingelheim Investigational Site
Cuautla, Mexico
1218.83.52001 Boehringer Ingelheim Investigational Site
Guadalajara, Mexico
1218.83.52002 Boehringer Ingelheim Investigational Site
Guadalajara, Mexico
1218.83.52005 Boehringer Ingelheim Investigational Site
Merida, Mexico
1218.83.52003 Boehringer Ingelheim Investigational Site
Tampico, Mexico
Philippines
1218.83.63001 Boehringer Ingelheim Investigational Site
Cebu, Philippines
1218.83.63007 Boehringer Ingelheim Investigational Site
Cebu City, Philippines
1218.83.63003 Boehringer Ingelheim Investigational Site
Iloilo, Philippines
1218.83.63008 Boehringer Ingelheim Investigational Site
Iloilo City, Philippines
1218.83.63006 Boehringer Ingelheim Investigational Site
Marikina City, Philippines
1218.83.63002 Boehringer Ingelheim Investigational Site
Marikina City, Philippines
1218.83.63004 Boehringer Ingelheim Investigational Site
Quezon, Philippines
Puerto Rico
1218.83.11037 Boehringer Ingelheim Investigational Site
San Juan, Puerto Rico
Russian Federation
1218.83.07001 Boehringer Ingelheim Investigational Site
Kazan, Russian Federation
1218.83.07002 Boehringer Ingelheim Investigational Site
Petrozavodsk, Russian Federation
1218.83.07004 Boehringer Ingelheim Investigational Site
Samara, Russian Federation
1218.83.07006 Boehringer Ingelheim Investigational Site
Smolensk, Russian Federation
1218.83.07003 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
1218.83.07007 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
1218.83.07005 Boehringer Ingelheim Investigational Site
Yaroslavl, Russian Federation
Sri Lanka
1218.83.94004 Boehringer Ingelheim Investigational Site
Dehiwela, Sri Lanka
1218.83.94002 Boehringer Ingelheim Investigational Site
Galle, Sri Lanka, Sri Lanka
1218.83.94003 Boehringer Ingelheim Investigational Site
Kandy, Sri Lanka
1218.83.94001 Boehringer Ingelheim Investigational Site
Ragama, Sri Lanka
Thailand
1218.83.66003 Boehringer Ingelheim Investigational Site
Bangkok, Thailand
1218.83.66002 Boehringer Ingelheim Investigational Site
Bangkok, Thailand
1218.83.66001 Boehringer Ingelheim Investigational Site
Muang, Khonkaen, Thailand
Ukraine
1218.83.38007 Boehringer Ingelheim Investigational Site
Dnepropetrovsk, Ukraine
1218.83.38001 Boehringer Ingelheim Investigational Site
Ivano-Frankivsk, Ukraine
1218.83.38006 Boehringer Ingelheim Investigational Site
Kharkiv, Ukraine
1218.83.38004 Boehringer Ingelheim Investigational Site
Odessa, Ukraine
1218.83.38008 Boehringer Ingelheim Investigational Site
Vinnitsa, Ukraine
1218.83.38003 Boehringer Ingelheim Investigational Site
Vinnytsya, Ukraine
1218.83.38005 Boehringer Ingelheim Investigational Site
Vinnytsya, Ukraine
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: NCT01512979     History of Changes
Other Study ID Numbers: 1218.83, 2011-004158-24
Study First Received: January 16, 2012
Results First Received: April 8, 2014
Last Updated: May 12, 2014
Health Authority: Canada: Health Canada
India: Drugs Controller General of India
Israel: Israeli Health Ministry Pharmaceutical Administration
Malaysia: Ministry of Health
Mexico: Federal Commission for Sanitary Risks Protection
Philippines: Bureau of Food and Drugs
Russia: Pharmacological Committee, Ministry of Health
Sri Lanka: Ministry of Healthcare and Nutrition
Thailand: Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

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