Linagliptin Add-on to Insulin Background Therapy
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: placebo; linagliptin; background therapy
Intervention description: insulin with or without metformin
Intervention MeSH terms: Linagliptin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 206.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To evaluate the efficacy and safety of linagliptin compared to placebo when added on to
      insulin therapy alone or in combination with metformin in Chinese patients with type 2
      diabetes mellitus with insufficient glycaemic control
    

Eligibility criteria:

        Inclusion criteria:

          -  Diagnosis of type 2 diabetes mellitus prior to informed consent.

          -  Chinese male or female patients who are pre-treated with insulin alone or in
             combination with metformin:

               -  With maximum insulin dose of <= 1 unit/kg/day. Acceptable basal insulins could be
                  insulin glargin, insulin detemir or NPH (neutral protamin hagedorn) insulin with
                  duration of action up to 24 h; acceptable pre-mixed insulins could be
                  preparations with 25/75 or 30/70 ratio, with once or twice daily posology only.
                  The total insulin dose should not be changed by more than 10% of the baseline
                  value within the 12 weeks prior to randomisation (Visit 3). Both human insulin &
                  insulin analogue are accepted.

               -  If the patient is taking metformin, stable dose (at least 1500 mg daily) must be
                  maintained for at least 12 weeks without dose adjustments prior to randomisation
                  (Visit 3).

          -  HbA1c fulfills the following criteria: >= 7.5 % to <= 10.0 % at Visit 1.

          -  Age >= 18 years at Visit 1.

          -  BMI <= 45 kg/m2 (Body Mass Index) at Visit 1.

          -  Women of childbearing potential must be ready and able to use highly effective methods
             of birth control per ICH (International Conference on Harmonisation) M3 (R2) that
             result in a low failure rate of less than 1% per year when used consistently and
             correctly. A list of contraception methods meeting these criteria is provided in the
             patient information.

               -  A woman is considered of childbearing potential (WOCBP), i.e. fertile, following
                  menarche and until becoming post-menopausal unless permanently sterile.

               -  Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and
                  bilateral oophorectomy.

          -  Signed and dated written informed consent by date of Visit 1 in accordance with
             ICH-GCP (Good Clinical Practice) and local legislation

        Exclusion criteria:

          -  Uncontrolled hyperglycaemic with a glucose level >240 mg/dl (>13.3 mmol/L) after an
             overnight fast during placebo run-in and confirmed by a second measurement (not on the
             same day).

          -  Any other antidiabetic drug within 3 months prior to informed consent except those
             defined as background treatment via inclusion criterion 2.

          -  Acute coronary syndrome (non-STEMI (ST Segment Elevation Myocardial Infarction), STEMI
             and unstable angina pectoris), stroke or TIA (Transient ischemic attack) within 3
             months prior to informed consent.

          -  Indication of liver disease, defined by serum levels of either ALT (Alanine
             aminotransferase) (SGPT (serum glutamic pyruvate transaminase )), AST (Aspartate
             aminotransferase) (SGOT (serum glutamic-oxaloacetic transaminase)), or alkaline
             phosphatase above 3 × upper limit of normal (ULN (upper limit of normal)) as
             determined during screening and/or run-in phase.

          -  Any contraindications to metformin according to the local label for those patients
             that enter the study with metformin therapy as provided in ISF (Investigator Site
             File).

          -  Bariatric surgery within the past two years and other gastrointestinal surgeries that
             induce chronic malabsorption.

          -  Medical history of cancer (except for basal cell carcinoma) and/or treatment for
             cancer within the last 5 years.

          -  Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cell (e.g.
             malaria, babesiosis, haemolytic anemia).

          -  Known hypersensitivity or allergy to the investigational product or its recipients.

          -  Treatment with anti-obesity drugs 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.

          -  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 T2DM (Type 2 diabetes mellitus).

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial.

          -  Alcohol or drug abuse within the 3 months prior to informed consent that would
             interfere with trial participation or any ongoing condition leading to a decreased
             compliance to study procedures or study drug intake in the opinion of the
             investigator.

          -  Participation in another trial with an investigational drug within 2 months prior to
             informed consent or previous enrolment in this trial.

          -  Any other clinical condition that would jeopardize patient's safety while
             participating in this clinical trial in the opinion of the investigator.