Empagliflozin Add on to Linagliptin Study in Japanese Patient With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Linagliptin; Empagliflozin placebo + linagliptin placebo low dose; Empagliflozin + linagliptin low dose; Linagliptin placebo; Empagliflozin + linagliptin high dose; Empa + lina highdose placebo
Intervention description: Matching placebo empagliflozin + linagliptin; tablet; Matching placebo linagliptin; tablet
Intervention MeSH terms: Empagliflozin; Linagliptin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 275.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      This trial will compare the use of fixed dose combination of empagliflozin and linagliptin to
      linagliptin alone in patient with type 2 diabetes mellitus
    

Eligibility criteria:

        Inclusion criteria:

          1. Diagnosis of Type-2 Diabetes Mellitus (T2DM) prior to informed consent

          2. Male and female patients on diet and exercise regimen for at least 12 weeks prior to
             informed consent who are:

               -  1 drug-naïve, defined as no antidiabetic drugs for at least 12 weeks prior to
                  informed consent, or

               -  2 pre-treated with one oral antidiabetic drug (for sulfonylurea, with up to half
                  of the maximum approved dose) on stable dosage for at least 12 weeks prior to
                  informed consent (for thiazolidinedione, therapy has to be unchanged for at least
                  18 weeks prior to the informed consent, for linagliptin 5 mg at least 16 weeks
                  prior to Visit 1). Individual antidiabetic drug (except linagliptin) will have to
                  be discontinued at Visit 1.

          3. HbA1c at Visit 1

               -  1 HbA1c =8.0% and =10.5% for patients who are drug-naïve, or

               -  2 HbA1c =7.5% and =10.5% for patients with one oral antidiabetic drug (except
                  linagliptin), or

               -  3 HbA1c =7.5% and =10.0% for patients with linagliptin 5 mg

          4. HbA1c =7.5% and =10.0% at Visit 4 for randomisation into the double-blind treatment
             period. Patient who are pre-treated with linagliptin 5 mg for 16 weeks or more prior
             to Visit 1 and meet the criteria of HbA1c can directly move on to the run-in (Visit
             4).

          5. Age =20 years at informed consent

          6. BMI =40.0 kg/m2 at Visit 1 (screening)

          7. Signed and dated written informed consent by date of Visit 1 in accordance with Good
             Clinical Practice (GCP) and local legislation

        Exclusion criteria:

          1. Uncontrolled hyperglycemia with a glucose level >270 mg/dL (>15.0 mmol/L) after an
             overnight fast during the open-label stabilisation period (from Visit 2 to Visit 4)
             and run-in period (from Visit 4 to Visit 5) , confirmed by a second measurement (not
             on the same day and done either at the central or at local laboratory).

          2. Acute coronary syndrome (ST-elevation myocardial infarction [STEMI], non-STEMI, and
             unstable angina pectoris), stroke or transient ischemic attack within 12 weeks prior
             to informed consent

          3. Indication of liver disease, defined by serum levels of either alanine
             aminotransferase (ALT Serum glutamic pyruvate transaminase [SGPT]), aspartate
             aminotransferase (AST, Serum glutamic oxaloacetic transaminase [SGOT]), or alkaline
             phosphatase (ALP) above 3 x upper limit of normal (ULN) as determined during
             screening, open-label stabilisation period and/or run-in period

          4. Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <45
             mL/min/1.73 m2 (MDRD formula) as determined during screening, open-label stabilisation
             period and/or run-in period

          5. Known hereditary galactose intolerance

          6. Known contraindications to linagliptin and empagliflozin according to the Japanese
             label

          7. Any previous (within 2 years prior to informed consent) or planned bariatric surgery
             (or any other weight loss surgery) or other gastrointestinal surgery that induce
             chronic malabsorption

          8. Medical history of cancer (except for resected non-invasive basal cell or squamous
             carcinoma) and/or treatment for cancer within the last 5 years

          9. Known blood dyscrasias or any disorders causing haemolysis or unstable red blood cell
             (RBC) count (e.g. malaria, babesiosis, haemolytic anaemia).

         10. Treatment with insulin, Glucagon-like peptide-1 agonists, within 12 weeks prior to
             informed consent

         11. Treatment with anti-obesity drugs within 12 weeks 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

         12. Current treatment with systemic steroids (other than inhaled or topical steroids) at
             informed consent or change in dosage of thyroid hormones within 6 weeks prior to
             informed consent or any other uncontrolled endocrine disorder except T2DM

         13. Pre-menopausal women (last menstruation =1 year prior to informed consent) who:

               -  1 are nursing or pregnant or

               -  2 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. Acceptable methods of birth control include tubal ligation, intra
                  uterine devices/systems, oral contraceptives, complete sexual abstinence, double
                  barrier method and vasectomised partner

         14. Known or suspected allergy or hypersensitivity to trial products or related products
             (e.g., Dipeptidyl-peptidase-4 inhibitors or Sodium-glucose co-transporter-2
             inhibitors)

         15. Alcohol or drug abuse within the 12 weeks prior to informed consent that would
             interfere with trial participation or any ongoing condition leading to a decreased
             compliance to trial procedures or trial drug intake, by the judgment of the
             investigator

         16. Intake of an investigational drug in another trial within 30 days prior to Visit 1 or
             participation in the follow-up period of another trial (participation in observational
             studies is permitted)

         17. Any other clinical condition that, in the opinion of the investigator, would
             jeopardize patient's safety while participating in this clinical trial