Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Japanese Patients With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: empagliflozin 10 mg + linagliptin 5 mg; empagliflozin 10 mg; empagliflozin 25 mg + linagliptin 5 mg; empagliflozin 25 mg; Placebo
Intervention description: empagliflozin low dose + linagliptin once daily; empagliflozin low dose once daily; empagliflozin high dose + linagliptin once daily; empagliflozin high dose once daily
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: 880.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      Two independent study parts (i.e. Part A and Part B) are included in this trial. Part A will
      evaluate empagliflozin 10 mg + linagliptin and Part B will evaluate empagliflozin 25 mg +
      linagliptin. All analyses will be carried out separately for these study parts. The objective
      of Part A is to investigate the efficacy, safety and tolerability of the fixed dose
      combination (FDC) of empagliflozin 10 mg / linagliptin 5 mg compared with empagliflozin 10 mg
      plus FDC matching placebo administered orally once daily for 24 weeks in Japanese patients
      with T2DM (Type 2 Diabetes Mellitus) who have insufficient glycaemic control after 16 weeks
      of treatment with empagliflozin 10 mg alone once daily. The study is designed to show
      superiority of the FDC of empagliflozin 10 mg / linagliptin 5 mg over empagliflozin 10 mg
      plus FDC matching placebo after 24 weeks of treatment. The objective of Part B is to
      investigate the efficacy, safety and tolerability of the FDC of empagliflozin 25 mg /
      linagliptin 5 mg compared with empagliflozin 25 mg plus FDC matching placebo administered
      orally once daily for 24 weeks in Japanese patients with T2DM who have insufficient glycaemic
      control after 16 weeks of treatment with empagliflozin 25 mg alone once daily. The study is
      designed to show superiority of the FDC of empagliflozin 25 mg / linagliptin 5 mg over
      empagliflozin 25 mg plus FDC matching placebo after 24 weeks of treatment. The 24 week
      treatment period will be followed by a 28 week extension treatment period to evaluate further
      efficacy and safety up to 52 weeks.
    

Eligibility criteria:

        Inclusion criteria:

          -  Diagnosis of type 2 diabetes prior to informed consent

          -  Male and female patients on diet and exercise regimen for at least 12 weeks prior to
             informed consent who are:

               -  drug-naïve, defined as no antidiabetic drugs for at least 12 weeks prior to
                  informed consent or,

               -  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 the
                  informed consent (for thiazolidinedione, therapy has to be unchanged for at least
                  18 weeks prior to the informed consent). Individual antidiabetic drug will have
                  to be discontinued at Visit 1.

          -  haemoglobin A1c (HbA1c) at Visit 1 (screening)

               -  for patients without antidiabetic therapy : HbA1c >=8.0 to =<10.5%

               -  for patients with one oral antidiabetic drug : HbA1c >=7.5 to =<10.5%

          -  HbA1c >=7.5 to =<10.0% at Visit 4 for randomisation into the double blind treatment
             period

        Exclusion criteria:

          -  Uncontrolled hyperglycaemia with a glucose level >270 mg/dL (>15.0 mmol/L) during the
             open label stabilisation period and placebo run in period

          -  Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <45
             mL/min/1.73m2 (modification of diet in renal disease (MDRD) formula)

          -  Acute coronary syndrome, stroke or transient ischemic attack (TIA) within 12 weeks
             prior to informed consent

          -  Indication of liver disease, defined by serum levels of either alanine transaminase
             (ALT), aspartate transaminase (AST), or alkaline phosphatase (ALP) above 3 x upper
             limit of normal (ULN)