Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Japanese Patients With Type 2 Diabetes Mellitus

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: empagliflozin 25 mg; Drug: Placebo; Drug: empagliflozin 25 mg + linagliptin 5 mg; Drug: empagliflozin 10 mg; Drug: empagliflozin 10 mg + linagliptin 5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02489968

1275.13

Details and patient eligibility

About

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.

Enrollment: 880 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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880 participants in 4 patient groups

empagliflozin 10 mg + linagliptin 5 mg

Experimental group

Description:

patient to receive a tablet containing low dose empagliflozin and linagliptin once daily

Treatment:

Drug: empagliflozin 10 mg + linagliptin 5 mg

empagliflozin 10 mg

Experimental group

Description:

patient to receive a tablet containing low dose empagliflozin once daily

Treatment:

Drug: Placebo

Drug: empagliflozin 10 mg

empagliflozin 25 mg + linagliptin 5 mg

Experimental group

Description:

patient to receive a tablet containing high dose empagliflozin and linagliptin once daily

Treatment:

Drug: empagliflozin 25 mg + linagliptin 5 mg

empagliflozin 25 mg

Experimental group

Description:

patients to receive a tablet containing high dose empagliflozin once daily

Treatment:

Drug: Placebo

Drug: empagliflozin 25 mg