A study to evaluate the effect and safety of linagliptin 5 mg administered in combination with empagliflozin 10 mg or 25 mg in patients with type 2 diabetes mellitus whose glucose levels have not been controlled after 16 weeks of treatment with empagliflozin 10 mg or 25 mg and metformin.

• Conditions: Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]; Diabetes mellitus type 2 is the medical condition to be investiagted; MedDRA version: 17.1Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders

• Registration Number: EUCTR2012-002271-34-PT
• Lead Sponsor: nilfarma, Lda.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-03
• Last Update Posted: 19 October 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 690

Inclusion Criteria

Patients treated with metformin for at least 12 weeks
HbA1c = 8.0% (64 mmol/mol) and = 10.5% (91 mmol/mol) at Visit 1 for the 16 week open label treatment period.
HbA1c = 7.0% (53 mmol/mol) and = 10.5 % (91 mmol/mol) at Visit 4 for the 24 week double-blind treatment period.
Body Mass Index (BMI) =45 kg/m2 at Visit 1 (screening)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 517
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 173

Exclusion Criteria

Uncontrolled hyperglycaemia with a glucose level >270 mg/dl (>15.0 mmol/L) after an overnight fast during the open label period (from Visit 2 to Visit 4) and placebo add on run-in period (Visit 4 to Visit 5).
Any other antidiabetic drug within 12 weeks prior to Visit 2 randomization (except metformin background therapy)
Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent
Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) based on Visit 1 or Visit 4 laboratory parameters.
Impaired renal function, defined as eGFR <60 ml/min/1.73 m2 (MDRD formula) as determined during screening (Visit 1) or placebo add on run-in (Visit 4)
Known blood dyscrasias or any disorders causing haemolysis or unstable red blood cell count (e.g. malaria, babesiosis, haemolytic anaemia) due to the short lifespan of the RBC and its impact on HbA1c.
Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) within 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 (other than inhaled or topical steroids) at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other documented uncontrolled endocrine disorder except T2DM.
Pre-menopausal women (last menstruation =1 year prior to informed consent) who are nursing or pregnant.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of the study is to investigate the efficacy, safety and tolerability of the fixed dose combination of empagliflozin 10 mg / linagliptin 5 mg compared with empagliflozin 10 mg alone and placebo and the efficacy and safety of<br>empagliflozin 25 mg / linagliptin 5 mg compared with empagliflozin 25 mg alone and placebo each administered orally once daily over 24 weeks in patients with type 2 diabetes mellitus who have insufficient glycaemic control after 16 weeks of treatment with empagliflozin 10 mg or empagliflozin 25 mg once daily on a background of metformin;Secondary Objective: Fasting plasma glucose (FPG) change from baseline (Visit 5) at 24 weeks (or Visit 9);Primary end point(s): The primary endpoint is the change of HbA1c after 24 weeks of treatment (at week 24 or Visit 9) from baseline (Visit 5). ;Timepoint(s) of evaluation of this end point: After 24 weeks of treatment (Visit 9) from baseline (Visit 5).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Fasting plasma glucose (FPG) change from baseline (Visit 5) at 24 weeks (or Visit 9);Timepoint(s) of evaluation of this end point: After 24 weeks of treatment (Visit 9) from baseline (Visit 5).