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
- Diabetes mellitus type 2MedDRA version: 14.1Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2012-002271-34-IT
- Lead Sponsor
- BOEHRINGER ING.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1843
1.Diagnosis of type 2 diabetes mellitus prior to informed consent 2.Male and female patients on diet and exercise regimen and who are pre-treated with an unchanged dose of immediate release metformin for at least 12 weeks prior to Visit 2. Minimum dose for metformin is defined as: - >=1500 mg/day of metformin or - maximum tolerated dose (the investigator must have documented the reason why uptitration to e.g. >= 1500 mg/day was not possible) or - maximum dose according to the local label (the investigator must have documented the local label requirements in the medical records) Note: Medical records supporting metformin start date and dosage must be available. 3. HbA1c >= 8.0% (64 mmol/mol) and <= 10.5% (91 mmol/mol) at Visit 1 for randomization into the 16 week treatment period. 4. HbA1c >= 7.0% (53 mmol/mol) and <= 10.5 % (91 mmol/mol) at Visit 4 for randomization into the 24 week treatment period. 5. Age >= 18 years 6. Body Mass Index (BMI) <=45 kg/m2 at Visit 1 (screening) as calculated in the eCRF. 7. Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1383
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 460
1. 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) and confirmed by a second measurement (not on the same day and done either at the central or local laboratory). 2. Any other antidiabetic drug within 12 weeks prior to Visit 2 randomization (except metformin background therapy as defined via inclusion criterion 2). 3. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent 4. 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 and Visit 4 laboratory parameters. 5. 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) 6. Known hereditary galactose intolerance 7. Known contraindications to metformin or linagliptin according to the local label (where marketed) 8. Any previous (within the past two years) or planned bariatric surgery (or any other weight loss surgery) or other gastrointestinal surgery that induce chronic malabsorption 9. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years 10. 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. 11. 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 12. 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 13. Pre-menopausal women (last menstruation <=1 year prior to informed consent) who: - are nursing or pregnant or - 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, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, complete sexual abstinence (if acceptable by local health authorities), double barrier method and vasectomised partner 14. Known allergy or hypersensitivity to DPP4 inhibitors or SGLT-2 inhibitors 15. 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 trial procedures or trial drug intake, in the judgment of the investigator 16. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial 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 cl
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 linagliptin 5 mg qd compared to placebo given for 24 weeks in inadequately controlled T2DM patients on empagliflozin 10 mg or 25 mg and maximum tolerated dose of metformin. The study is designed to show superiority of the combination of empagliflozin and linagliptin over empagliflozin alone.;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).