Clinical Study to see effect and safety of linagliptin 5mg compared to inactive drug,given as oral fixed dose combination with empagliflozin 10mg or 25mg for 24 wks,in pts with type 2 diabetes mellitus and uncontrolled glucose levels in bld after 16 wks of trtm with empa 10mg or 25mg & metformin.
- Conditions
- Health Condition 1: null- Type 2 Diabetes Mellitus
- Registration Number
- CTRI/2015/06/005914
- Lead Sponsor
- BoehringerIngelheim India Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Other (Terminated)
- Sex
- Not specified
- Target Recruitment
- 690
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)
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
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 observatio
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method change of HbA1cTimepoint: after 24 weeks of treatment (at week 24 or Visit 9) from baseline (Visit 5)
- Secondary Outcome Measures
Name Time Method Fasting plasma glucose (FPG) changeTimepoint: from baseline (Visit 5) at 24 weeks (or Visit 9)