Safety and efficacy of empagliflozin in two different daily doses as add-on to metformin therapy in patients with type 2 diabetes mellitus

Conditions: Type 2 diabetes mellitus
MedDRA version: 14.1Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 100000004861
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2012-000905-53-LV

Lead Sponsor: Boehringer Ingelheim RCV GmbH & Co KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 936

Inclusion Criteria

1. Diagnosis of type 2 diabetes mellitus prior to informed consent.
2. Male and female patients on diet and exercise regimen currently
treated with metformin (IR) alone.
A total daily dose of =1500 mg/day metformin divided into twice daily administration (e.g., 850 mg bid, 1000 mg bid, 850/1000 mg bid or 500/1000 mg bid) is required for inclusion into the trial. A patient taking metformin tid can be included if switched to a biddosing regimen at the time of informed consent. In this case, the total daily dose must be maintained (e.g., 500 mg tid to 1000/500 mg bid, 1000/500/500 mg tid to 1000 bid, 500/500/850 mg tid to 1000/850 mg bid).
3. The total daily dosage of metformin needs to be stable for at least 12 weeks prior to randomisation and is expected to be stable throughout the duration of the study.
4. HbA1c = 7.0% and = 10% (=53.0 mmol/mol and =85.8 mmol/mol) at Visit 1 (screening)
5. Age =18 at Visit 1 (screening)
6. BMI =45 kg/m2 (Body Mass Index) at Visit 1 (screening).
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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 702
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 234

Exclusion Criteria

1. Uncontrolled hyperglycaemia with a glucose level >240 mg/dl
(>13.3 mmol/L) after an overnight fast during placebo run-in and
confirmed by a second measurement (not on the same day).
2. Any other antidiabetic medication within 12 weeks prior to
randomisation, except the one defined as the permitted background therapy via inclusion criterion no. 2
3. Treatment with extended release formulations of metformin within12 weeks prior to consent
4. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischaemic attack (TIA) within 3 months prior to informed consent.
5. 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) as determined during screening and/or run-in period
6. Impaired renal function, defined as estimated creatinine clearance rate (eCCr) <60 ml/min (Cockcroft-Gault formula) as determined during screening and/or run-in period
7. Bariatric surgery within the past two years and other
gastrointestinal surgeries that induce chronic malabsorption
8. Known medical history of cancer (except for basal cell carcinoma)
and/or treatment for cancer within the last 5 years
9. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cell (e.g. malaria, babesiosis, haemolytic anaemia)
10. Contraindications to metformin according to the local label (e.g.
SPC)
11. Treatment with anti-obesity drugs 3 months prior to informed
consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) which, in the opinion of Investigator, may lead to unstable body weight
12. Current treatment with systemic steroids at time of informed
consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or other 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 study 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, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner
14. Alcohol or drug abuse within the 3 months prior to informed
consent that, in the opinion of Investigator, would interfere with trial participation or any ongoing condition leading to a decreased
compliance to study procedures or study drug intake.
15. Intake of an investigational drug in another trial within 30 days
prior to intake of study medication in this trial
16. Any other clinical condition that, in the opinion of the Investigator, would jeopardize patient's safety while participating in this clinical trial

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the efficacy and safety of different dosage regimens of empagliflozin, 5mg twice daily compared to 10 mg once daily versus placebo and 12.5 mg twice daily compared to 25 mg once daily versus placebo, administered orally as add-on therapy to metformin in patients with T2DM and insufficient glycaemic control;Secondary Objective: None;Primary end point(s): The primary endpoint in this study is the change from baseline in<br>HbA1c after 16 weeks of treatment;Timepoint(s) of evaluation of this end point: 16 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1.Fasting plasma glucose (FPG)<br>Change from baseline after 16 weeks of treatment<br>Change from baseline by visit over time<br>2. HbA1c: Change from baseline in HbA1c by visit over time;Timepoint(s) of evaluation of this end point: 16 weeks

Related Trials