BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME).

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: BI 10773 low dose; Drug: Placebo BI 10773 low dose; Drug: Placebo BI 10773 high dose; Drug: BI 10773 high dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT01131676

2009-016178-33 (EudraCT Number)

1245.25

Details and patient eligibility

About

The aim of the present study is to investigate the safety of BI 10773 treatment in patients with Type 2 Diabetes Mellitus and high cardiovascular risk.

Enrollment: 7,064 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosis of type 2 diabetes mellitus prior to informed consent
2. Male or female patients on diet and exercise regimen who are drug naive or pre treated with any background therapy. Antidiabetic therapy has to be unchanged for 12 weeks prior to randomization.
3. Glycosylated haemoglobin (HbA1c) of >= 7.0% and <=10% for patients on background therapy or HbA1c >= 7.0% and <= 9.0% for drug naive patients
4. Age >= 18 years
5. Body Mass index <= 45 at Visit 1
6. Signed and dated informed consent
7. High cardiovascular risk

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. Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase ALT or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at screening and/or run in.

3. Planned cardiac surgery or angioplasty within 3 months

4. Impaired renal function, defined as Glomerular Filtration Rate <30 ml/min (severe renal impairment, Modification of Diet in Renal Disease formula) during screening or run in.

5. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption

6. Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia)

7. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years

8. Contraindications to background therapy according to the local label

9. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 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

10. 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 any other uncontrolled endocrine disorder except type 2 diabetes mellitus

11. 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, oral, implantable or injectable contraceptives, sexual abstinence, double barrier method and vasectomised partner

12. 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 study procedures or study drug intake

13. Participation in another trial with an investigational drug within 30 days prior to informed consent

14. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial

15. Acute coronary syndrome, stroke or TIA within 2 months prior to informed consent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

7,064 participants in 3 patient groups, including a placebo group

BI 10773 low dose

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo BI 10773 high dose

Drug: BI 10773 low dose

Drug: Placebo BI 10773 high dose

BI 10773 high dose

Experimental group

Description:

BI 10773 tablets once daily

Treatment:

Drug: Placebo BI 10773 low dose

Drug: BI 10773 high dose

Drug: Placebo BI 10773 low dose

Placebo

Placebo Comparator group

Description:

Placebo tablets matching BI 10773

Treatment:

Drug: Placebo BI 10773 low dose

Drug: Placebo BI 10773 high dose

Drug: Placebo BI 10773 low dose

Drug: Placebo BI 10773 high dose