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

Primary Purpose

Diabetes Mellitus, Type 2

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

BI 10773 low dose

Placebo BI 10773 high dose

BI 10773 high dose

Placebo BI 10773 low dose

Placebo BI 10773 high dose

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Diagnosis of type 2 diabetes mellitus prior to informed consent
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.
Glycosylated haemoglobin (HbA1c) of >= 7.0% and <=10% for patients on background therapy or HbA1c >= 7.0% and <= 9.0% for drug naive patients
Age >= 18 years
Body Mass index <= 45 at Visit 1
Signed and dated informed consent
High cardiovascular risk

Exclusion criteria:

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)
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.
Planned cardiac surgery or angioplasty within 3 months
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.
Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia)
Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
Contraindications to background therapy according to the local label
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
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
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
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
Participation in another trial with an investigational drug within 30 days prior to informed consent
Any other clinical condition that would jeopardize patients safety while participating in this clinical trial
Acute coronary syndrome, stroke or TIA within 2 months prior to informed consent

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

BI 10773 low dose

BI 10773 high dose

Placebo

Arm Description

BI 10773 tablets once daily

Placebo tablets matching BI 10773

Outcomes

Primary Outcome Measures

Time to the First Occurrence of Any of the Following Adjudicated Components of the Primary Composite Endpoint (3-point MACE): CV Death (Including Fatal Stroke and Fatal MI), Non-fatal MI (Excluding Silent MI), and Non-fatal Stroke.

Time to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point major adverse cardiovascular events (MACE)): cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI (excluding silent MI), and non-fatal stroke. Percentage of patients with the event are presented.

Secondary Outcome Measures

Percentage of Participants With the Composite of All Events Adjudicated (4-point MACE): CV Death (Including Fatal Stroke and Fatal MI), Non-fatal MI (Excluding Silent MI), Non-fatal Stroke and Hospitalization for Unstable Angina Pectoris

The composite of all events adjudicated (4-point MACE): cardiovascular death (including fatal stroke and fatal myocardial infarction), non-fatal myocardial infarction (excluding silent MI), non-fatal stroke and hospitalization for unstable angina pectoris.This is a key secondary endpoint of the trial. Percentage of patients with the event are presented.

Percentage of Participants With Silent MI

Silent MI; defined as presence in the ECG of: Any Q-wave in leads V2-V3 ≥0.02 seconds or QS complex in leads V2 and V3 Q-wave ≥0.03 seconds and ≥0.1 mV deep or QS complex in leads I, II, aVL, aVF, or V4-V6 in any two leads of a contiguous lead grouping (I, aVL, V6; V4-V6; II, III, and aVF) R-wave ≥0.04 seconds in V1-V2 and R/S ≥1 with a concordant positive T-wave in the absence of a conduction defect. It was also required that there had been no adjudicated and confirmed event of either acute MI, hospitalisation for unstable angina, coronary revascularisation procedures or stent thrombosis following randomisation up to and including the date of the specified ECG measurement. Percentage of patients with the event are presented.

Percentage of Participants With Heart Failure Requiring Hospitalisation (Adjudicated)

Heart failure requiring hospitalisation (adjudicated). Percentage of patients with the event are presented.

Percentage of Participants With New Onset Albuminuria

New onset albuminuria defined as urine albumin / creatinine ratio (UACR) ≥30 mg/g. Percentage of patients with the event are presented.

Percentage of Participants With New Onset Macroalbuminuria

New onset macroalbuminuria defined as UACR >300 mg/g. Percentage of patients with the event are presented.

Percentage of Participants With the Composite Microvascular Outcome

Composite microvascular outcome defined as: Initiation of retinal photocoagulation Vitreous haemorrhage Diabetes-related blindness, or New or worsening nephropathy defined as: New onset of macroalbuminuria; or Doubling of serum creatinine level accompanied by an eGFR (based on modification of diet in renal disease (MDRD) formula) ≤45 mL/min/1.73m2; or Initiation of continuous renal replacement therapy, or Death due to renal disease. Percentage of patients with the event are presented.

Full Information

NCT ID

NCT01131676

First Posted

May 26, 2010

Last Updated

April 7, 2016

Sponsor

Boehringer Ingelheim

Collaborators

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01131676

Brief Title

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

Official Title

A Phase III, Multicentre, International, Randomised, Parallel Group, Double Blind Cardiovascular Safety Study of BI 10773 (10 mg and 25 mg Administered Orally Once Daily) Compared to Usual Care in Type 2 Diabetes Mellitus Patients With Increased Cardiovascular Risk

Study Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Completed

Study Start Date

July 2010 (undefined)

Primary Completion Date

April 2015 (Actual)

Study Completion Date

April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

Collaborators

Eli Lilly and Company

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Double

Allocation

Randomized

Enrollment

7064 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BI 10773 low dose

Arm Type

Experimental

Arm Description

BI 10773 tablets once daily

Arm Title

BI 10773 high dose

Arm Type

Experimental

Arm Description

BI 10773 tablets once daily

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo tablets matching BI 10773

Intervention Type

Drug

Intervention Name(s)

BI 10773 low dose

Intervention Description

BI 10773 tablets once daily

Intervention Type

Drug

Intervention Name(s)

Placebo BI 10773 high dose

Intervention Description

Placebo tablets identical to BI 10773

Intervention Type

Drug

Intervention Name(s)

BI 10773 high dose

Intervention Description

BI 10773 tablets once daily

Intervention Type

Drug

Intervention Name(s)

Placebo BI 10773 low dose

Intervention Description

Placebo tablets identical to BI 10773

Intervention Type

Drug

Intervention Name(s)

Placebo BI 10773 low dose

Intervention Description

Placebo tablets identical to BI 10773

Intervention Type

Drug

Intervention Name(s)

Placebo BI 10773 high dose

Intervention Description

Placebo tablets identical to BI 10773

Primary Outcome Measure Information:

Title

Description

Time Frame