Efficacy and Safety of Empagliflozin (BI 10773) Versus Placebo and Sitagliptin Over 24 Weeks in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The aim of this study is to investigate the efficacy, safety and tolerability of BI 10773 compared to placebo and sitagliptin given for 24 weeks as monotherapy in patients with T2DM with insufficient glycaemic control. For the open-label part of the study the objective is to estimate the efficacy and safety of BI 10773 when given for 24 weeks in patients with T2DM with very poor glycaemic control.

Official Title
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A Phase III Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 10773 and Sitagliptin Administered Orally Over 24 Weeks, in Drug naïve Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control Despite Diet and Exercise

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo identical to BI10773 high dose
* Drug: BI 10773
* Drug: BI 10773 open label
* Drug: Placebo identical to BI10773 low dose
* Drug: Placebo identical to BI10773 low dose
* Drug: Placebo identical to BI10773 high dose
* Drug: Placebo identical to Sitagliptin 100mg
* Drug: Placebo identical to Sitagliptin 100mg
* Drug: BI10773
* Drug: Sitagliptin
* Drug: Placebo identical to Sitagliptin 100mg
* Drug: Placebo identical to BI10773 low dose
* Drug: Placebo identical to BI10773 high dose


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of type 2 diabetes mellitus prior to informed consent; Male and female patients on diet and exercise regimen who are drug-naïve; HbA1c >= 7.0% and <= 10.0% at Visit 1 (screening) for randomised treatment; HbA1c > 10.0% at visit 1 (screening) for the open-label BI 10773 arm; Age >= 20 (Japan); Age >= 18 (countries other than Japan); BMI <= 45 kg/m2 at Visit 1 (screening); Signed and dated written informed consent by date of Visit 1 Exclusion criteria: Uncontrolled hyperglycaemia; Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent; Indication of liver disease, either ALT, AST, or alkaline phosphatase above 3 x ULN; Impaired renal function (eGFR<50 ml/min); Bariatric surgery within the past two years or other GI surgeries; Medical history of cancer; Contraindications to sitagliptin; Blood dyscrasias or any disorders causing haemolysis or unstable red blood cell; Treatment with any anti-diabetes drug within 12 weeks prior to randomisation; Treatment with anti-obesity drugs or any other treatment leading to unstable body weight; Current treatment with systemic steroids or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM; Pre-menopausal women who are nursing or pregnant or are of child-bearing potential and not practicing an acceptable method of birth control; Alcohol or drug abuse; Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial; Any other clinical condition that would jeopardize patients safety while participating in this clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 10773 low dose<br>Patients receive BI 10773 low dose tablets once daily | Drug: Placebo identical to BI10773 high dose<br>* placebo tablets once daily<br>Drug: BI 10773<br>* BI 10773 low dose tablet once daily<br>Drug: Placebo identical to Sitagliptin 100mg<br>* placebo tablets once daily<br>|
| Experimental: BI 10773 high dose<br>Patients receive BI 10773 high dose tablets once daily | Drug: Placebo identical to BI10773 low dose<br>* placebo tablets once daily<br>Drug: BI10773<br>* BI 10773 high dose tablets once daily<br>Drug: Placebo identical to Sitagliptin 100mg<br>* placebo tablets once daily<br>|
| Placebo Comparator: Placebo<br>Patients receive tablets identical to those containing BI 10773 low dose and high dose and to Sitagliptin | Drug: Placebo identical to BI10773 low dose<br>* placebo tablets once daily<br>Drug: Placebo identical to Sitagliptin 100mg<br>* placebo tablets once daily<br>Drug: Placebo identical to BI10773 high dose<br>* placebo tablets once daily<br>|
| Active Comparator: Sitagliptin 100 mg<br>Patients receive Sitagliptin 100 mg tablets once daily | Drug: Placebo identical to BI10773 high dose<br>* placebo tablets once daily<br>Drug: Sitagliptin<br>* Sitagliptin tablets 100 mg once daily<br>Drug: Placebo identical to BI10773 low dose<br>* placebo tablets once daily<br>|
| Experimental: BI 10773 high dose open label<br>Patients receive BI 10773 high dose tablets open label once daily | Drug: BI 10773 open label<br>* Patients receive BI 10773 high dose tablets open label once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) After 24 Weeks | The term baseline refers to the last observation before the start of randomised trial treatment (or of open-label treatment for the open-label arm). In this endpoint, the measured values show unadjusted values, whereas the statistical analyses show adjusted values. Statistics for open-label group are descriptive. | Baseline and day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 24 in Body Weight | The term baseline refers to the last observation before the start of randomised trial treatment (or of open-label treatment for the open-label arm). In this endpoint, the measured values show unadjusted values, whereas the statistical analyses show adjusted values. Statistics for open-label group are descriptive. | Baseline and day 169 | 
| Change From Baseline to Week 24 in Systolic and Diastolic Blood Pressure (SBP and DBP) | The term baseline refers to the last observation before the start of randomised trial treatment (or of open-label treatment for the open-label arm). In this endpoint, the measured values show unadjusted values, whereas the statistical analyses show adjusted values. Statistics for open-label group are descriptive. For blood pressure, data following changes in antihypertensive therapy is censored, in the same way that data following initiation of rescue medication is censored. | Baseline and week 24 |