Empagliflozin (BI 10773) Dose Finder Study in Japanese Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This study is conducted to determine the most appropriate therapeutic doses of BI 10773 in Japanese patients with T2DM at first treatment period. The second treatment period is required to obtain sufficient safety data (one-year exposure to BI 10773) in Japanese patients with T2DM according to the ICH E1 guideline.

Official Title
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A Double-blind, Randomised, Parallel Group Efficacy and Safety Study of BI 10773 (5 mg, 10 mg, 25 mg, and 50 mg) Compared to Placebo When Administered Orally Once Daily Over 12 Weeks, as Monotherapy, in Patients With Type 2 Diabetes and Insufficient Glycaemic Control Despite Diet and Exercise, Followed by a 40 Week Randomised Extension Study to Assess Long Term Safety of BI 10773 (10 mg and 25 mg)

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo (low dose)
* Drug: Placebo (low dose)
* Drug: Placebo (mid dose)
* Drug: Placebo (high dose)
* Drug: BI 10773
* Drug: Placebo (mid dose)
* Drug: Placebo (high dose)
* Drug: Placebo (high dose)
* Drug: BI 10773
* Drug: BI 10773
* Drug: Placebo (mid dose)
* Drug: Placebo (high dose)
* Drug: Placebo (low dose)
* Drug: Placebo (low dose)
* Drug: BI 10773
* Drug: Placebo (mid 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, defined as no antidiabetic drugs for 10 weeks prior to informed consent. pre-treated with one oral antidiabetic drug; the present antidiabetic therapy has to be unchanged for 10 weeks prior to informed consent. HbA1c at Visit 1a: for patients who are drug naïve: HbA1c >=7.0 to =<10.0% for patients treated with one oral antidiabetic drug: HbA1c >=6.5 to =<9.0% HbA1c of >=7.0% and =<10% at Visit 2 (start of run-in) Exclusion criteria: Uncontrolled hyperglycaemia with a glucose level >240 mg/dL (>13.3 mmol/L) after an overnight fast during wash-out/placebo run-in period and confirmed by a second measurement (not on the same day). Acute coronary syndromes, stroke or transient ischaemic attack within 12 weeks prior to informed consent Impaired renal function, defined as calculated eGFR <60 ml/min (MDRD formula) during screening and/or wash-out period and/or run-in phase. Bariatric surgery within the past 2 years and other gastrointestinal surgeries that induce chronic malabsorption Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia) Treatment with anti-obesity drugs (e.g. sibutramine, mazindol) 12 weeks 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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 QD<br>BI 10773 tablets low dose once a day | Drug: Placebo (mid dose)<br>* Placebo tablets once a day<br>Drug: Placebo (high dose)<br>* Placebo tablets once a day<br>Drug: BI 10773<br>* BI 10773 tablets low dose once a day<br>|
| Experimental: BI 10773 mid-low dose QD<br>BI 10773 tablets mid-low dose once a day | Drug: Placebo (high dose)<br>* Placebo tablets once a day<br>Drug: Placebo (low dose)<br>* Placebo tablets once a day<br>Drug: BI 10773<br>* BI 10773 tablets mid-low dose once a day<br>|
| Experimental: BI 10773 mid-high dose QD<br>BI 10773 tablets mid-high dose once a day | Drug: BI 10773<br>* BI 10773 tablets mid-high dose once a day<br>Drug: Placebo (high dose)<br>* Placebo tablets once a day<br>Drug: Placebo (low dose)<br>* Placebo tablets once a day<br>Drug: Placebo (mid dose)<br>* Placebo tablets once a day<br>|
| Experimental: BI 10773 high dose QD<br>BI 10773 tablets high dose once a day | Drug: Placebo (low dose)<br>* Placebo tablets once a day<br>Drug: Placebo (mid dose)<br>* Placebo tablets once a day<br>Drug: BI 10773<br>* BI 10773 tablets high dose once a day<br>|
| Placebo Comparator: Placebo<br>Placebo tablets once a day | Drug: Placebo (low dose)<br>* Placebo tablets once a day<br>Drug: Placebo (high dose)<br>* Placebo tablets once a day<br>Drug: Placebo (mid dose)<br>* Placebo tablets once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c After 12 Weeks of Treatment. | The primary endpoint in this study is the change from baseline in HbA1c after 12 weeks of treatment. | baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Treat to Target Efficacy Response | Occurrence of treat to target efficacy response, that is an HbA1c of <7.0% after 12 weeks of treatment | baseline and 12 weeks | 
| Change From Baseline in FPG | Change from baseline in FPG after 12 weeks of treatment | baseline and 12 weeks |