4 Weeks Treatment With Empagliflozin (BI 10773) in Japanese Type 2 Diabetic Patients (T2DM)

Study Overview
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Brief Summary
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The objective of this trial is to evaluate the pharmacodynamics, pharmacokinetics, safety, and tolerability of once daily oral administration of BI 10773 administered for 28 days in Japanese patients with T2DM.

Official Title
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A Phase II, Randomised, Double-blind, Placebo-controlled, Multiple Dose Study to Evaluate Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Once Daily Oral Administration of BI 10773 (1 mg, 5 mg, 10 mg, and 25 mg) for 28 Days in Japanese Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo (middle dose)
* Drug: Placebo
* Drug: BI 10773
* Drug: BI 10773
* Drug: BI 10773
* Drug: Placebo (high dose)
* Drug: BI 10773
* Drug: Placebo (low dose)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Japanese male or female patients with T2DM treated with diet and exercise alone or with one hypoglycaemic drug other than glitazones. Hemoglobin A1c (HbA1c) at screening (Visit 1) For patients treated with 1 other oral antidiabetic drug: HbA1c between 6.5% and 9.0%. For patients not treated with any antidiabetic drug: HbA1c between 7.0% and 10.0%. Age between 20 and 70 years Body mass index (BMI) between18.0 and 40.0 kg/m2 Signed and dated written informed consent before admission to the trial in accordance with the Good Clinical Practice (GCP) and the local legislation. Exclusion criteria: Antidiabetic treatment with insulin or glitazones within 3 months before obtaining informed consent or with more than 1 oral hypoglycaemic agent at the time of informed consent Fasted blood glucose of >240 mg/dL (>13.3 mmol/L) or a randomly determined blood glucose level of >400 mg/dL (22.2 mmol/L) on 2 consecutive days during wash-out period. Myocardial infarction, stroke, or transient ischaemic attack within 6 months before informed consent. Clinically relevant concomitant diseases other than T2DM, hyperlipidaemia, and medically treated hypertension before the first administration such as Renal insufficiency (calculated estimated glomerular filtration rate <60) Cardiac insufficiency of New York Heart Association (NYHA) II-IV or other known cardiovascular diseases including hypertension of >160/95 mmHg, Neurological disorders (such as epilepsy) or psychiatric disorders Acute or clinically relevant chronic infections (e.g., human immunodeficiency virus, hepatitis, repeated urogenital infections) Any gastrointestinal, hepatic, respiratory, endocrine, or immunological disorder Patients under treatment with any concomitant medication except for the following drugs at the time of informed consent.: Statins. Antihypertensives (diuretics not allowed) alpha-Blockers for benign prostate hypertrophy Occasional use of acetylsalicylic acid, ibuprofen, or paracetamol Additional inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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 quaque die (QD)<br>patient to receive a BI 10773 low dose tablet and a placebo tablet once daily | Drug: BI 10773<br>* BI 10773 low dose tablets once a day<br>Drug: Placebo (low dose)<br>* Placebo tablets once a day<br>|
| Experimental: BI 10773 mid-low dose QD<br>patient to receive a BI 10773 middle dose tablet and a placebo tablet once daily | Drug: Placebo (middle dose)<br>* Placebo tablets once a day<br>Drug: BI 10773<br>* BI 10773 middle dose tablets once a day<br>|
| Experimental: BI 10773 mid-high dose QD<br>patient to receive two tablets of BI 10773 middle dose once daily | Drug: BI 10773<br>* BI 10773 middle dose tablets once a day<br>|
| Experimental: BI 10773 high dose QD<br>patient to receive a BI 10773 high dose tablet and a placebo tablet once daily | Drug: BI 10773<br>* BI 10773 high dose tablets once a day<br>Drug: Placebo (high dose)<br>* Placebo tablets once a day<br>|
| Placebo Comparator: Placebo<br>patient to receive two tablets of placebo once daily | Drug: Placebo<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 Urine Glucose Excretion | Change from baseline in Urine glucose excretion to 28 days | baseline and 28 days | 
| Change From Baseline in Fasting Plasma Glucose | Change from baseline in Fasting plasma glucose to 28 days | baseline and 28 days | 
| Change From Baseline in 8-point Glucose | Change from baseline in 8-point glucose to 27 days | baseline and 27 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c | Change from baseline in HbA1c to 28 days | baseline and 28 days | 
| Change From Baseline in Fructosamine | Change from baseline in Fructosamine to 28 days | baseline and 28 days | 
| Change From Baseline in 1,5-anhydroglucitol | Change from baseline in 1,5-anhydroglucitol to 28 days | baseline and 28 days | 
| Change From Baseline in Fasting Insulin | Change from baseline in Fasting insulin to 28 days | baseline and 28 days | 
| Change From Baseline in the Area Under the Curve of Plasma Glucose Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test) | Change from baseline in the area under the curve of plasma glucose levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days | baseline and 28 days | 
| Change From Baseline in the Area Under the Curve of Glucagon Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test) | Change from baseline in the area under the curve of glucagon levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days | baseline and 28 days | 
| Change From Baseline in the Area Under the Curve of Insulin Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test) | Change from baseline in the area under the curve of insulin levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days | baseline and 28 days | 
| AUCτ,1 | Area under the concentration-time curve of the analyte in plasma after administration of the first dose over a uniform dosing interval τ | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration | 
| AUC0-tz | area under the concentration-time curve of the analyte in plasma over the time interval from 0 to last quantifiable plasma concentration | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration | 
| AUC0-∞ | area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration | 
| Cmax | maximum measured concentration of the analyte in plasma | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration | 
| t1/2 | terminal half-life of the analyte in plasma | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration | 
| CL/F | apparent clearance of the analyte in plasma after extravascular administration | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration | 
| Vz/F | apparent volume of distribution during the terminal phase λz following an extravascular dose | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration | 
| Ae0-24 | amount of the analyte that is eliminated in urine over the time interval 0 to 24 | 0-5, 5-12, 12-24 hour after first drug administration | 
| fe0-24 | fraction of the analyte excreted unchanged in urine from time interval 0 to 24 | 0-5, 5-12, 12-24 hour after first drug administration | 
| CLR,0-24 | renal clearance of the analyte in plasma after extravascular administration - based on 0-24 hours data | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min, 0-5h, 5-12h, 12-24h after first drug administration | 
| AUCτ,ss | area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ at steady state | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration | 
| Cmax,ss | maximum measured concentration of the analyte in plasma at steady state | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration | 
| t1/2,ss | terminal half-life of the analyte in plasma at steady state | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration | 
| CL/F,ss | apparent clearance of the analyte in plasma after extravascular administration at steady state | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration | 
| Vz/F,ss | apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration | 
| RA,Cmax | accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on Cmax | Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration, and predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration | 
| RA,AUC | accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on AUCτ | Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration, and predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration | 
| Ae0-24,ss | amount of the analyte that is eliminated in urine at steady state over the time interval 0 to 24 | 0-5, 5-12, 12-24 hour after last drug administration | 
| fe0-24,ss | fraction of the analyte excreted unchanged in urine at steady state from time interval 0 to 24 | 0-5, 5-12, 12-24 hour after last drug administration | 
| CLR,ss | renal clearance of the analyte at steady state determined over the dosing interval τ | Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 0-5h, 5-12h, 12-24h after last drug administration |