4 Weeks Treatment of Type II Diabetic Patients With BI 44847

Study Overview
=================
Brief Summary
-----------------
The primary objective of the current study is to investigate the safety and tolerability of BI 44847 in male and female patients with type 2 diabetes following oral administration of repeated doses of 100 mg b.i.d, 400 mg b.i.d. and 800 mg b.i.d. over 28 days. A secondary objective is the exploration of the pharmacokinetics and pharmacodynamics of BI 44847 after multiple dosing, including assessment of steady state.

Official Title
-----------------
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 4 Weeks Treatment With Three Selected Oral Doses of BI 44847 as Tablet in Female and Male Patients With Type 2 Diabetes.

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: BI 44847
* Drug: placebo for BI 44847


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and postmenopausal or hysterectomised female patients with proven diagnosis of type 2 diabetes mellitus treated with diet and exercise only or with one or 2 oral hypoglycaemic agent other than glitazones. In case of 2 oral hypoglycaemic agents, at least one of these may be taken at no more than 50% of its maximum dose; Age = > 21 and Age = <70 years (female hysterectomised and male patients); Age = >55 and Age = <70 years (female postmenopausal patients); BMI = >18.5 and BMI = <40 kg/m2 (Body Mass Index); Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation. Exclusion Criteria: Treatment with insulin, glitazones, or more than one oral hypoglycaemic agent (except if 2 agents and at least one of them not taken at more than 50% of maximum dose); Fasted blood glucose > 240 mg/dl on two consecutive days during wash-out; HbA1c > 8.5 % at screening; Clinically relevant concomitant diseases other than type 2 diabetes, hyperlipidaemia and medically treated hypertension; History of relevant allergy/hypersensitivity; Marked baseline prolongation of QT/QTc interval; History of additional risk factors for TdP; Any laboratory value outside the reference range and the clinical relevance is not acceptable in the opinion of the investigator, or the value is more than 3 times higher than the upper limit of the reference range; Concomitant medication except for acetylsalicylic acid, statins, antihypertensives (diuretics not allowed), beta-blockers for BPH and occasional use of paracetamol (doses of no more than 1000 mg; no more than 2000 mg per day; no more than 2 days per week); Change of drug dosing of allowed co-medication < the last 6 weeks; Intake of any medication < 5 half-lives of the respective drug prior to first administration of study medication or during the trial, except allowed co-medication; Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval (based on the knowledge at the time of patient inclusion) < 10 days prior to first administration of study medication or during the trial; Use of grapefruit (or its juice) < 10 days prior to first administration of study medication or during the trial; Participation in another trial with an investigational drug < two months prior to first administration of study medication or during the trial; Smoker; Inability to refrain from smoking on specified trial days; Alcohol abuse; Drug abuse; Blood donation; Excessive physical activity; Male patients not using adequate contraception; Women of childbearing potential, positive pregnancy test or lactating

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: BI 44847|nan|
|Drug: placebo for BI 44847|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight and waist circumference - change from baseline |  | Day 28 (Hour = 647:30) | 
| Frequency of patients with maximal increase from baseline QTcF and QTcB interval |  | 4 weeks | 
| Frequency of patients with possible clinically significant abnormalities |  | 4 weeks | 
| Micturition total frequency - change from baseline |  | Day 28 | 
| Global tolerability - number of patients by category |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum concentration of the analyte in plasma) |  | Day 1 | 
| Tmax (time from dosing to maximum concentration) |  | Day 1 | 
| t1/2 (terminal half-life of the analyte in plasma) |  | Day 1 | 
| λz (terminal rate constant in plasma) |  | Day 1 | 
| C12,1 (concentration of analyte in plasma at 12 hours post-drug administration after administration of the first dose) |  | Day 1 | 
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point within the first dosing interval) |  | Day 1 | 
| AUC0-12 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 h after administration of the first dose) |  | Day 1 | 
| Ae0-12 (amount of analyte that is eliminated in urine over the time interval 0 h to 12 h) |  | Day 1 | 
| fe0-12 (fraction of analyte excreted unchanged in urine from time points 0 h to 12 h) |  | Day 1 | 
| CLR (renal clearance of the analyte in plasma after extravascular administration - based on 0 - 12 hour data) |  | Day 1 | 
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) |  | Day 1 | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | Day 1 | 
| Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval) |  | Day 28 | 
| Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval) |  | Day 28 | 
| Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N) |  | Day 28 | 
| Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the last dose) |  | Day 28 | 
| C12,ss (concentration of analyte in plasma at 12 hours post-drug administration at steady state) |  | Day 28 | 
| tmax,ss (time from dosing to maximum concentration at steady state) |  | Day 28 | 
| tmin,ss (time from dosing to minimum concentration during a dosing interval) |  | Day 28 | 
| AUC0-tz,ss (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point within the last dosing interval) |  | Day 28 | 
| AUC0-12,ss (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 h at steady-state) |  | Day 28 | 
| MRTpo,ss (mean residence time of the analyte in the body after 56 administrations (b.i.d.) at steady state) |  | Day 28 | 
| CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) |  | Day 28 | 
| Vz/F,ss (apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state) |  | Day 28 | 
| Ae0-12,ss (amount of analyte that is eliminated in urine at steady state over the time interval 0 to 12 h) |  | Day 28 | 
| fe0-12,ss (fraction of analyte excreted unchanged in urine at steady state over the time interval 0 to 12 h) |  | Day 28 | 
| CLR,ss (renal clearance of the analyte at steady state - based on 0 - 12 hour data) |  | Day 28 | 
| RA,Cmax based on Cmax |  | following 55 doses (bid) | 
| RA,AUC based on AUCτ |  | following 55 doses (bid) | 
| Predose concentrations of the analyte in plasma |  | 5 minutes before drug administration on days 2,3,4,7,14,21,26,27,28 and 29 | 
| Change from baseline in UGE, AE0-24 |  | Day 27 | 
| Change from baseline in weighted MDG, AUEC0-24 |  | Day 27 | 
| Epre-corrected AUEC0-5 following OGTT |  | Day 28 | 
| Cavg (average concentration) |  | day 28 | 
| PTF (peak trough fluctuation). |  | day 28 |