Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 113823 Powder in Bottle (PiB) and Tablet in Healthy Male Volunteers

Study Overview
=================
Brief Summary
-----------------
To investigate the safety, tolerability, and pharmacokinetics incl. dose proportionality of BI 113823, as well as the relative bioavailability of PiB vs. tablet and tablet fasted vs. fed (food effect for the tablet).

Official Title
-----------------
Investigation of Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of 5 to 800 mg BI 113823 Powder in Bottle (PiB) and Tablet Administered to Healthy Male Volunteers in a Partially Randomised and Double Blinded, Placebo Controlled Phase I Trial. Including Intra-individual Open Comparisons of PiB and Tablet (Fasted and Fed).

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: BI 113823 solution
* Drug: BI 113823 tablet
* Drug: Placebo
* Other: High fat, high calorie breakfast


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests Age ≥18 and Age ≤45 years BMI ≥18.5 and BMI ≤29.9 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: Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration 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 protocol preparation within 10 days prior to administration Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (more than 30 g/day) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration) Excessive physical activities (within one week prior to administration) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of trial site Bradycardia < 50/min, PR interval > 200 ms, QRS interval > 110 ms, QTcB > 450 ms, or QT (uncorrected) > 470 ms or any other relevant ECG findings at screening A history of additional risk factors for Torsades des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 113823 solution<br>single rising doses, dose group 5 twice (fed and fasted) | Drug: BI 113823 solution<br> <br> Other: High fat, high calorie breakfast<br>* only for dose group 5<br>|
| Experimental: BI 113823 tablet<br>dose group 5 only | Drug: BI 113823 tablet<br> <br> Other: High fat, high calorie breakfast<br>* only for dose group 5<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with clinically significant findings on physical examination |  | up to 14 days after last drug administration | 
| Number of participants with clinically significant findings in vital signs | blood pressure (BP), pulse rate (PR) | up to 14 days after last drug administration | 
| Number of participants with clinically significant findings in 12-lead electrocardiogram (ECG) | special attention to QRS prolongation | up to 14 days after last drug administration | 
| Number of participants with clinically significant findings in laboratory tests |  | up to 14 days after last drug administration | 
| Number of participants with adverse events |  | up to 14 days after last drug administration | 
| Assessment of tolerability by investigator on a 4-point scale |  | up to 14 days after last drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 72 hours after drug administration | 
| tmax (time from dosing to maximum measured concentration) |  | up to 72 hours after drug administration | 
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | up to 72 hours after drug administration | 
| AUC0-tz (area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | up to 72 hours after drug administration | 
| λz (terminal rate constant in plasma) |  | up to 72 hours after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 72 hours after drug administration | 
| MRToral (mean residence time of the analyte in the body after oral administration) |  | up to 72 hours after drug administration | 
| CL/F (total/apparent clearance of the analyte in plasma after extravascular administration) |  | up to 72 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | up to 72 hours after drug administration | 
| Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) |  | up to 72 hours after drug administration | 
| fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) |  | up to 72 hours after drug administration | 
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) |  | up to 72 hours after drug administration |