To Investigate Safety, Tolerability, and Pharmacokinetics of Treatment With BI 660848 Rising Single Doses (From 2 mg to 600 mg) Administered as Oral Drinking Solution (Powder in Bottle).

Study Overview
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Brief Summary
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As a transition from preclinical investigations to clinical development in this first-in-human trial, safety, tolerability, and pharmacokinetics of BI 660848 will be assessed in human male volunteers using single rising oral doses in order to provide the basis for a potential ongoing clinical development of BI 660848 in the indication of neuropathic pain.

Official Title
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A Randomised, Double-blind, Placebo-controlled (Within Dose Groups) Phase I - Study to a) Assess Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses 2 mg to 600 mg of BI 660848 Administered as Oral Drinking Solution (Powder in Bottle) in Healthy Male Volunteers, b) to Explore the Relative Oral Bioavailability of an Immediate Release Tablet Formulation and c) to Assess the Impact of a High Fat Meal on the Oral Bioavailability of the Oral Drinking Solution (Powder in Bottle).

Conditions
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Pain, Healthy

Intervention / Treatment
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* Drug: BI 660848
* Drug: BI 660848
* Drug: BI 660848
* Drug: BI 660848
* Drug: BI 660848
* Drug: BI 660848
* Drug: BI 660848
* Drug: BI 660848
* Drug: BI 660848
* Drug: BI 660848
* Drug: BI 660848
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Healthy male based upon a complete medical history, including the physical examination, regarding vital signs (BP, PR), 12 lead ECG measurement, and clinical laboratory tests. There is no finding deviating from normal and of clinical relevance. There is no evidence of a clinically relevant concomitant disease. Age 21 and 50 years BMI 18.5 and <30 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 measurements) deviating from normal and of clinical relevance Evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 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 the drug or its excipients) as judged clinically relevant by the investigator Intake of drugs with a long half-life (24 hours) within at least 1 month or less than 10 half-lives of the respective drug prior to randomisation Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to randomisation Participation in another trial with an investigational drug within 2 months prior to randomisation Smoker (>10 cigarettes or >3 cigars or >3 pipes/day) Inability to refrain from smoking on trial days as judged by the investigator Alcohol abuse (more than 30 g alcohol a day) Drug abuse Blood donation (more than 100 mL blood within 4 weeks prior to randomisation or during the trial) Excessive physical activities within 1 week prior to randomisation or during the trial Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of the study centre

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 660848 2 mg<br>oral drinking solution | Drug: BI 660848<br>* 2 mg oral drinking solution<br>|
| Experimental: BI 660848 10 mg<br>oral drinking solution | Drug: BI 660848<br>* 10 mg oral drinking solution<br>|
| Experimental: BI 660848 20 mg<br>oral drinking solution | Drug: BI 660848<br>* 20 mg oral drinking solution<br>|
| Experimental: BI 660848 50 mg<br>oral drinking solution | Drug: BI 660848<br>* 50 mg oral drinking solution<br>|
| Experimental: BI 660848 100 mg<br>oral drinking solution | Drug: BI 660848<br>* 100 mg oral drinking solution<br>|
| Experimental: BI 660848 150 mg<br>oral drinking solution | Drug: BI 660848<br>* 150 mg oral drinking solution<br>|
| Experimental: BI 660848 200 mg<br>oral drinking solution | Drug: BI 660848<br>* 200 mg oral drinking solution<br>|
| Experimental: BI 660848 400 mg<br>oral drinking solution | Drug: BI 660848<br>* 400 mg oral drinking solution<br>|
| Experimental: BI 660848 600 mg<br>oral drinking solution | Drug: BI 660848<br>* 600 mg oral drinking solution<br>|
| Experimental: BI 660848 10,0 mg<br>immediate release tablet | Drug: BI 660848<br>* 10,0 mg immediate release tablet<br>|
| Experimental: BI 660848 50,0 mg<br>immediate release tablet | Drug: BI 660848<br>* 50,0 mg immediate release tablet<br>|
| Experimental: Placebo<br>matching placebo (oral drinking solution and IR tablets) | Drug: Placebo<br>* matching placebo (oral drinking solution and IR tablets)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability (number and intensity of adverse events). |  | 4 months | 
| Changes in blood pressure. |  | 4 months | 
| Changes in pulse rate. |  | 4 months | 
| Changes in respiratory rate. |  | 4 months | 
| Changes in 12-lead ECG. |  | 4 months | 
| Changes in clinical laboratory test parameters. |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | 3 days | 
| tmax (time from dosing to maximum measured concentration) |  | 3 days | 
| AUC (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | 3 days | 
| t1/2 (terminal half-life of the analyte in plasma) |  | 3 days | 
| MRT (mean residence time of the analyte in the body after drug intake) |  | 3 days | 
| CL/F (apparent clearance of the analyte in plasma after extravascular administration) |  | 3 days | 
| Vz/F (apparent volume of distribution during the terminal phase following an extravascular dose) |  | 3 days | 
| Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) |  | 3 days | 
| fet1-t2 (fraction of analyte eliminated in urine from the time point t1 to time point t2) |  | 3 days | 
| CL R,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) |  | 3 days |