Single Rising Dose Study to Assess Safety, Tolerability and Pharmacokinetics of BI 661051.

Study Overview
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Brief Summary
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The objective of the current study is to investigate safety, tolerability, and pharmacokinetics of treatment with BI 661051 rising single doses administered as oral drinking solution (powder in bottle) in healthy male subjects. The primary objective is to investigate the safety and tolerability of treatment with BI 661051. The secondary objectives are (1) to evaluate the single dose pharmacokinetics of BI 661051, (2) to explore dose proportionality, (3) to explore the relative bioavailability when BI 661051 is administered as tablet at two dose levels compared to oral drinking solution and (4) to assess the effect on the bioavailability when BI 661051 is administered as oral drinking solution after intake of a high fat meal. Pharmacodynamic parameters will not be determined within this study.

Detailed Description
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Purpose:

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 of 2 mg to 350 mg of BI 661051 Administered as Oral Drinking Solution (Powder in Bottle) in Healthy Male Volunteers, b) to Explore the Relative Oral Bioavailability of a 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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Healthy

Intervention / Treatment
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* Drug: BI 661051
* Drug: BI 661051
* Drug: BI 661051
* Drug: BI 661051
* Drug: BI 661051
* Drug: BI 661051
* Drug: BI 661051
* Drug: BI 661051
* Drug: BI 661051
* Drug: Placebo
* Drug: BI 661051


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy males based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), 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 =18 and age =50 years. BMI =18.5 and BMI =30 kg/m2 (Body Mass Index). Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (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. 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) as judged clinically relevant by the investigator. Intake of drugs with a long half-life (>24 h) within at least 1 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 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 30 days 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/day). Drug abuse. Blood donation (more than 100 mL 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: 18 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 661051 low dose, low<br>solution for oral administration, single dose | Drug: BI 661051<br>* low dose solution for oral administration<br>|
| Experimental: BI 661051 low dose, medium<br>solution for oral administration, single dose | Drug: BI 661051<br>* low dose solution for oral administration<br>|
| Experimental: BI 661051 low dose, high<br>solution for oral administration, single dose | Drug: BI 661051<br>* low dose solution for oral administration<br>|
| Experimental: BI 661051 medium dose, low<br>solution for oral administration, single dose | Drug: BI 661051<br>* medium dose solution for oral administration<br>|
| Experimental: BI 661051 medium dose, medium<br>solution for oral administration, single dose | Drug: BI 661051<br>* medium dose solution for oral administration<br>|
| Experimental: BI 661051 medium dose, high<br>solution for oral administration, single dose | Drug: BI 661051<br>* medium dose solution for oral administration<br>|
| Experimental: BI 661051 high dose, low<br>solution for oral administration, single dose | Drug: BI 661051<br>* high dose solution for oral administration<br>|
| Experimental: BI 661051 high dose, medium<br>solution for oral administration, single dose | Drug: BI 661051<br>* high dose solution for oral administration<br>|
| Experimental: BI 661051 low dose<br>tablet | Drug: BI 661051<br>* low dose tablet<br>|
| Experimental: BI 661051 medium dose<br>tablet | Drug: BI 661051<br>* medium dose tablet<br>|
| Placebo Comparator: Placebo<br>solution for oral administratrion | Drug: Placebo<br>* solution for administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of findings of physical examination |  | 14 weeks | 
| Vital signs (blood pressure (BP), pulse rate (PR), respiratory rate [RR]) |  | 14 weeks | 
| Orthostasis test parameters |  | 14 weeks | 
| Body temperature |  | 14 weeks | 
| 12-lead electrocardiogram (ECG) parameters (heart rate, PQ interval, QRS interval, uncorrected QT interval as well as Bazett- and Fridericia corrected QT interval) |  | 14 weeks | 
| Clinical laboratory test parameters (haematology, clinical chemistry and urinalysis parameters) |  | 14 weeks | 
| Occurrence of adverse events (AEs) on the level of Medical Dictionary for Regulatory Affairs (MedDRA) Preferred Terms and MedDRA System Organ Class |  | 14 weeks | 
| Occurrence of findings detected by the pupillometry measurements |  | 14 weeks | 
| Tolerability assessed by investigator |  | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | 14 weeks | 
| AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | 14 weeks | 
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable analyte plasma concentration) |  | 14 weeks | 
| Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) |  | 14 weeks |