Single Rising Dose (SRD), Multiple Rising Dose (MRD) Study of BI 671800 in Healthy Asian Volunteers

Study Overview
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Brief Summary
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The primary objective of the current study is to investigate the safety and tolerability of BI 671800 HEA in healthy Chinese male volunteers following single oral administration, and healthy Japanese male volunteers following single oral administration and multiple administrations.

Official Title
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A Randomised, Double-blind (Within Dose Groups), Parallel Group, Placebocontrolled Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Rising Doses (50 mg, 200 mg, 400 mg) of BI 671800 HEA in Chinese Healthy Male Volunteers and Multiple Rising Doses (50 mg b.i.d., 200 mg b.i.d., 400 mg b.i.d.) of BI 671800 HEA in Japanese Healthy Male Volunteers

Conditions
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Asthma, Rhinitis, Allergic, Perennial

Intervention / Treatment
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* Drug: BI 671800
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy Chinese ethnicity for single rising dose (SRD) part, Japanese Ethnicity for multiple rising dose (MRD) part. Age >= 20 and age =< 50 Body Mass Index (BMI) >=18.5 and BMI =< 25 kg/m2 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 blood pressure (BP), pulse rate (PR) and electrocardiogram (ECG)) deviating from normal and of clinical relevance according to the investigators medical judgement Any evidence of a clinically relevant concomitant disease Intake of drugs with long half life (>24 hour) within at least one month or less than 10 half-lives of the respective drug prior to administration

Ages Eligible for Study
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Minimum Age: 20 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 671800 active<br>SRD part: 3 dose groups each consisting of 12 subjects (9 active, 3 placebo), subjects receive single dose. MRD part: 3 dose groups each consisting of 12 subjects (9 active, 3 placebo), subjects receive single dose followed by multiple doses with a PK sampling interval in between. | Drug: BI 671800<br>* In the SRD part subjects will receive a single dose and in the MRD part subjects will receive a total of 14 doses.<br>|
| Placebo Comparator: Placebo<br>3 subjects will receive placebo in each of the 3 doses in the SRD part and 3 doses in the MRD part | Drug: placebo<br>* Subjects will receive according to the dose group matching number of placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical examination |  | up to 4 days for SRD part and up to 15 days for MRD part | 
| Vital signs; Blood Pressure(BP) |  | up to 4 days for SRD part and up to 15 days for MRD part | 
| Vital signs; Pulse rate(PR) |  | up to 4 days for SRD part and up to 15 days for MRD part | 
| 12-lead Electrocardiogram (ECG) |  | up to 4 days for SRD part and up to 15 days for MRD part | 
| Clinical laboratory tests (Hematology) |  | up to 4 days for SRD part and up to 15 days for MRD part | 
| Clinical laboratory tests (Clinical chemistry) |  | up to 4 days for SRD part and up to 15 days for MRD part | 
| Clinical laboratory tests (Urinalysis) |  | up to 4 days for SRD part and up to 15 days for MRD part | 
| Adverse events |  | up to 4 days for SRD part and up to 15 days for MRD part | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SRD Part, Cmax (maximum measured concentration of the analyte in plasma) BI 671800 and BI 600957 |  | up to 4 days | 
| SRD Part, tmax (time from dosing to maximum measured concentration), BI 671800 and BI 600957 |  | up to 4 days | 
| SRD Part, AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time point t1 to time point t2), BI 671800 and BI 600957 |  | up to 4 days | 
| SRD Part, AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable concentration at tz) BI 671800 and BI 600957 |  | up to 4 days | 
| SRD Part, AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity), BI 671800 and BI 600957 |  | up to 4 days | 
| SRD Part, %AUCtz-infinity (the percentage of the AUC 0-infinity that is obtained by extrapolation), BI 671800 and BI 600957 |  | up to 4 days | 
| SRD Part, λz (terminal rate constant in plasma) ), BI 671800 and BI 600957 |  | up to 4 days | 
| SRD Part, t1/2 (terminal half-life of the analyte in plasma) BI 671800 and BI 600957 |  | up to 4 days | 
| SRD Part, MRTpo (mean residence time of the analyte in the body after oral administration) BI 671800 and BI 600957 |  | up to 4 days | 
| SRD Part, CL/F (apparent clearance of the analyte in plasma after oral administration); only BI671800 |  | up to 4 days | 
| SRD Part, Vz/F (apparent volume of distribution during the terminal phase λ z following an oral dose); only BI 671800 |  | up to 4 days | 
| MRD Part , Cmax (maximum measured concentration of the analyte in plasma) BI 671800 and BI 600957 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, tmax (time from dosing to maximum measured concentration), BI 671800 and BI 600957 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time point t1 to time point t2), BI 671800 and BI 600957 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable concentration at tz), BI 671800 and BI 600957 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) , BI 671800 and BI 600957 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, %AUCtz-infinity (the percentage of the AUC 0-infinity that is obtained by extrapolation), BI 671800 and BI 600957 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, λz (terminal rate constant in plasma) ), BI 671800 and BI 600957 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, t1/2 (terminal half-life of the analyte in plasma) BI 671800 and BI 600957 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, MRTpo (mean residence time of the analyte in the body after oral administration) BI 671800 and BI 600957 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, CL/F (apparent clearance of the analyte in plasma after oral administration); only BI671800 |  | day1 Visit2, day1 Visit3 | 
| MRD Part, Vz/F (apparent volume of distribution during the terminal phase λz following an oral dose); only BI 671800 |  | day1 Visit2, day1 Visit 3 | 
| MRD Part, Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ, BI 671800 and BI 600957 |  | up to 12 days | 
| MRD Part, tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state) BI 671800 and BI 600957 |  | up to 12 days | 
| MRD Part, Cmin,ss (minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ) BI 671800 and BI 600957 |  | up to 12 days | 
| MRD Part,tmin,ss (time from last dosing to minimum concentration of the analyte in plasma at steady state) BI 671800 and BI 600957 |  | up to 12 days | 
| MRD Part,Cpre,ss (predose concentration of the analyte in plasma immediately before administration of dose at steady state) BI 671800 and BI 600957 |  | up to 12 days | 
| MRD Part,AUCt1-t2,ss (area under the concentration-time curve of the analyte in plasma at steady state over the time interval t1 to t2) BI 671800 and BI 600957 |  | up to 12 days | 
| MRD Part,AUC τ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) BI 671800 and BI 600957 |  | up to 12 days | 
| MRD Part,λz ,ss (terminal rate constant in plasma at steady state) BI 671800 and BI 600957 |  | up to 12 days | 
| MRD Part,t1/2,ss (terminal half-life of the analyte in plasma at steady state) BI 671800 and BI 600957 |  | up to 12 days | 
| MRTpo,ss (mean residence time of the analyte in the body at steady state after xx administration) BI 671800 and BI 600957 |  | up to 12 days | 
| CL/F,ss (apparent clearance of the analyte in the plasma at steady state following extravascular multiple dose administration); only BI 671800 |  | up to 12 days | 
| Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration); only BI 671800 |  | up to 12 days | 
| Accumulation ratios RA,Cmax, 13 based on Cmax after the first dose and at steady state |  | up to 12 days | 
| Accumulation ratios RA,AUC,13 based on AUC τ after the first dose and at steady state |  | up to 12 days | 
| Linearity index (LI) of the analyte in plasma |  | up to 12 days | 
| AUEC0-24,N absolute inhibition of eosinophil shape change: area under the absolute inhibition of shape change-time curve after the Nth dose of BI 671800 HEA |  | up to day 9 | 
| AUEC0-24,N percent inhibition of eosinophil shape change: area under the percent inhibition of shape change - time curve after the Nth dose of BI 671800 |  | up to day 9 |