Safety of Single Rising Doses and Relative Bioavailability of BI 691751

Study Overview
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Brief Summary
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To investigate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of single rising doses of BI 691751 in healthy male subjects (part I). To investigate the relative bioavailability of BI 691751 given as tablet versus oral solution (part II)

Official Title
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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising Oral Doses of BI 691751 in Healthy Male Volunteers in a Randomised, Single-blind, Placebo-controlled Design (Part I) and Investigation of Relative Bioavailability of BI 691751 Given as Tablet and Oral Solution to Healthy Male Subjects in an Open, Randomised, Single-dose, Single Period Parallel Group Design (Part II).

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 691751
* Drug: BI 691751
* Drug: Placebo
* Drug: BI 691751
* Drug: BI 691751
* Drug: BI 691751
* Drug: BI 691751
* Drug: BI 691751
* Drug: BI 691751
* Drug: BI 691751


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male subjects Subjects must be able to understand and comply with study requirements Age from 18 to 55 years BMI range: from 18.5 to 29.9 kg/m2 Known genotype as specified in the study protocol Exclusion criteria: 1. Any relevant deviation from healthy conditions

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 691751 dose 2 (part I)<br>single dose given as oral solution | Drug: BI 691751<br>* oral solution BI 691751, dose 2<br>|
| Experimental: BI 691751 dose 3 (part I)<br>single dose given as oral solution | Drug: BI 691751<br>* oral solution BI 691751, dose 3<br>|
| Experimental: BI 691751 dose 4 (part I)<br>single dose given as oral solution | Drug: BI 691751<br>* oral solution BI 69175, dose 4<br>|
| Experimental: BI 691751 dose 5 (part I)<br>single dose given as oral solution | Drug: BI 691751<br>* oral solution BI 691751, dose 5<br>|
| Experimental: BI 691751 dose 6 (part I)<br>single dose given as oral solution | Drug: BI 691751<br>* oral solution BI 691751, dose 6<br>|
| Experimental: BI 691751 dose 7 (part I)<br>single dose given as oral solution | Drug: BI 691751<br>* oral solution BI 691751, dose 7<br>|
| Experimental: BI 691751dose 1 (part I)<br>single dose given as oral solution | Drug: BI 691751<br>* oral solution BI 69175, dose 1<br>|
| Placebo Comparator: Placebo (part I)<br>placebo solution | Drug: Placebo<br>* placebo solution<br>|
| Experimental: BI 691751 tablet (part II)<br>single dose given as 1 tablet | Drug: BI 691751<br>* 1 tablet<br>|
| Active Comparator: BI 691751 solution (part II)<br>single dose given as oral solution | Drug: BI 691751<br>* oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-72h (Part II) | AUC0-72h (area under the concentration-time curve of the analyte of BI 691751 in plasma over the time interval from 0 to 72 h) (part II). PPS-BA included all subjects in the TS who were randomised to the BA part, who provided at least one observation for at least one primary endpoint, had no important protocol violations relevant for the statistical evaluation of BA and did not experience emesis at or before twice the median tmax. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h and 72h after drug administration | 
| Cmax (Part II) | Cmax (maximum measured concentration of the analyte of BI 691751 in plasma) (part II) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug administration | 
| Frequency of Subjects With Drug-related Adverse Events (Part I) | Frequency of subjects with drug-related Adverse Events (AEs) (Part I) | Part I: 'Day1 to Day21 for Dose 1, 2,3 &4 and Day1 to Day45 for Dose group 5,6 & 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (Part I) | Cmax (maximum measured concentration of BI 691751 in plasma) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | for dose 1 & 2: up to 168h, for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h | 
| AUC0-infinity (Part I) | AUC0-infinity (area under the concentration-time curve of BI 691751 in plasma over the time interval from 0 extrapolated to infinity) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h | 
| AUC0-tz | AUC0-tz (area under the concentration-time curve of BI 691751 in plasma over the time interval from 0 up to the last quantifiable data point) (Part I and Part II) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | Part 1: for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 7: up to 720h; Part 2: up to 720h | 
| t1/2 (Part I) | t1/2 (terminal half-life of the analyte of BI 691751 in plasma) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h | 
| Tmax (Part I) | tmax (time from dosing to maximum measured concentration of BI 691751) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |