Trial to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Oral Doses of BI135585 XX Administered as Tablet and as Solution in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of the study is to investigate the safety, tolerability, pharmacokinetics incl. dose proportionality, and pharmacodynamics of BI 135585 XX (Part 1), as well as the relative bioavailability of two different immediate release tablet formulations versus oral solution (Part 2)

Official Title
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A Randomised, Double-blind, Placebo-controlled Trial to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of 10 mg to 1200 mg of BI 135585 XX Administered as a Solution to Healthy Male Volunteers (Trial Part 1), Followed by an Open, Randomised, Single-dose, Intra-individual Bioavailability Comparison of 200 mg BI 135585 XX as Tablet and as Solution (Trial Part 2)

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo to BI 135585
* Drug: BI 135585


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: - healthy male volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 135585<br>1 single dose per subject as oral solution in Part 1, or 3 single doses per subject as oral solution and 2 different tablet formulations in Part 2 | Drug: BI 135585<br>* Part 1 - oral doses given to approximately 9 parallel groups of 8 subjects (6 on active and 2 on placebo) on Day 1; Part 2 - oral doses given to 12 subjects on Day 1<br>|
| Placebo Comparator: Placebo to BI 135585<br>1 single dose per subject as oral solution in Part 1 | Drug: Placebo to BI 135585<br>* Part 1 - oral doses given to approximately 9 parallel groups of 8 subjects (6 on active and 2 on on placebo) on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Physical examination (occurrence of findings) |  | up to 14 days post treatment | 
| Change from baseline in Vital signs (blood pressure [BP], pulse rate [PR], respiratory rate [RR]) |  | up to 14 days post treatment | 
| Change from baseline in 12-lead ECG with special attention to QTc prolongation |  | up to 14 days post treatment | 
| Cardiopulmonary monitoring resulting in clinically relevant findings |  | up to 14 days post treatment | 
| Change from baseline in Clinical laboratory parameters including hormones of the HPA axis and thyroid gland |  | up to 14 days post treatment | 
| Number of patients with Adverse events (AE) |  | up to 14 days post treatment | 
| Assessment of tolerability by the investigator |  | up to 14 days post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 post treatment | 
| (5α-THF + 5β-THF)/THE ratio as an indicator of 11β-HSD1 inhibition |  | up to 24h | 
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | up to 72 hours post treatment | 
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 72 hours post treatment | 
| tmax (time from dosing to maximum measured concentration) |  | up to 72 hours post treatment | 
| %AUCtz-∞ (percentage of the AUC0-∞ that was obtained by extrapolation) |  | up to 72 hours post treatment | 
| λz (terminal rate constant in plasma) |  | up to 72 hours post treatment | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 72 hours post treatment | 
| MRToral (mean residence time of the analyte in the body after oral administration) |  | up to 72 hours post treatment | 
| CL/F (total/apparent clearance of the analyte in plasma after extravascular administration) |  | up to 72 hours post treatment | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | up to 72 hours post treatment | 
| Aet1-t2 (amount of analyte eliminated in urine from timepoint t1 to timepoint t2) SRD part only |  | up to 72 hours post treatment | 
| fet1-t2 (fraction of analyte eliminated in urine from timepoint t1 to timepoint t2) SRD part only |  | up to 72 hours post treatment | 
| CLR,t1-t2 (renal clearance of the analyte from timepoint t1 to timepoint t2) SRD part only[ |  | up to 72 hours post treatment | 
| UFF/UFE ratio as an indicator of 11β-HSD2 inhibition |  | up to 24h | 
| Total urinary corticosteroids (5α-THF + 5β-THF + THE + UFF + UFE) as an indicator of the activation of the HPA axis |  | up to 24h |