Effect of Repeated Doses of BI 1060469 and BI 1021958 on Glomerular Filtration Rate (GFR) in Healthy Volunteers

Study Overview
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Brief Summary
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Main objective is to investigate the measured glomerular filtration rate (mGFR) as assessed by iohexol clearance in healthy male normovolemic subjects after oral administration of single and repeated doses of BI 1060469, and BI 1021958. The secondary objective of this trial is to investigate the glomerular filtration rate (GFR) as assessed by 24 hours creatinine clearance in healthy male normovolemic subjects after oral administration of single and repeated doses of BI 1060469, and BI 1021958.

Official Title
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Effect of Repeated Oral Doses of BI 1060469, BI 1021958 and Active Controls, Cimetidine and Naproxen, on Measured GFR Via Renal Clearance of Iohexol in Healthy Male Subjects (a Phase I Study; Single-blind, Randomized, Placebo-controlled Within BI Groups and Open-label for the Active Controls)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Placebo
* Drug: Cimetidine
* Drug: Placebo
* Drug: Placebo
* Drug: BI 1060469 high dose
* Drug: BI 1060469 low dose
* Drug: Naproxen
* Drug: BI 1021958


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male subjects according to the investigators assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests, including negative test result on occult blood in stool (only for subjects assigned to Naproxen) Age 18 to 45 years (incl.) Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.) Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice (GCP) and local legislation Exclusion criteria: Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged clinically relevant by the investigator Repeated measurement of systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, or pulse rate outside the range of 50 to 90 mmHg Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Serum creatinine laboratory value out of the normal range GFR (Glomerular Filtration Rate) < 90 mL/ min at screening Urinary toral protein/creatinine ratio > 0,1 mg protein/ mg creatinine Current or history of relevant kidney, urinary tract diseases or abnormalities (i.e. nephrolithiasis, hydronephrosis, acute or chronic nephritis, renal injury, renal failure, infections) Further exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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 1060469 low dose<br>Low-Dose,Tablet,oral administration with 240 ml water,over 10 days | Drug: Placebo<br>* tablets<br>Drug: BI 1060469 low dose<br>* tablets<br>|
| Experimental: BI 1060469 high dose<br>High-Dose,Tablets,oral administration with 240 ml water, over 10 days | Drug: Placebo<br>* tablets<br>Drug: BI 1060469 high dose<br>* tablets<br>|
| Active Comparator: Cimetidine<br> | Drug: Cimetidine<br> <br> |
| Active Comparator: Naproxen<br> | Drug: Naproxen<br> <br> |
| Experimental: BI 1021958<br>High-Dose,Tablets,oral administration with 240 ml water, over 10 days | Drug: Placebo<br>* tablets<br>Drug: BI 1021958<br>* tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| measured glomerular filtration rate (mGFR) based on renal iohexol clearance |  | up to day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| measured urinary 24-hour creatinine clearance |  | up to day 11 |