Effects of the NO-synthase Inhibitor VAS203 on Renal Function in Healthy Volunteers

Study Overview
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Brief Summary
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Analysis of the effect of the NO-Synthase inhibitor VAS203 (6 hours infusion of 10 mg/kg) on renal function and perfusion in 16 healthy subjects.

Detailed Description
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Analysis of the effect of i.v. VAS203 on renal function and perfusion in healthy subjects. Primary objective: Possible adverse effect of VAS203 on the Renal Plasma Flow (RPF) and the Glomerular Filtration Rate (GFR) during and after 6 hours of constant-rate iv. infusion of 10 mg/kg VAS203. Secondary objective: To analyse the effects of VAS203 on filtration fraction hemodynamics (afferent and efferent resistance, intraglomerular pressure) markers of kidney injury and renal function systolic, mean and diastolic brachial blood pressure Plasma Pharmacokinetic of VAS203 and its first metabolite.

Official Title
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Effects of the NO-synthase Inhibitor VAS203 on Renal Function in Healthy Volunteers

Conditions
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Renal Function Impairment in Healthy Volunteers

Intervention / Treatment
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* Drug: VAS203
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent in writing available. Willing and able to comply with all requirements of the study. Male, 18 and 45 years (inclusive). Subject has a body weight between 60 kg and 100 kg, extremes included. BMI 18 to 27 kg/m2. Non-smoker Serum creatinine within reference range (≤1.2 mg/dL) and Cockroft-Gault Clearance > 90 ml/min Good general health as judged by the Investigator, as determined by medical history, physical examination, vital signs (systolic and diastolic blood pressure and pulse rate) and clinical laboratory parameters (clinical chemistry, hematology, and urinalysis) Exclusion Criteria: Clinically significant abnormalities in physical examination, vital signs or clinical laboratory parameters (according to the Investigator's judgment). Serum glutamate oxaloacetate transaminase or glutamate-pyruvate transaminase > 2-times above the upper limit of normal range. Subject with Cockcroft-Gault clearance < 90 ml/min. Clinically significant history of cardiovascular disease or any known present cardiovascular disease. History of clinically significant neurological, gastrointestinal, renal, hepatic, psychological, pulmonary, metabolic, endocrine, hematological, or other major disorders. Office blood pressure at screening higher than 160/100 mmHg, or lower than 95/55 mmHg. Office heart rate at screening after at least 5 minutes outside the range of 50- 99 beats per minute (inclusive). Concomitant use of OTC medication within 1 week prior to dosing, except use of paracetamol (up to 2 g/day). Participation in any other clinical study within 30 days prior to inclusion in this -

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Infusion (6 hours) of Saline | Drug: Saline<br>* Infusion of saline<br>* Other names: 0.9% sodium chloride;|
| Active Comparator: VAS203<br>Infusion (6 hours) of VAS203 (10 mg/kg) | Drug: VAS203<br>* Infusion of NO-Synthase inhibitor VAS203<br>* Other names: Ronopterin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Plasma Flow | Renal plasma flow measurement by para-Amino-Hippuric-Acid Clearance Method | 0, 2h, 4h, 6h and 8 h after start of infusion | 
| Glomerular Filtration Rate | by para-Amino-Hippuric Acid Clearance Method | 0, 2h, 4h, 6h and 8 h after start of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Creatinine Concentration |  | 0, 2h, 4h, 6h, 8h, 10h, 24h and 48h after start of infusion |