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

Phase 1

Completed

• Conditions: Renal Function Impairment in Healthy Volunteers
• Interventions: Drug: Saline; Drug: VAS203

• Registration Number: NCT02992236
• Lead Sponsor: veriNOS operations GmbH

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-08
• Primary Completion: 2016-05
• Study Completion: 2016-11
• Study First Submitted: 2016-12-07
• Study First Submitted QC: 2016-12-09
• Study First Posted: 2016-12-14
• Results First Submitted: 2019-03-21
• Status Verified: 2019-08
• Results First Submitted QC: 2019-08-08
• Last Update Submitted: 2019-08-08
• Results First Posted: 2019-08-09
• Last Update Posted: 2019-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 16

Inclusion Criteria

1. Informed consent in writing available.
2. Willing and able to comply with all requirements of the study.
3. Male, 18 and 45 years (inclusive).
4. Subject has a body weight between 60 kg and 100 kg, extremes included.
5. BMI 18 to 27 kg/m2.
6. Non-smoker
7. Serum creatinine within reference range (≤1.2 mg/dL) and Cockroft-Gault Clearance > 90 ml/min
8. 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)

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Exclusion Criteria

1. Clinically significant abnormalities in physical examination, vital signs or clinical laboratory parameters (according to the Investigator's judgment).
2. Serum glutamate oxaloacetate transaminase or glutamate-pyruvate transaminase > 2-times above the upper limit of normal range.
3. Subject with Cockcroft-Gault clearance < 90 ml/min.
4. Clinically significant history of cardiovascular disease or any known present cardiovascular disease.
5. History of clinically significant neurological, gastrointestinal, renal, hepatic, psychological, pulmonary, metabolic, endocrine, hematological, or other major disorders.
6. Office blood pressure at screening higher than 160/100 mmHg, or lower than 95/55 mmHg.
7. Office heart rate at screening after at least 5 minutes outside the range of 50- 99 beats per minute (inclusive).
8. Concomitant use of OTC medication within 1 week prior to dosing, except use of paracetamol (up to 2 g/day).
9. Participation in any other clinical study within 30 days prior to inclusion in this -

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Saline	Infusion (6 hours) of Saline
VAS203	VAS203	Infusion (6 hours) of VAS203 (10 mg/kg)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Serum Creatinine Concentration	0, 2h, 4h, 6h, 8h, 10h, 24h and 48h after start of infusion

Trial Locations

Locations (1)

Universitätsklinik Erlangen; 🇩🇪 Erlangen, Germany