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

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.

Study Overview

• Status: Completed
• Conditions: Renal Function Impairment in Healthy Volunteers
• Intervention / Treatment: Drug: Saline; Drug: VAS203

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • Universitätsklinik Erlangen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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)

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 -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Infusion (6 hours) of Saline	Drug: Saline; Infusion of saline; Other Names: 0.9% sodium chloride
ACTIVE_COMPARATOR: VAS203; Infusion (6 hours) of VAS203 (10 mg/kg)	Drug: VAS203; Infusion of NO-Synthase inhibitor VAS203; Other Names: Ronopterin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vasopharm GmbH
• Collaborators: Winicker Norimed GmbH
• Investigators: Principal Investigator: Roland E Schmieder, Prof. Dr., Universitätsklinik Erlangen

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (ACTUAL): May 1, 2016
• Study Completion (ACTUAL): November 1, 2016

Study Registration Dates

• First Submitted: December 7, 2016
• First Submitted That Met QC Criteria: December 9, 2016
• First Posted (ESTIMATE): December 14, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: VAS203/I/3/05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED