Clinical trial NCT02992236: Effects of the NO-synthase Inhibitor VAS203 on Renal Function in Healthy Volunteers
Official title: Effects of the NO-synthase Inhibitor VAS203 on Renal Function in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Function Impairment in Healthy Volunteers
Lead sponsor: veriNOS operations GmbH
Sponsor class: INDUSTRY
Collaborators: name: Winicker Norimed GmbH
First posted: 2016-12-14
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Eligibility criteria: 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 -

Primary outcomes:
measure: Renal Plasma Flow
timeFrame: 0, 2h, 4h, 6h and 8 h after start of infusion
measure: Glomerular Filtration Rate
timeFrame: 0, 2h, 4h, 6h and 8 h after start of infusion
Secondary outcomes:
measure: Serum Creatinine Concentration
timeFrame: 0, 2h, 4h, 6h, 8h, 10h, 24h and 48h after start of infusion
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Universitätsklinik Erlangen
Study officials:
affiliation: Universitätsklinik Erlangen
name: Roland E Schmieder, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: