Renal Function Impairment in Healthy Volunteers
Conditions
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.
Interventions
DRUGVAS203
Infusion of NO-Synthase inhibitor VAS203
DRUGSaline
Infusion of saline
Sponsors
Winicker Norimed GmbH
veriNOS operations GmbH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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 -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Serum Creatinine Concentration | 0, 2h, 4h, 6h, 8h, 10h, 24h and 48h after start of infusion |
Countries
Germany
Participant flow
Pre-assignment details
Cross-over design, all subjects received VAS203 and placebo
Participants by arm
| Arm | Count |
|---|---|
| Placebo, Then VAS203 Participants first received Placebo (6 hours Infusion of Saline). After a washout period of 4 weeks, they then received VAS203 (6 hours Infusion of 10 mg/kg VAS203). | 8 |
| VAS203, Then Placebo Participants first received VAS203 (6 hours Infusion of 10 mg/kg VAS203). After a washout period of 4 weeks, they then received Placebo (6 hours Infusion of Saline). | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | VAS203, Then Placebo | Placebo, Then VAS203 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 16 Participants |
| Age, Continuous | 31.2 years STANDARD_DEVIATION 7.9 | 31.2 years STANDARD_DEVIATION 7.9 | 31.2 years STANDARD_DEVIATION 7.9 |
| Region of Enrollment Germany | 8 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 1 / 16 | 5 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Glomerular Filtration Rate
by para-Amino-Hippuric Acid Clearance Method
Time frame: 0, 2h, 4h, 6h and 8 h after start of infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Glomerular Filtration Rate | 135 mL/min | Standard Deviation 15 |
| VAS203 | Glomerular Filtration Rate | 153.5 mL/min | Standard Deviation 15 |
Primary
Renal Plasma Flow
Renal plasma flow measurement by para-Amino-Hippuric-Acid Clearance Method
Time frame: 0, 2h, 4h, 6h and 8 h after start of infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Renal Plasma Flow | 541 mL/min | Standard Deviation 85 |
| VAS203 | Renal Plasma Flow | 663 mL/min | Standard Deviation 125 |
p-value: <0.0001Mixed Models Analysis
Secondary
Serum Creatinine Concentration
Time frame: 0, 2h, 4h, 6h, 8h, 10h, 24h and 48h after start of infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Serum Creatinine Concentration | 0.91 mg/dL | Standard Deviation 0.1 |
| VAS203 | Serum Creatinine Concentration | 0.94 mg/dL | Standard Deviation 0.1 |