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

• ClinicalTrials.gov Identifier: NCT02992236
• Recruitment Status: Completed
• First Posted: December 14, 2016
• Results First Posted: August 9, 2019
• Last Update Posted: August 9, 2019
• Sponsor: Vasopharm GmbH
• Collaborator: Winicker Norimed GmbH
• Information provided by (Responsible Party): Vasopharm GmbH

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Renal Function Impairment in Healthy Volunteers	Drug: VAS203; Drug: Saline	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Effects of the NO-synthase Inhibitor VAS203 on Renal Function in Healthy Volunteers
• Study Start Date: August 2015
• Actual Primary Completion Date: May 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Infusion (6 hours) of Saline	Drug: Saline; Infusion of saline; Other Name: 0.9% sodium chloride
Active Comparator: VAS203; Infusion (6 hours) of VAS203 (10 mg/kg)	Drug: VAS203; Infusion of NO-Synthase inhibitor VAS203; Other Name: Ronopterin

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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 -

Contacts and Locations

Locations

Germany

Universitätsklinik Erlangen

Erlangen, Germany, 91054

Sponsors and Collaborators

Vasopharm GmbH

Winicker Norimed GmbH

Investigators

• Principal Investigator: Roland E Schmieder, Prof. Dr.; Universitätsklinik Erlangen

More Information

• Responsible Party: Vasopharm GmbH
• ClinicalTrials.gov Identifier: NCT02992236
• Other Study ID Numbers: VAS203/I/3/05
• First Posted: December 14, 2016
• Results First Posted: August 9, 2019
• Last Update Posted: August 9, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided