A Phase I Study Comparing the Safety, Pharmacokinetics and Renal Effects of VRP-034 and Marketed Polymyxin B in Healthy Volunteers (VRP-034)

March 24, 2026 updated by: Venus Remedies Limited

A Single Center, Prospective, Double-blind, Balanced, Randomized, Two-treatment, Single-period, Single Ascending Dose (SAD) and Multiple-dose, Parallel, Phase I, Study to Compare the Safety, Tolerability and Pharmacokinetics of Test Formulation VRP-034 (Novel Formulation of Polymyxin B 500,000 IU) of Venus Remedies Limited vs Commercially Available Polymyxin B for Injection USP (Poly-MxB) 500,000 IU in Normal Healthy Adult Male Human Subjects

This is a Phase 1, single-center, randomized, double-blind, active-controlled clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and nephrotoxicity attenuation potential of VRP-034 compared with commercially available polymyxin B in healthy adult male volunteers.

VRP-034 is a supramolecular cationic formulation of polymyxin B developed with the objective of mitigating polymyxin B-associated nephrotoxicity while preserving its established antibacterial activity against MDR Gram-negative pathogens. Although polymyxin B remains an important last-line therapy for serious infections caused by carbapenem-resistant organisms, its clinical use is limited by dose-dependent renal toxicity.

VRP-034 has been developed with a strategy aimed at reducing kidney injury without compromising antimicrobial exposure, and preclinical studies have demonstrated an improved renal safety profile compared with conventional formulations.

This study consists of three single ascending dose (SAD) cohorts followed by one multiple-dose cohort. In the SAD phase, subjects will receive weight-based intravenous doses of polymyxin B (0.4 mg/kg, 0.75 mg/kg, and 1.5 mg/kg) administered over specified infusion durations. The multiple-dose cohort will receive 1.5 mg/kg every 12 hours for up to 2 days. An independent Data Safety Monitoring Board (DSMB) will review safety and pharmacokinetic data after each SAD cohort prior to dose escalation and before initiation of the multiple-dose cohort. The primary objective is to assess the effect of VRP-034 on polymyxin B-associated nephrotoxicity using a composite measure of novel urinary kidney injury biomarkers (qualified by US FDA). Secondary objectives include assessment of safety, tolerability, and pharmacokinetic parameters.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Healthy adult male human subjects aged between 18 and 45 years, both inclusive.
  • Subjects weight within normal range according to normal values for Body Mass Index 18.50 to 28.00 kg/m2, both inclusive with minimum of 50 kg weight.
  • Subjects with normal health as determined by personal medical history, clinical examination and laboratory examinations within the clinically acceptable range.
  • Subject with creatinine Clearance greater than and equal to 90 ml per min.
  • Subjects with haemoglobin greater than and equal to 11.5 gm percentage at the time of screening.
  • Subject should be non smoker, non alcoholic. Further details as mentioned in the approved protocol

Exclusion Criteria:

  • Have significant diseases or clinically significant abnormal findings during screening like medical history, physical examination, laboratory evaluations, ECG, and chest X ray.
  • History or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, urogenital or psychiatric disease or disorder.
  • Use of any hormone replacement therapy within three months prior to admission.
  • A depot injection or implant of any drug within three months prior to admission
  • Subjects with G6PD deficiency.
  • Abnormal USG KUB or clinically significant findings in volunteers
  • Difficulty with donating blood.
  • Positive screening test for any one or more i.e HIV, Hepatitis B and Hepatitis C or syphilis RPR.
  • Any other issue which, in the judgment of the Investigator, will make the subject ineligible for study participation Further details as mentioned in the approved protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
VRP-034 (Novel formulation of Polymyxin B 500,000 IU) of Venus Remedies Limited and Poly-MxB (Marketed Polymyxin B 500,000 IU) dose of 0.4 mg per kg in first SAD Cohort, total 6 subjects (3 subjects to receive either VRP-034 or Poly-MxB), 1.5 hours IV infusion.
Drug: VRP-034 (Polymyxin B 500,000 IU)
VRP-034 (Novel formulation of polymyxin B 500,000 IU) of Venus Remedies Limited
Drug: Commercially available Polymyxin B 500,000 IU (Poly-MxB)
Commercially available Polymyxin B 500,000 IU (Poly-MxB)
Experimental: Cohort 2
VRP-034 (Novel formulation of Polymyxin B 500,000 IU) of Venus Remedies Limited and Poly-MxB (Marketed Polymyxin B 500,000 IU) dose of 0.75 mg per kg in first SAD Cohort, total 6 subjects (3 subjects to receive either VRP-034 or Poly-MxB), 1.5 hours IV infusion.
Drug: VRP-034 (Polymyxin B 500,000 IU)
VRP-034 (Novel formulation of polymyxin B 500,000 IU) of Venus Remedies Limited
Drug: Commercially available Polymyxin B 500,000 IU (Poly-MxB)
Commercially available Polymyxin B 500,000 IU (Poly-MxB)
Experimental: Cohort 3
VRP-034 (Novel formulation of Polymyxin B 500,000 IU) of Venus Remedies Limited and Poly-MxB (Marketed Polymyxin B 500,000 IU) dose of 1.5 mg per kg in first SAD Cohort, total 6 subjects (3 subjects to receive either VRP-034 or Poly-MxB), 3 hours IV infusion.
Drug: VRP-034 (Polymyxin B 500,000 IU)
VRP-034 (Novel formulation of polymyxin B 500,000 IU) of Venus Remedies Limited
Drug: Commercially available Polymyxin B 500,000 IU (Poly-MxB)
Commercially available Polymyxin B 500,000 IU (Poly-MxB)
Experimental: Cohort 4
VRP-034 (Novel formulation of Polymyxin B 500,000 IU) of Venus Remedies Limited and Poly-MxB (Marketed Polymyxin B 500,000 IU) doses of 1.5 mg per kg in fourth Multidose Cohort (12 hourly two days dosing, total four doses), total 18-30 subjects (9 -15 subjects to receive either VRP-034 or Poly-MxB), 3 hours IV infusion.
Drug: VRP-034 (Polymyxin B 500,000 IU)
VRP-034 (Novel formulation of polymyxin B 500,000 IU) of Venus Remedies Limited
Drug: Commercially available Polymyxin B 500,000 IU (Poly-MxB)
Commercially available Polymyxin B 500,000 IU (Poly-MxB)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Geometric Mean of Fold Changes From Baseline in Six Urinary Kidney Injury Biomarkers (CLU, CysC, KIM-1, NAG, NGAL, OPN), Each Normalized to Urine Creatinine (Composite Measure)
Time Frame: 48 hours after first dose (multiple-dose cohort); 24 hours after dosing (SAD cohorts 2 and 3)

The composite measure (CM) is calculated for each subject as the geometric mean of fold changes from baseline in six urinary biomarkers: Clusterin (CLU), Cystatin-C (CysC), Kidney Injury Molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), Neutrophil Gelatinase-Associated Lipocalin (NGAL), and Osteopontin (OPN). Each biomarker is normalized to urine creatinine prior to analysis. Fold change is defined as the ratio of post-dose to pre-dose normalized values. The CM is calculated as the exponential of the arithmetic mean of natural log-transformed fold changes. A CM value of 1.0 indicates no change from baseline, while higher values indicate increased nephrotoxicity and lower values indicate reduced nephrotoxicity.

The natural log-transformed CM (ln[CM]) will be compared between treatment groups using an analysis of variance (ANOVA) model.
48 hours after first dose (multiple-dose cohort); 24 hours after dosing (SAD cohorts 2 and 3)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Geometric Mean of Fold Changes From Baseline in Six Urinary Kidney Injury Biomarkers (CLU, CysC, KIM-1, NAG, NGAL, OPN), Each Normalized to Urine Creatinine (Composite Measure)
Time Frame: 24 hours after first dose (multiple-dose cohort); 48 hours after dosing (SAD cohorts 2 and 3)

The composite measure (CM) is calculated for each subject as the geometric mean of fold changes from baseline in six urinary biomarkers: Clusterin (CLU), Cystatin-C (CysC), Kidney Injury Molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), Neutrophil Gelatinase-Associated Lipocalin (NGAL), and Osteopontin (OPN). Each biomarker is normalized to urine creatinine prior to analysis. Fold change is defined as the ratio of post-dose to pre-dose normalized values. The CM is calculated as the exponential of the arithmetic mean of natural log-transformed fold changes. A CM value of 1.0 indicates no change from baseline, while higher values indicate increased nephrotoxicity and lower values indicate reduced nephrotoxicity.

The natural log-transformed CM (ln[CM]) will be compared between treatment groups using an analysis of variance (ANOVA) model.
24 hours after first dose (multiple-dose cohort); 48 hours after dosing (SAD cohorts 2 and 3)
Maximum plasma concentration (Cmax) of polymyxin B
Time Frame: SAD cohorts: up to 48 hours post-dose; multiple-dose cohort: up to 12 hrs after first dose and up to 48 hrs after fourth dose.
Cmax will be derived from plasma concentration-time data using non-compartmental analysis and summarized by treatment group.
SAD cohorts: up to 48 hours post-dose; multiple-dose cohort: up to 12 hrs after first dose and up to 48 hrs after fourth dose.
Area under the plasma concentration-time curve (AUC0-t) of polymyxin B
Time Frame: SAD cohorts: up to 48 hours post-dose; multiple-dose cohort: up to 12 hours post first dose and up 48 hrs post fourth dose
AUC0-t will be calculated using non-compartmental methods, and summarized by treatment group.
SAD cohorts: up to 48 hours post-dose; multiple-dose cohort: up to 12 hours post first dose and up 48 hrs post fourth dose
Number of participants with acute kidney injury (AKI) based on RIFLE criteria
Time Frame: Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
AKI will be assessed using serum creatinine changes from baseline and classified according to RIFLE criteria (Risk, Injury, Failure). Incidence will be summarized by treatment group.
Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Change from baseline in serum creatinine
Time Frame: Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Serum creatinine values will be measured and summarized as change from baseline by treatment group and time point.
Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Change from baseline in blood urea nitrogen (BUN)
Time Frame: Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
BUN values will be measured and summarized as change from baseline by treatment group and time point.
Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Change from baseline in urinary creatinine
Time Frame: Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Urinary creatinine levels will be measured and summarized as change from baseline by treatment group and time point.
Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Change from baseline in urinary albumin
Time Frame: Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Urinary albumin levels will be measured and summarized as change from baseline by treatment group and time point.
Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Change from baseline in urine total protein
Time Frame: Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Urine total protein will be measured and summarized as change from baseline by treatment group and time point.
Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14
Number of participants with treatment-emergent adverse events (TEAEs)
Time Frame: From first dose up to Day 14
Treatment-emergent adverse events (TEAEs) are defined as any adverse event occurring or worsening after administration of study drug. TEAEs will be summarized by treatment group, severity (CTCAE v5.0), and relationship to study drug.
From first dose up to Day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Venus Remedies Limited

Investigators

  • Principal Investigator: Hiren Prajapati, MD Pharmacology, Veeda Clinical Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

March 9, 2026

First Submitted That Met QC Criteria

March 24, 2026

First Posted (Actual)

March 30, 2026

Study Record Updates

Last Update Posted (Actual)

March 30, 2026

Last Update Submitted That Met QC Criteria

March 24, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-VIN-0367
  • CTRI/2026/02/104919 (Registry Identifier: Clinical Trials Registry - India)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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