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

NCT07502144 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: 23-VIN-0367CTRI/2026/02/104919
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

VRP-034; Polymyxin B; PMB; supramolecular cationic formulation; nephrotoxicity; kidney injury biomarkers; novel urinary kidney injury biomarkers; polymyxin b-associated kidney injury; Acute kidney injury; Renal Guard Programme; NAG; NGAL; KIM-1; Cystatin C; Osteopontin; Clusterin; ELISA

Outcome Measures

Primary Outcomes (1)

• 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)

  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 Outcomes (10)

• 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)

  24 hours after first dose (multiple-dose cohort); 48 hours after dosing (SAD cohorts 2 and 3)

• Maximum plasma concentration (Cmax) of polymyxin B

  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

  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

  Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14

• Change from baseline in serum creatinine

  Baseline (pre-dose), Day 1, Day 2, Day 7, Day 14

Study Arms (4)

Cohort 1

EXPERIMENTAL

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); Drug: Commercially available Polymyxin B 500,000 IU (Poly-MxB)

Cohort 2

EXPERIMENTAL

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); Drug: Commercially available Polymyxin B 500,000 IU (Poly-MxB)

Cohort 3

EXPERIMENTAL

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); Drug: Commercially available Polymyxin B 500,000 IU (Poly-MxB)

Cohort 4

EXPERIMENTAL

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); Drug: Commercially available Polymyxin B 500,000 IU (Poly-MxB)

Interventions

VRP-034 (Polymyxin B 500,000 IU) DRUG

VRP-034 (Novel formulation of polymyxin B 500,000 IU) of Venus Remedies Limited

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Commercially available Polymyxin B 500,000 IU (Poly-MxB) DRUG

Commercially available Polymyxin B 500,000 IU (Poly-MxB)

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Venus Remedies Limited: lead

Study Sites (1)

Veeda Clinical Research Ltd

Ahmedabad, Gujarat, 380015, India

Location

Related Publications (3)

• Vishwakarma K, Bisht A, Kumar P, Kumar S, Akhter J, Payasi A, Chaudhary S, Aggarwal A. Toxicokinetic profiling of VRP-034: Evaluating its potential in mitigating polymyxin-B-associated nephrotoxicity. Int J Antimicrob Agents. 2025 Feb;65(2):107393. doi: 10.1016/j.ijantimicag.2024.107393. Epub 2024 Nov 28.

  PMID: 39612992 BACKGROUND

• Payasi A, Yadav MK, Chaudhary S, Aggarwal A. Evaluating nephrotoxicity reduction in a novel polymyxin B formulation: insights from a 3D kidney-on-a-chip model. Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0021924. doi: 10.1128/aac.00219-24. Epub 2024 Sep 3.

  PMID: 39225483 BACKGROUND

• Pye K, Tasinato E, Shuttleworth S, Devlin C, Brown C. Comparison of the Impact of VRP-034 and Polymyxin B upon Markers of Kidney Injury in Human Proximal Tubule Monolayers In Vitro. Antibiotics (Basel). 2024 Jun 6;13(6):530. doi: 10.3390/antibiotics13060530.

  PMID: 38927196 BACKGROUND

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Polymyxin B

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins

Study Officials

• Hiren Prajapati, MD Pharmacology

  Veeda Clinical Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sumit Saxena

CONTACT

91-9875910291; pv_hod@venusremedies.com

Anmol Aggarwal

CONTACT

anmolaggarwal@venusremedies.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: March 30, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)