Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT07502144

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

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Healthy Volunteers Acute Kidney Injury Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Renal Insufficiency Urogenital Diseases Urologic Diseases

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Veeda Clinical Research Ltd

Ahmedabad, Gujarat, 380015, India

Location contact

Hiren Prajapati, MD (Pharmacology)

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

VRP-034 (Polymyxin B 500,000 IU)

Drug

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

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

Drug

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

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)

    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.

Secondary 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)

    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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Anmol Aggarwal

CONTACT

[email protected]

Sumit Saxena

CONTACT

[email protected]

91-9875910291

Sponsors and collaborators

Lead sponsor

Venus Remedies Limited

Industry

Registry information

Official study title

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

Acronym: VRP-034

Important dates

Study start
2026
Primary completion
2026
Study completion
2026
First posted
Mar 30, 2026
Registry last updated
Mar 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.