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

Sponsor: Venus Remedies Limited

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.

Official 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

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