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.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 48
- 试验地点
- 1
研究概览
简要总结
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 equivalent 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- Male
入选标准
- •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 kgm2, 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.
排除标准
- •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 Details mentioned in the approved protocol.
研究者
Dr Hiren Prajapati
Veeda Clinical Research Ltd