VNRX-5133 With VNRX-5022 in Subjects With Varying Degrees of Renal Impairment

Study Overview
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Brief Summary
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This is a multi-center, open-label, PK and safety study of VNRX-5133 and VNRX-5022 when co-administered in male and female subjects with varying levels of renal impairment and healthy normal controls.

Official Title
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A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VNRX-5133 With VNRX-5022 in Subjects With Varying Degrees of Renal Impairment

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: VNRX-5133 and VNRX-5022


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI: 18.5-40.0 kg/m2 with a minimum weight of 45 kg Able and willing to abstain from alcohol from 48 h before admission until the follow-up visit Suitable veins for cannulation/multiple venipunctures, as assessed by the Investigator at Screening Males who are not surgically sterilized and females of childbearing potential must agree to use highly effective methods of contraception during the study and for 90 days after study drug administration. Laboratory values meeting defined entry criteria Subjects with normal renal function (Group 1) must also meet the following criteria: Match to one or more subjects with renal impairment by gender, age, and weight Subjects with renal impairment (Groups 2-5) must also meet the following criteria: Stable, pre-existing renal impairment. Exclusion Criteria: Employee of the study site, Contract Research Organization (CRO) or the IND Sponsor Female who is pregnant, lactating, or planning to attempt to become pregnant during the study or within 90 days after study drug administration Male with a female partner who is pregnant or lactating during the study, or planning to attempt to become pregnant during the study or within 90 days after study drug administration Use of any investigational drug or device within 30 days before study drug administration (90 days for an injectable biological agent) The subject has a congenital or acquired immunodeficiency syndrome Screening or Day -1, clinically significant abnormal ECG values Active malignancy; exceptions are permitted for carcinoma in situ of the prostate or the skin (basal cell or squamous cell) are permitted History of drug allergy of a severity that required urgent medical treatment, such as treatment with epinephrine in an Emergency Department Known immediate hypersensitivity reaction following administration of a cephalosporin, penicillin, or other β-lactam antibacterial drug History of donation of more than 450 mL of blood within 60 days before dosing in the site or planned donation before 30 days has elapsed since ingestion of study drug Plasma or platelet donation within 7 days of dosing and throughout the study Consumes more than 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of hard liquor) or has a significant history of alcohol abuse or drug/chemical abuse within the last 1 year Oral temperature >38.5˚C or acute illness on Day -1 Previous participation in a study of VNRX-5133 Excluded concomitant medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: The study will enroll approximately 32 subjects assigned to treatment groups based on renal function.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - Control<br>Healthy control subjects will be matched by gender, weight, and age to subjects with renal impairment | Drug: VNRX-5133 and VNRX-5022<br>* intravenous infusion<br>|
| Experimental: Group 2 - Mild Renal Impairment<br>Mild renal impairment | Drug: VNRX-5133 and VNRX-5022<br>* intravenous infusion<br>|
| Experimental: Group 3 - Moderate Renal Impairment<br>Moderate Renal Impairment | Drug: VNRX-5133 and VNRX-5022<br>* intravenous infusion<br>|
| Experimental: Group 4 - Severe Renal Impairment<br>Severe Renal Impairment | Drug: VNRX-5133 and VNRX-5022<br>* intravenous infusion<br>|
| Experimental: Group 5 - ESRD<br>End Stage Renal Disease undergoing chronic intermittent hemodialysis | Drug: VNRX-5133 and VNRX-5022<br>* intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | To assess the pharmacokinetics of VNRX-5133 and VNRX-5022 in combination by assessment of Cmax | 72 hours | 
| Area under the plasma concentration versus time curve (AUC) | To assess the pharmacokinetics of VNRX-5133 and VNRX-5022 in combination by assessment of AUC | 72 hours | 
| Safety and tolerability of VNRX-5133 and VNRX-5022 measured as number of subjects with adverse events. | Number of Subjects with AEs (Assessed via patient report, physical exam, ECGs, vital signs, laboratory investigations, and use of concomitant medications for the treatment of AEs) | 8 Days |