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

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

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.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: VNRX-5133 and VNRX-5022

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Cliniical Research Associates
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Venatorx Pharmaceuticals, Inc.
• Collaborators: National Institutes of Health (NIH)

Publications and helpful links

General Publications

• Dowell JA, Marbury TC, Smith WB, Henkel T. Safety and Pharmacokinetics of Taniborbactam (VNRX-5133) with Cefepime in Subjects with Various Degrees of Renal Impairment. Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0025322. doi: 10.1128/aac.00253-22. Epub 2022 Aug 3.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2018
• Primary Completion (Actual): November 21, 2018
• Study Completion (Actual): November 21, 2018

Study Registration Dates

• First Submitted: March 21, 2018
• First Submitted That Met QC Criteria: September 27, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Actual): February 8, 2019
• Last Update Submitted That Met QC Criteria: February 7, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: VNRX-5133-104; 272201300019C-12-0-3 (U.S. NIH Grant/Contract); 17-0103 (Other Identifier: DMID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No