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

NCT03690362 | Completed Phase 1 FDA Drug

• 3 other identifiers: VNRX-5133-104272201300019C-12-0-317-0103
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (5)

Group 1 - Control

EXPERIMENTAL

Healthy control subjects will be matched by gender, weight, and age to subjects with renal impairment

Drug: VNRX-5133 and VNRX-5022

Group 2 - Mild Renal Impairment

EXPERIMENTAL

Mild renal impairment

Drug: VNRX-5133 and VNRX-5022

Group 3 - Moderate Renal Impairment

EXPERIMENTAL

Moderate Renal Impairment

Drug: VNRX-5133 and VNRX-5022

Group 4 - Severe Renal Impairment

EXPERIMENTAL

Severe Renal Impairment

Drug: VNRX-5133 and VNRX-5022

Group 5 - ESRD

EXPERIMENTAL

End Stage Renal Disease undergoing chronic intermittent hemodialysis

Drug: VNRX-5133 and VNRX-5022

Interventions

VNRX-5133 and VNRX-5022 DRUG

intravenous infusion

Group 1 - Control; Group 2 - Mild Renal Impairment; Group 3 - Moderate Renal Impairment; Group 4 - Severe Renal Impairment; Group 5 - ESRD

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Venatorx Pharmaceuticals, Inc.: lead
• National Institutes of Health (NIH): collaborator

Study Sites (2)

Orlando Cliniical Research Associates

Orlando, Florida, 32809, United States

Location

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

Related Publications (1)

• 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.

  PMID: 35920662 DERIVED

MeSH Terms

Interventions

taniborbactam

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will enroll approximately 32 subjects assigned to treatment groups based on renal function.

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: October 1, 2018
• Study Start: April 6, 2018
• Primary Completion: November 21, 2018
• Study Completion: November 21, 2018
• Last Updated: February 8, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)