Ceftibuten/VNRX-7145 in Participants With Varying Degrees of Renal Function

Study Overview
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Brief Summary
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This is an open-label, multicenter, parallel-group study in participants with normal renal function, mild, moderate, or severe renal impairment, or end stage renal disease (ESRD) undergoing standard intermittent dialysis. The pharmacokinetics (PK) of the inactive prodrug VNRX-7145, its active parent drug VNRX-5236, and ceftibuten will be evaluated after a single oral dose of ceftibuten/VNRX-7145.

Official Title
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VNRX-7145-103: A Phase 1, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Ceftibuten/VNRX-7145 in Participants With Varying Degrees of Renal Function

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: VNRX-7145
* Drug: Ceftibuten


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults 18-82 years Males or non-pregnant, non-lactating females Body mass index (BMI): ≥18.5 kg/m2 and ≤40.0 kg/m2 Laboratory values meeting defined entry criteria Subjects with normal renal function (Group 1) must also meet the following criteria: • Match to one or more participants with renal impairment by gender, age, and BMI Subjects with renal impairment (Groups 2-5) must also meet the following criteria: • Stable, pre-existing renal impairment Exclusion Criteria: History of drug allergy or hypersensitivity to penicillin, cephalosporin, or beta-lactam antibacterial drug Congenital or acquired immunodeficiency syndrome Major adverse cardiovascular event within one year of dosing Positive alcohol, drug, or tobacco use/test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 82 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: Parallel Assignment
Interventional Model Description: The study will enroll approximately 32 participants assigned to groups based on renal function.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - Control<br>Healthy control participants will be matched by gender, age, and BMI to participants with renal impairment | Drug: VNRX-7145<br>* single oral dose<br>Drug: Ceftibuten<br>* single oral dose<br>|
| Experimental: Group 2 - Mild Renal Impairment<br>Mild Renal Impairment | Drug: VNRX-7145<br>* single oral dose<br>Drug: Ceftibuten<br>* single oral dose<br>|
| Experimental: Group 3 - Moderate Renal Impairment<br>Moderate Renal Impairment | Drug: VNRX-7145<br>* single oral dose<br>Drug: Ceftibuten<br>* single oral dose<br>|
| Experimental: Group 4 - Severe Renal Impairment<br>Severe Renal Impairment | Drug: VNRX-7145<br>* single oral dose<br>Drug: Ceftibuten<br>* single oral dose<br>|
| Experimental: Group 5 - End Stage Renal Disease<br>End Stage Renal Disease undergoing chronic intermittent hemodialysis | Drug: VNRX-7145<br>* single oral dose<br>Drug: Ceftibuten<br>* single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum plasma concentration, determined directly from individual concentration time data | 0-120 hours post dose | 
| AUC0-inf | Area under the plasma concentration time curve from time zero extrapolated to infinity based on collected PK | 0-120 hours post dose | 
| Number of subjects with adverse events |  | 8 days post dose |