VNRX-7145 Drug-Drug Interaction in Healthy Adult Volunteers

Study Overview
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Brief Summary
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This study will provide an initial assessment of the safety and PK of VNRX-7145 and VNRX-5024 (ceftibuten) when administered as single agents and with co-administration in a single dose cross-over design in Part 1. In Part 2, subjects will receive 500 mg of VNRX-7145 or matching placebo q8h for 10 days. VNRX-7145 and VNRX-5024 (ceftibuten) will be administered every 8 hours (q8h) for 10 days at 2 dose levels of VNRX-7145 in Part 3.

Official Title
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VNRX-7145-102: A Randomized, Drug-Drug Interaction Study to Assess the Safety and Pharmacokinetics (PK) of VNRX-7145 and VNRX-5024 (Ceftibuten) in Healthy Adult Volunteers

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: VNRX-7145
* Drug: VNRX-5024 (ceftibuten)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults 18-55 years Males or non-pregnant, non-lactating females Body mass index (BMI): ≥18.5 kg/m2 and ≤32.0 kg/m2 Normal blood pressure Normal lab tests Exclusion Criteria: History or presence of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, autoimmune, hematologic, neoplastic, or neurological disorders History of drug allergy or hypersensitivity to penicillin, cephalosporin, or beta-lactam antibacterial drug Use of antacid medications Abnormal ECG or history of clinically significant abnormal rhythm disorder Positive alcohol, drug, or tobacco use/test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1: Crossover Parts 2&3: Parallel
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Subjects will receive single doses of VNRX-7145 or VNRX-5024 alone and in combination. All subjects will receive study drug in the sequence specified by the randomization schedule. | Drug: VNRX-7145<br>* β-lactamase inhibitor<br>Drug: VNRX-5024 (ceftibuten)<br>* β-lactam antibiotic<br>|
| Experimental: Part 2A<br>Multiple dose administration of VNRX-7145 q8h for 10 days | Drug: VNRX-7145<br>* β-lactamase inhibitor<br>|
| Placebo Comparator: Part 2B<br>Multiple dose administration of placebo q8h for 10 days | Drug: Placebo<br>* Placebo<br>|
| Experimental: Part 3A<br>Multiple dose administration of low dose VNRX-7145 + VNRX-5024 | Drug: VNRX-7145<br>* β-lactamase inhibitor<br>Drug: VNRX-5024 (ceftibuten)<br>* β-lactam antibiotic<br>|
| Experimental: Part 3B<br>Multiple dose administration of high dose VNRX-7145 + VNRX-5024 | Drug: VNRX-7145<br>* β-lactamase inhibitor<br>Drug: VNRX-5024 (ceftibuten)<br>* β-lactam antibiotic<br>|
| Placebo Comparator: Part 3C<br>Multiple dose administration of Placebo (matching VNRX-7145 + VNRX-5024) | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Cmax | concentration time data | 0-48 hours | 
| Part 1: AUC0-inf | Area under the concentration-time curve from time-zero extrapolated to infinity based on collected PK | 0-48 hours | 
| Parts 2&3: Number of subjects with adverse events |  | Day 15 (+2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of subjects with adverse events |  | Day 14 (+2) | 
| Parts 2&3: AUC0-tau |  | Day 1 | 
| Parts 2&3: AUC0-tau |  | Day 10 | 
| Parts 2&3: Cmax |  | Day 1 | 
| Parts 2&3: Cmax |  | Day 10 |