VNRX-5133 Drug-Drug Interaction in Healthy Adult Volunteers

Study Overview
=================
Brief Summary
-----------------
This is a 2-part, drug-drug interaction study to evaluate potential PK interactions after single doses in Part 1 and multiple doses in Part 2. In Part 1, subjects will receive single dose of 5 treatments in a cross-over design; in Part 2 subjects will receive treatment for 10 days.

Official Title
-----------------
VNRX-5133-103: A Randomized, Drug-Drug Interaction Study to Assess the Safety and Pharmacokinetics of VNRX-5133 in Healthy Adult Volunteers

Conditions
-----------------
Bacterial Infections

Intervention / Treatment
-----------------
* Drug: VNRX-5133
* Drug: VNRX-5022
* Drug: Metronidazole
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adults Males or non-pregnant, non-lactating females Body Mass Index (BMI) between 18.5 - 32.0, inclusive Weight greater than or equal to 50 kg Suitable veins for cannulation Exclusion Criteria: Employee of site or the sponsor Any disease that poses an unacceptable risk to participants Abnormal ECG Abnormal labs Abnormal vital signs Current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, autoimmune, hematologic, neoplastic, or neurological disorder Positive serology for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) type 1

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1: Cross-over Part 2: Parallel
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A<br>In Part 1A, subjects will receive single doses of VNRX-5133 and VNRX-5022 alone and in combination. All subjects will receive all treatments in the sequence specified by the randomization schedule.. | Drug: VNRX-5133<br>* β-lactamase inhibitor<br>Drug: VNRX-5022<br>* Approved β-lactam antibiotic<br>|
| Experimental: Part 1B<br>In part 1B, subjects from Part 1A will receive metronidazole with or without VNRX-5133 + VNRX-5022. All subjects will receive all treatments in the sequence specified by the randomization schedule. | Drug: VNRX-5133<br>* β-lactamase inhibitor<br>Drug: VNRX-5022<br>* Approved β-lactam antibiotic<br>Drug: Metronidazole<br>* Approved antibiotic and antiprotozoal medication<br>|
| Experimental: Part 2 - 2A<br>Multiple dose administration of Low Dose VNRX-5133 + VNRX-5022 | Drug: VNRX-5133<br>* β-lactamase inhibitor<br>Drug: VNRX-5022<br>* Approved β-lactam antibiotic<br>|
| Experimental: Part 2 - 2B<br>Multiple dose administration of High Dose VNRX-5133 + VNRX-5022 | Drug: VNRX-5133<br>* β-lactamase inhibitor<br>Drug: VNRX-5022<br>* Approved β-lactam antibiotic<br>|
| Placebo Comparator: Part 2 - 2C<br>Multiple dose administration of Placebo (matching VNRX-5133 + VNRX-5022) | Drug: Placebo<br>* Placebo (matching VNRX-5133 + VNRX-5022)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of VNRX-5133 and VNRX-5022 following single doses alone and in combination (Part 1A) | Cmax | 0-48 hours | 
| Area under the plasma concentration versus time curve (AUC) of VNRX-5133 and VNRX-5022 following single doses alone and in combination (Part 1A) | AUCinf | 0-48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of metronidazole, VNRX-5133, and VNRX-5022 (Part 1B) | Cmax | 0-48 hours | 
| Area under the plasma concentration versus time curve (AUC) of metronidazole, VNRX-5133, and VNRX-5022 (Part 1B) | AUCinf | 0-48 hours | 
| Number of Subjects with Treatment Emergent Adverse Events | TEAEs based on patient reporting, physical exams, collection of vital signs, ECGs and absolute values and changes over time of hematology, chemistry and urinalysis. | First dose to 7 days after last dose: Part 1: 20 days / Part 2: 17 days | 
| Accumulation of VNRX-5133 + VNRX-5022 following multiple dose administration | Trough concentration levels from Day 1 - Day 10 | Part 2: 10 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy Volunteers, Pharmacokinetics