VNRX-5133 Drug-Drug Interaction in Healthy Adult Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: VNRX-5133; Drug: VNRX-5022; Drug: Metronidazole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • PRAHS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1A; 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; β-lactamase inhibitor; Drug: VNRX-5022; Approved β-lactam antibiotic
EXPERIMENTAL: Part 1B; 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; β-lactamase inhibitor; Drug: VNRX-5022; Approved β-lactam antibiotic; Drug: Metronidazole; Approved antibiotic and antiprotozoal medication
EXPERIMENTAL: Part 2 - 2A; Multiple dose administration of Low Dose VNRX-5133 + VNRX-5022	Drug: VNRX-5133; β-lactamase inhibitor; Drug: VNRX-5022; Approved β-lactam antibiotic
EXPERIMENTAL: Part 2 - 2B; Multiple dose administration of High Dose VNRX-5133 + VNRX-5022	Drug: VNRX-5133; β-lactamase inhibitor; Drug: VNRX-5022; Approved β-lactam antibiotic
PLACEBO_COMPARATOR: Part 2 - 2C; Multiple dose administration of Placebo (matching VNRX-5133 + VNRX-5022)	Drug: Placebo; Placebo (matching VNRX-5133 + VNRX-5022)

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bactericidal titers (Part 2)	To evaluate serum and urine bactericidal activity at peak and trough concentrations following multiple dose administration of VNRX-5133 + VNRX-5022	10 days

Collaborators and Investigators

• Sponsor: Venatorx Pharmaceuticals, Inc.
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 24, 2017
• Primary Completion (ACTUAL): December 20, 2017
• Study Completion (ACTUAL): December 20, 2017

Study Registration Dates

• First Submitted: September 28, 2017
• First Submitted That Met QC Criteria: November 1, 2017
• First Posted (ACTUAL): November 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy Volunteers
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole
• Other Study ID Numbers: VNRX-5133-103; 272201300019C-3-0-1 (U.S. NIH Grant/Contract); 17-0068 (OTHER: 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