Study of the Safety, Tolerability, and PK of MRX-8 Administered Intravenously to HVs in SAD and MAD Cohorts

An Adaptive, Randomized, Double Blind, Placebo Controlled Three Part Study of the Safety, Tolerability, and Pharmacokinetics of MRX-8 Administered Intravenously to Healthy Volunteers in Single Ascending and Multiple Ascending Dose Cohorts

This Phase 1 study is designed to assess the safety and tolerability of single and multiple intravenous (IV) doses of MRX-8, to assess the pharmacokinetics of MRX-8 and its primary metabolite following single and multiple IV doses, and to measure the elimination of MRX-8 and its metabolite in urine.

Study Overview

• Status: Completed
• Conditions: Safety
• Intervention / Treatment: Drug: MRX-8; Drug: Placebo

Detailed Description

This is a first-in-human, randomized, double-blind, placebo-controlled study consisting of 3 parts. Part 1 will evaluate single ascending doses (SAD) of study drug. Part 2 will evaluate multiple ascending doses (MAD) of study drug administered for 7 days. Part 3 will evaluate MAD of study drug administered for 14 days.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Willing and able to provide written informed consent
• In good general health

Exclusion Criteria:

• Prior participation in a study utilizing a polymyxin or aminoglycoside antibiotic or other nephrotoxic drug within the 12 months prior to study drug administration on Day 1
• Use of tobacco or nicotine products, in any form, within 30 days prior to study drug administration on Day 1
• Venous access considered inadequate for IV infusions, laboratory safety assessments, or PK sample collection
• Underlying hepatic, renal, metabolic, cardiovascular or immunologic disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single intravenous doses of MRX-8; Single escalating doses of MRX-8	Drug: MRX-8; novel semi-synthetic polymyxin B analog.
Placebo Comparator: Single intravenous doses of placebo; Single intravenous doses of placebo to match MRX-8	Drug: Placebo; 5% dextrose in water
Active Comparator: Multiple intravenous doses of MRX-8 for 7 days; Multiple ascending intravenous doses of MRX-8 every 12 hours for 7 days.	Drug: MRX-8; novel semi-synthetic polymyxin B analog.
Placebo Comparator: Multiple intravenous doses of placebo for 7 days; Multiple intravenous doses of placebo every 12 hours for 7 days to match MRX-8.	Drug: Placebo; 5% dextrose in water
Active Comparator: Multiple intravenous doses of MRX-8 for 14 days; Multiple ascending intravenous doses of MRX-8 every 12 hours for 14 days.	Drug: MRX-8; novel semi-synthetic polymyxin B analog.
Placebo Comparator: Multiple intravenous doses of placebo for 14 days; Multiple intravenous doses of placebo every 12 hours for 14 days to match MRX-8.	Drug: Placebo; 5% dextrose in water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Symptoms reported by subjects.	Pre-dose through 48 hours after the end of infusion on the final infusion of study drug
Clinical laboratory assessment	Complete blood count	Pre-dose through 48 hours after the end of infusion on the final infusion of study drug
Peak Plasma Concentration (Cmax)	Cmax of MRX-8 and its primary metabolite following single and multiple intravenous doses	Pre-dose through 48 hours after the end of infusion on the final infusion of study drug
Time to Peak Plasma Concentration (Tmax)	Tmax of MRX-8 and its primary metabolite following single and multiple intravenous doses	Pre-dose through 48 hours after the end of infusion on the final infusion of study drug
Area under the plasma concentration versus time curve (AUC)	AUC of MRX-8 and its primary metabolite following single and multiple intravenous doses	Pre-dose through 48 hours after the end of infusion on the final infusion of study drug
Vital signs	Heart rate	Pre-dose through 48 hours after the end of infusion on the final infusion of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elimination of MRX-8 and its primary metabolite in urine	Quantity of measurable MRX-8 and its primary metabolite excreted in urine	At the end of infusion through 24 hours after the end of infusion on the final infusion of study drug

Collaborators and Investigators

• Sponsor: MicuRx
• Collaborators: Wellcome Trust; Biomedical Advanced Research and Development Authority

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2020
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 25, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: MRX8-101

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