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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Safety

Intervention / Treatment
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* Drug: MRX-8
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |