Single Dose Escalation and Multiple Dose Escalation Trial of an Intravenous Formulation of MRX-4

Study Overview
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Brief Summary
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A Phase 1 study of the safety, tolerability, and pharmacokinetics of a new oxazolidinone antibiotic. In Part 1 cohorts of healthy adults will participate in a single dose escalation study of increasing intravenous doses of MRX-4. In Part 2 cohorts of healthy adults will participate in a multiple dose escalation study of increasing intravenous doses of MRX-4 given twice daily for ten days. Part 3 is a crossover study of oral MRX-4 versus a comparable intravenous dose of MRX-4 to determine bioavailability.

Official Title
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A Randomized, Double-Blind, Placebo Controlled Three-Part Study of the Safety, Tolerability, and Pharmacokinetics of MRX 4 Administered Intravenously to Healthy Volunteers in Single Ascending and Multiple Ascending Dose Cohorts, and Bioavailability of Oral MRX-4 Versus Intravenous Administration

Conditions
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Safety

Intervention / Treatment
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* Drug: Single intravenous doses of MRX-4
* Drug: Single intravenous doses of placebo
* Drug: Multiple intravenous doses of MRX-4
* Drug: Multiple intravenous doses of placebo
* Drug: Single dose of intravenous and oral MRX-4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects Exclusion Criteria: Underlying hepatic, renal, metabolic, hematologic, cardiovascular, or immunologic disorder

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 |
| --- | --- |
| Experimental: Single intravenous doses of MRX-4<br>Single escalating intravenous doses of MRX-4 from 150 mg to 1800 mg | Drug: Single intravenous doses of MRX-4<br>* Intravenous single escalating doses of MRX-4<br>|
| Placebo Comparator: Single intravenous doses of placebo<br>Single intravenous doses of placebo to match MRX-4 | Drug: Single intravenous doses of placebo<br>* Intravenous single doses of placebo to match MRX-4<br>|
| Active Comparator: Multiple intravenous doses of MRX-4<br>Twice daily escalating intravenous doses of MRX-4 for 10 days: 600 mg, 900 mg, 1200 mg, and 1500 mg | Drug: Multiple intravenous doses of MRX-4<br>* Multiple ascending doses of MRX-4 given intravenously twice daily for 10 days<br>|
| Placebo Comparator: Multiple intravenous doses of placebo<br>Twice daily intravenous doses of placebo to match MRX-4 for 10 days | Drug: Multiple intravenous doses of placebo<br>* Multiple doses of placebo to match MRX-4 given intravenously twice daily for 10 days<br>|
| Active Comparator: Single dose of intravenous and oral MRX-4<br>Crossover of single dose of intravenous and oral MRX-4 | Drug: Single dose of intravenous and oral MRX-4<br>* Crossover single dose of intravenous and oral MRX-4 given on Day 1 and Day 4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of single and multiple ascending doses of MRX-4 | Summary statistics of the number of subjects with changes in vital signs, physical examinations, clinical lab data, ecg parameters, and adverse events | Screening through end of study visit on Day 7 (Part 1), Day 17 (Part II) and Day 15 (Part III) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration time data for MRX-4 and its metabolites | Individual and mean plasma concentration time data for MRX-4 and its metabolites | Pre-dose through 72 hours post dose | 
| Bioavailability of MRX-I and other MRX-4 metabolites | Levels of MRX-4 and its metabolites in blood | Pre-dose through 72 hours post dose | 
| Comparison of the pharmacokinetics of oral versus intravenous MRX-4 and its metabolites | Levels of MRX-4 and its metabolites in blood | Pre-dose through 72 hours post dose | 
| Elimination of MRX-4 and its metabolites in the urine following single dose adminstration | Levels of MRX-4 and its metabolites in urine | Pre-dose through 72 hours post dose |