ANX-188 Thorough QT/QTc Study in Healthy Volunteers

Study Overview
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Brief Summary
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This study has been designed in compliance with the ICH-E14 guideline (2005) to evaluate the effect of ANX-188 at therapeutic and supratherapeutic concentrations on cardiac repolarization, specifically, Fridericia's QT-Interval (QTcF)

Official Title
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A Four Period, Four-Arm, Crossover Design, Randomized, Placebo and Active Controlled Study for the Evaluation of the Effect of Therapeutic and Supratherapeutic Single-Dose ANX-188 on the QT/QTc Intervals in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: ANX-188 Therapeutic Dose
* Drug: ANX-188 Supratherapeutic dose
* Drug: Saline
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects aged 18 to 65 (inclusive) in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory testing at screening. Exclusion Criteria: Participation in a clinical trial within the last 60 days Pregnant or lactating females Use of prescription drugs, herbals, or over-the-counter medications within 14 days prior to study day -2 Uncontrolled cardiac arrhythmias, cardiac valve abnormalities, or not in normal sinus rhythm Smokers or tobacco product user in the prior 3 months Presence of clinically significant illness Other protocol defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANX-188 Therapeutic dose level<br>IV administration. 100 mg/kg for one hour followed by 30 mg/kg/hour for five hours | Drug: ANX-188 Therapeutic Dose<br> <br> * Other names: vepoloxamer;|
| Experimental: ANX-188 Supratherapeutic dose<br>IV administration. 300 mg/kg for one hour followed by 200 mg/kg/hr for five hours | Drug: ANX-188 Supratherapeutic dose<br> <br> * Other names: vepoloxamer;|
| Placebo Comparator: Saline<br>IV administration. Six hour infusion. | Drug: Saline<br> <br> * Other names: Placebo Comparator;|
| Active Comparator: Moxifloxacin<br>Oral tablet. 400 mg. | Drug: Moxifloxacin<br> <br> * Other names: Active Comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effect of therapeutic and supratherapeutic doses of ANX-188 on cardiac ventricular repolarization, specifically, the Fridericia's corrected QT-Interval (QTcF) |  | Day 1 Pre-dose to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bazett's corrected QT-interval (QTcB) |  | Pre-dose to 24 hours post-dose | 
| Heart rate measurements on treatment compared to time-matched baseline and placebo |  | Pre-dose to 24 hours post-dose | 
| RR-interval on treatment compared to time-matched baseline and placebo |  | Pre-dose to 24 hours post-dose | 
| QRS measurements on treatment compared to time-matched baseline and placebo |  | Pre-dose to 24 hours post-dose | 
| PR interval measurements on treatment compared to time-matched baseline and placebo |  | Pre-dose to 24 hours post-dose | 
| Overall characterization of normal and abnormal ECGs and the number and percentage of subjects with normal and abnormal ECGs |  | Pre-dose to 24 hours post-dose | 
| Number and percentage of subjects that develop abnormalities of repolarization on treatment |  | Pre-dose to 24 hours post-dose | 
| Number and percentage of subjects the develop abnormal U waves |  | Pre-dose to 24 hours post-dose | 
| Relationship between changes from the baseline and placebo in QTcF (DDQTcF) |  | Pre-dose to 24 hours post-dose | 
| Analysis for arrhythmias |  | Pre-dose to 24 hours post-dsoe | 
| Correlation of ECG findings with clinical adverse events |  | Pre-dose to 24 hours post-dose |