The Study is Designed to Evaluate Single Ascending Doses of AR882 in Healthy Adult Males

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled, single ascending dose study of AR882 in healthy adult males.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Rising Dose Study of AR882, a Potent Uricosuric Agent, in Healthy Adult Male Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Cohort 1: AR882
* Drug: Cohort 2: AR882
* Drug: Cohort 3: AR882
* Drug: Cohort 4: AR882
* Drug: Cohort 5: AR882
* Drug: Cohort 6: AR882 Food Effect
* Drug: Cohort 7: AR882 Solid Oral Formulation
* Drug: Cohort 8: AR882 in combination with allopurinol
* Drug: Cohort 9: AR882 in combination with febuxostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Serum uric acid level ≥ 4.5 mg/dL (268 µmol/L) Body weight no less than 50 kg and body mass index (BMI) within the range of ≥18 and ≤33 kg/m2 Must be free of any clinically significant disease that requires a physician's care and/or would interfere with study evaluations or procedures Exclusion Criteria: Malignancy within 5 years, except for successfully treated basal or squamous cell carcinoma of the skin History of cardiac abnormalities History and/or presence of drug addiction or excessive use of alcohol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AR882 (Dose A)<br> | Drug: Cohort 1: AR882<br>* Single dose of AR882 or matching placebo<br>|
| Experimental: AR882 (Dose B)<br> | Drug: Cohort 2: AR882<br>* Single dose of AR882 or matching placebo<br>Drug: Cohort 6: AR882 Food Effect<br>* Single dose of AR882 or matching placebo in a fed state<br>Drug: Cohort 8: AR882 in combination with allopurinol<br>* Single dose of allopurinol alone and a single dose of AR882 in combination with a single dose of allopurinol<br>Drug: Cohort 9: AR882 in combination with febuxostat<br>* Single dose of febuxostat alone and a single dose of AR882 in combination with a single dose of febuxostat<br>|
| Experimental: AR882 (Dose C)<br> | Drug: Cohort 3: AR882<br>* Single dose of AR882 or matching placebo<br>|
| Experimental: AR882 (Dose D)<br> | Drug: Cohort 4: AR882<br>* Single dose of AR882 or matching placebo<br>|
| Experimental: AR882 (Dose E)<br> | Drug: Cohort 5: AR882<br>* Single dose of AR882 or matching placebo<br>|
| Experimental: AR882 (Dose B) Solid Oral Formulation<br> | Drug: Cohort 7: AR882 Solid Oral Formulation<br>* Single dose of AR882 or matching placebo<br>|
| Placebo Comparator: Placebo<br> | Drug: Cohort 1: AR882<br>* Single dose of AR882 or matching placebo<br>Drug: Cohort 2: AR882<br>* Single dose of AR882 or matching placebo<br>Drug: Cohort 3: AR882<br>* Single dose of AR882 or matching placebo<br>Drug: Cohort 4: AR882<br>* Single dose of AR882 or matching placebo<br>Drug: Cohort 5: AR882<br>* Single dose of AR882 or matching placebo<br>Drug: Cohort 6: AR882 Food Effect<br>* Single dose of AR882 or matching placebo in a fed state<br>Drug: Cohort 7: AR882 Solid Oral Formulation<br>* Single dose of AR882 or matching placebo<br>|
| Active Comparator: Allopurinol<br> | Drug: Cohort 8: AR882 in combination with allopurinol<br>* Single dose of allopurinol alone and a single dose of AR882 in combination with a single dose of allopurinol<br>|
| Active Comparator: Febuxostat<br> | Drug: Cohort 9: AR882 in combination with febuxostat<br>* Single dose of febuxostat alone and a single dose of AR882 in combination with a single dose of febuxostat<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety profile of AR882 based on incidence of abnormal laboratory findings | Analysis of abnormal safety laboratory findings | 8 Days | 
| Safety Analyses | ECG Heart Rate | 8 Days | 
| Safety Analyses | ECG PR-Interval | 8 Days | 
| Safety Analyses | ECG RR-Interval | 8 Days | 
| Safety Analyses | ECG QRS-Interval | 8 Days | 
| Safety Analyses | ECG QT-Interval | 8 Days | 
| Safety Analyses | ECG QTc-Interval | 8 Days | 
| Safety Analyses | Vital Sign - Systolic Blood Pressure | 8 Days | 
| Safety Analyses | Vital Sign - Diastolic Blood Pressure | 8 Days | 
| Safety Analyses | Vital Sign - Pulse Rate | 8 Days | 
| Safety Analyses | Vital Sign - Body Temperature | 8 Days | 
| Safety Analyses | Vital Sign - Respiratory Rate | 8 Days | 
| Area under the curve (AUC) for plasma AR882 | Profile from plasma in terms of AUC for AR882 | 6 Days | 
| Time to maximum plasma concentration (Tmax) for AR882 | Profile from plasma in terms of Tmax for AR882 | 6 Days | 
| Maximum plasma concentration (Cmax) for AR882 | Profile from plasma in terms of Cmax for AR882 | 6 Days | 
| Apparent terminal half-life (t1/2) for AR882 | Profile from plasma in terms of t1/2 for AR882 | 6 Days | 
| Amount excreted (Ae) into urine for AR882 | Profile from urine in terms of Ae for AR882 | 6 Days | 
| Fractional Excretion (FEUA) for AR882 | Profile from urine in terms of FEUA for AR882 | 6 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PD profile of a single dose of AR882 | Profile from serum uric acid concentrations over time | 6 Days | 
| PD profile of a single dose of AR882 in combination with allopurinol | Profile from serum uric acid concentrations over time | 6 Days | 
| PD profile of a single dose of AR882 in combination with febuxostat | Profile from serum uric acid concentrations over time | 6 Days |