RDEA3170 Bioavailability Study

Study Overview
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Brief Summary
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This is a Phase 1, randomized, open-label, 4-way crossover pharmacokinetic (PK) and pharmacodynamic (PD) study in healthy adult male subjects designed to assess the relative bioavailability of RDEA3170 2.5 mg tablets administered as a 10 mg dose (2.5 mg × 4 tablets) and of a single RDEA3170 10 mg tablet. This study will also assess the effect of a low-fat and high-fat meal on the PK and PD of RDEA3170 10 mg tablets.

Official Title
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A Phase 1, Randomized, Open-Label, Crossover Study in Healthy Adult Male Subjects to Assess the Relative Bioavailability of Two RDEA3170 Tablets

Conditions
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Gout

Intervention / Treatment
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* Drug: RDEA3170 10 mg
* Drug: RDEA3170 2.5 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is able to understand the study procedures and the risks involved and is willing to provide written informed consent before the first study-related activity Subject has a body weight ≥ 50 kg (110 lbs.) and a body mass index ≥ 18 and ≤ 40 kg/m2 Subject has a Screening serum urate level ≤ 7 mg/dL Subject is free of any clinically significant disease or medical condition, per the Investigator's judgment Exclusion Criteria: Subject has a history or suspicion of kidney stones Subject has undergone major surgery within 3 months prior to Screening Subject donated blood or experienced significant blood loss (> 450 mL) within 12 weeks prior to Day 1 or gave a plasma donation within 4 weeks prior to Day 1 Subject has inadequate venous access or unsuitable veins for repeated venipuncture Subject has a Screening serum creatinine value above the upper limit of normal during Screening or at Day -2 (Admission) Subject cannot swallow multiple tablets Subject is a heavy caffeine drinker Subject is unwilling to comply with the dietary restrictions of the study Subject is unable or unwilling to comply with the study requirements or has a situation or condition that, in the opinion of the Investigator, may interfere with participation in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence ABCD<br>2.5 mg x 4 tablets qd (once daily) fasted, 10 mg tablet qd fasted, 10 mg tablet qd fed low-fat, 10 mg tablet qd fed high-fat. | Drug: RDEA3170 10 mg<br> <br> Drug: RDEA3170 2.5 mg<br> <br> |
| Experimental: Sequence BACD<br>10 mg tablet qd fasted, 2.5 mg x 4 tablets qd fasted, 10 mg tablet qd fed low-fat, 10 mg tablet qd fed high-fat | Drug: RDEA3170 10 mg<br> <br> Drug: RDEA3170 2.5 mg<br> <br> |
| Experimental: Sequence ABDC<br>2.5 x 4 mg tablets qd fasted, 10 mg tablet qd fasted, 10 mg tablet qd fed high-fat, 10 mg tablet qd fed low-fat | Drug: RDEA3170 10 mg<br> <br> Drug: RDEA3170 2.5 mg<br> <br> |
| Experimental: Sequence BADC<br>10 mg tablet qd fasted, 2.5 mg x 4 tablets qd fasted, 10 mg tablet qd fed high-fat, 10 mg tablet qd fed low-fat | Drug: RDEA3170 10 mg<br> <br> Drug: RDEA3170 2.5 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Cmax of RDEA3170 in fasted condition. | Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax of RDEA3170 following various treatments. | Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| Area Under the Concentration-time Curve From Time Zero to the Quantifiable Last Sampling Timepoint (AUC Last) | AUC last of RDEA3170 in fasted condition. | Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| Area Under the Concentration-time Curve From 0 to Infinity (AUC∞) | AUC∞ of RDEA3170 the fasted condition. | Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| Apparent Terminal Half-life (t1/2) | t1/2 of RDEA3170 following various treatments. | Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| Cmax: Effect of High Fat Meal on the PK of RDEA3170 Tablets | Cmax of RDEA3170 in high-fat fed state. | Days 1 to 13 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| AUC Last: Effect of High Fat Meal on the PK of RDEA3170 Tablets | AUC last of RDEA3170 in high-fat fed state. | Days 1 to 13 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| AUC∞: Effect of High Fat Meal on the PK of RDEA3170 Tablets | AUC∞ of RDEA3170 in high-fat fed state. | Days 1 to 13 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| Cmax: Effect of Low Fat Meal on the PK of RDEA3170 Tablets | Cmax of RDEA3170 in low-fat fed state. | Days 1 to 9 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| AUC Last: Effect of Low Fat Meal on the PK of RDEA3170 Tablets | AUC last of RDEA3170 in low-fat fed state. | Days 1 to 9 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 
| AUC∞: Effect of Low Fat Meal on the PK of RDEA3170 Tablets | AUC∞ of RDEA3170 in low-fat fed state. | Days 1 to 9 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose Pharmacodynamics (PD) Profile of RDEA3170 From Serum and Urine | PD profiles of uric acid from serum and urine. PD parameters were evaluated to assess whether any potential differences in PK for the 2 different tablets resulted in differences in uric acid excretion. | Day -1: -24, -23, -22, -21, -20, -18, -16, -14, and -12 hours predose. Days 1, 5, 9, and 13: predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose. | 
| Incidence of Treatment-Emergent Adverse Events |  | 7 weeks. |