Mild, Moderate and Severe Renal Impairment Study

Study Overview
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Brief Summary
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This is a Phase 1, single-dose, open-label, pharmacokinetic (PK) and pharmacodynamic (PD) study of RDEA3170 in adult male subjects with mild, moderate, and severe renal impairment.

Official Title
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A Phase 1, Single-Dose, Open Label, Pharmacokinetic and Pharmacodynamic Study of RDEA3170 in Adult Male Subjects With Mild, Moderate, and Severe Renal Impairment

Conditions
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Gout

Intervention / Treatment
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* Drug: RDEA3170


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a body weight ≥ 50 kg (110 lbs.) and a body mass index ≥ 18 and ≤ 40 kg/m2. Subject with renal impairment, as determined at Screening, with creatinine clearance as calculated by the Cockcroft-Gault formula of 60 to < 90 mL/min (mild impairment), 30 to < 60 mL/min (moderate impairment), or 15 to < 30 mL/min (severe impairment), or a matched control subject (by age and body mass index) with a creatinine clearance of ≥ 90 mL/min. Subject has a Screening serum urate level ≥ 4.5 mg/dL and ≤ 10 mg/dL Exclusion Criteria: Subject has a history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders. Subject has a history or suspicion of kidney stones. Subject has a history of asthma. Subject has undergone major surgery within 3 months prior to Day 1. Subject has donated blood or experienced significant blood loss (> 450 mL) within 12 weeks prior to Day 1 or gave a plasma donation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Mild renal impairment<br>RDEA3170 15 mg once daily fasted | Drug: RDEA3170<br> <br> |
| Experimental: Cohort 2: Moderate renal impairment<br>RDEA3170 15 mg once daily fasted | Drug: RDEA3170<br> <br> |
| Experimental: Cohort 3: Severe renal impairment<br>RDEA3170 15 mg once daily fasted | Drug: RDEA3170<br> <br> |
| Experimental: Cohort 4: Control subjects with normal renal function<br>RDEA3170 15 mg once daily fasted | Drug: RDEA3170<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 following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose | 
| Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose | 
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose | 
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) | AUC∞ following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose | 
| Apparent Terminal Half-life (t1/2) | t1/2 following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose | 
| Non-renal Clearance From Time 0 to 72 Hours Postdose (CLNR 0-72) | CLNR 0-72 following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose | 
| Total Body Clearance Corrected for Bioavailability (CL/F) | CL/F following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose | 
| Renal Clearance Time 0 to 72 Hours Postdose (CLR 0-72) | CLR 0-72 following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events |  | 5 weeks | 
| Pharmacodynamics (PD) Profiles of Uric Acid From Serum and Urine |  | Screening, Day -1 ( -24, -21, -18, -and -12 hours predose), and Day 1 (within 30 minutes prior to dosing and at 3, 6, 12, 24, 30, 36, 48, 54, 60, and 72 hours postdose) |