Mild, Moderate and Severe Renal Impairment Study

Phase 1

Completed

• Conditions: Gout
• Interventions: Drug: RDEA3170

• Registration Number: NCT02219516
• Lead Sponsor: Ardea Biosciences, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-08-01
• Study First Submitted: 2014-08-15
• Study First Submitted QC: 2014-08-18
• Study First Posted: 2014-08-19
• Primary Completion: 2015-10-30
• Study Completion: 2016-05-13
• Status Verified: 2017-03
• Results First Submitted: 2017-03-14
• Results First Submitted QC: 2017-03-14
• Last Update Submitted: 2017-03-14
• Results First Posted: 2017-04-25
• Last Update Posted: 2017-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 31

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 4: Control subjects with normal renal function	RDEA3170	RDEA3170 15 mg once daily fasted
Cohort 2: Moderate renal impairment	RDEA3170	RDEA3170 15 mg once daily fasted
Cohort 3: Severe renal impairment	RDEA3170	RDEA3170 15 mg once daily fasted
Cohort 1: Mild renal impairment	RDEA3170	RDEA3170 15 mg once daily fasted

Primary Outcome Measures

Name	Time	Method
Time of Occurrence of Maximum Observed Concentration (Tmax)	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	Tmax following a single administration of RDEA3170 to subjects with various degrees of renal function
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)	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	AUC last following a single administration of RDEA3170 to subjects with various degrees of renal function
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞)	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	AUC∞ following a single administration of RDEA3170 to subjects with various degrees of renal function
Apparent Terminal Half-life (t1/2)	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	t1/2 following a single administration of RDEA3170 to subjects with various degrees of renal function
Non-renal Clearance From Time 0 to 72 Hours Postdose (CLNR 0-72)	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	CLNR 0-72 following a single administration of RDEA3170 to subjects with various degrees of renal function
Maximum Observed Plasma Concentration (Cmax)	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	Cmax following a single administration of RDEA3170 to subjects with various degrees of renal function
Total Body Clearance Corrected for Bioavailability (CL/F)	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	CL/F following a single administration of RDEA3170 to subjects with various degrees of renal function
Renal Clearance Time 0 to 72 Hours Postdose (CLR 0-72)	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	CLR 0-72 following a single administration of RDEA3170 to subjects with various degrees of renal function

Secondary Outcome Measures

Name	Time	Method
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)