Mild, Moderate and Severe Renal Impairment Study

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

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.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Drug: RDEA3170

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
  • Florida
    • Orlando, Florida, United States, 32809
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
  • Tennessee
    • Knoxville, Tennessee, United States, 37920

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Mild renal impairment; RDEA3170 15 mg once daily fasted	Drug: RDEA3170
Experimental: Cohort 2: Moderate renal impairment; RDEA3170 15 mg once daily fasted	Drug: RDEA3170
Experimental: Cohort 3: Severe renal impairment; RDEA3170 15 mg once daily fasted	Drug: RDEA3170
Experimental: Cohort 4: Control subjects with normal renal function; RDEA3170 15 mg once daily fasted	Drug: RDEA3170

What is the study measuring?

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	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)

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.
• Investigators: Study Director: J. Hall, MD, Ardea Biosciences, Inc.

Publications and helpful links

General Publications

• Smith WB, Hall J, Berg JK, Kazimir M, Yamamoto A, Walker S, Lee CA, Shen Z, Wilson DM, Zhou D, Gillen M, Marbury TC. Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Verinurad, a Selective Uric Acid Reabsorption Inhibitor. Clin Drug Investig. 2018 Aug;38(8):703-713. doi: 10.1007/s40261-018-0652-2.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): October 30, 2015
• Study Completion (Actual): May 13, 2016

Study Registration Dates

• First Submitted: August 15, 2014
• First Submitted That Met QC Criteria: August 18, 2014
• First Posted (Estimate): August 19, 2014

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: March 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Antirheumatic Agents; Gout Suppressants; Verinurad
• Other Study ID Numbers: RDEA3170-108