Clinical trial NCT02219516: Mild, Moderate and Severe Renal Impairment Study
Official title: A Phase 1, Single-Dose, Open Label, Pharmacokinetic and Pharmacodynamic Study of RDEA3170 in Adult Male Subjects With Mild, Moderate, and Severe Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gout
Lead sponsor: Ardea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2014-08-19
Enrollment: 31
Sex: MALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: Time of Occurrence of Maximum Observed Concentration (Tmax)
timeFrame: 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
measure: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞)
timeFrame: 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
measure: Apparent Terminal Half-life (t1/2)
timeFrame: 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
measure: Non-renal Clearance From Time 0 to 72 Hours Postdose (CLNR 0-72)
timeFrame: 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
measure: Total Body Clearance Corrected for Bioavailability (CL/F)
timeFrame: 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
measure: Renal Clearance Time 0 to 72 Hours Postdose (CLR 0-72)
timeFrame: 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 outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 5 weeks
measure: Pharmacodynamics (PD) Profiles of Uric Acid From Serum and Urine
timeFrame: 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)
Other outcomes:
Locations:
city: Lakewood
country: United States
state: Colorado
city: Orlando
country: United States
state: Florida
city: Minneapolis
country: United States
state: Minnesota
city: Knoxville
country: United States
state: Tennessee
Study officials:
affiliation: Ardea Biosciences, Inc.
name: J. Hall, MD
role: STUDY_DIRECTOR
References:
citation: 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.