Mild, Moderate and Severe Renal Impairment Study

NCT02219516 | Completed Phase 1 Results

• 1 other identifier: RDEA3170-108
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 4

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.

Conditions

Gout

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (2)

• 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)

Study Arms (4)

Cohort 1: Mild renal impairment

EXPERIMENTAL

RDEA3170 15 mg once daily fasted

Drug: RDEA3170

Cohort 2: Moderate renal impairment

EXPERIMENTAL

RDEA3170 15 mg once daily fasted

Drug: RDEA3170

Cohort 3: Severe renal impairment

EXPERIMENTAL

RDEA3170 15 mg once daily fasted

Drug: RDEA3170

Cohort 4: Control subjects with normal renal function

EXPERIMENTAL

RDEA3170 15 mg once daily fasted

Drug: RDEA3170

Interventions

RDEA3170 DRUG

Cohort 1: Mild renal impairment; Cohort 2: Moderate renal impairment; Cohort 3: Severe renal impairment; Cohort 4: Control subjects with normal renal function

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ardea Biosciences, Inc.: lead

Study Sites (4)

Unknown Facility

Lakewood, Colorado, 80228, United States

Location

Unknown Facility

Orlando, Florida, 32809, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55404, United States

Location

Unknown Facility

Knoxville, Tennessee, 37920, United States

Location

Related Publications (1)

• 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.

  PMID: 29949102 DERIVED

MeSH Terms

Conditions

Gout

Interventions

verinurad

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Jesse Hall, MD
• Organization: Study Information Center AstraZeneca

information.center@astrazeneca.com

+1 877-240-9479

Study Officials

• J. Hall, MD

  Ardea Biosciences, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2014
• First Posted: August 19, 2014
• Study Start: August 1, 2014
• Primary Completion: October 30, 2015
• Study Completion: May 13, 2016
• Last Updated: April 25, 2017
• Results First Posted: April 25, 2017

Record last verified: 2017-03

Locations

US (4)