RDEA3170 and Febuxostat Drug Interaction Study

A Phase 1 Study to Evaluate the Potential Pharmacokinetic and Pharmacodynamic Interactions Between RDEA3170 and Febuxostat in Healthy Adult Male Subjects

This study will evaluate the potential pharmacokinetic (PK) and pharmacodynamic (PD) interaction between the XO inhibitor febuxostat and the investigational URAT1 inhibitor RDEA3170 and provide information for potential future clinical studies using this combination. Combination treatment using 2 drugs with different mechanisms of action may achieve improved response and may allow the use of lower doses, resulting in fewer side effects than the use of either drug alone.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: RDEA3170 10 mg; Drug: Febuxostat 40 mg; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 49007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• body weight ≥ 50 kg (110 lbs.) and a body mass index ≥ 18 and ≤ 40 kg/m2.
• no clinically relevant abnormalities in vital signs, ECG, physical examination or safety laboratory values, per the Investigator's judgment.
• a screening serum urate level ≥ 4.5 mg/dL.

Exclusion Criteria:

• history or suspicion of kidney stones.
• history of cardiac abnormalities as assessed during screening, including abnormal and clinically relevant electrocardiogram changes and/or family history of sudden death in otherwise healthy individual between the ages of 1 and 30 years.
• undergone major surgery within 3 months prior to Day 1.
• donated blood or experienced significant blood loss (> 450 mL) within 12 weeks prior to Day 1 or gave a plasma donation within 4 weeks prior to the Screening Period.
• inadequate venous access or unsuitable veins for repeated venipuncture.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Febuxostat; Days 1-7: febuxostat 40 mg qd. Days 8-14: RDEA3170 10 mg or placebo qd in combination with febuxostat 40 mg qd. Days 15-21: RDEA3170 10 mg or placebo qd.	Drug: RDEA3170 10 mg; RDEA3170 10 mg once daily (qd); Drug: Febuxostat 40 mg; Febuxostat 40 mg qd; Drug: placebo; placebo qd
EXPERIMENTAL: RDEA3170; Days 1-7: RDEA3170 10 mg or placebo qd. Days 8-14: RDEA3170 10 mg or placebo qd in combination with febuxostat 40 mg qd. Days 15-21: febuxostat 40 mg qd.	Drug: RDEA3170 10 mg; RDEA3170 10 mg once daily (qd); Drug: Febuxostat 40 mg; Febuxostat 40 mg qd; Drug: placebo; placebo qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK profile of RDEA3170 from plasma and urine and febuxostat from plasma	Profile from plasma and urine in terms of AUC, Tmax, Cmax, t1/2, Ae, and CLr AUC: area under the concentration-time curve; Tmax: time to maximum plasma concentration; Cmax: maximum plasma drug concentration; t1/2: apparent terminal half-life; Ae: amount excreted of unchanged drug into urine; CLr: renal clearance	Days -1 (urine only), 7, 14, 21 and Days 8, 15, 22 (plasma only)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD profile of RDEA3170 and febuxostat alone and in combination	Profile from serum and urine in terms of sUA concentration, renal clearance of uric acid, urine uric acid excretion amounts, and fractional excretion of uric acid. sUA: serum urate	Days -1, 7, 14, 21 and Days 8, 15, 22 (serum only)
Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters		8 weeks

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.

Publications and helpful links

General Publications

• Rekic D, Johansson S, Leander J. Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight. Clin Pharmacokinet. 2021 Mar;60(3):319-328. doi: 10.1007/s40262-020-00943-6. Epub 2020 Sep 19.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: June 18, 2013
• First Submitted That Met QC Criteria: June 20, 2013
• First Posted (ESTIMATE): June 21, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): January 9, 2014
• Last Update Submitted That Met QC Criteria: January 8, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antirheumatic Agents; Gout Suppressants; Febuxostat; Verinurad
• Other Study ID Numbers: RDEA3170-105