Clinical trial NCT02246673: RDEA3170 and Febuxostat Combination Study in Gout Subjects
Official title: A Phase 2a, Randomized, Open-Label Study to Evaluate the Pharmacodynamic Effects and Safety of RDEA3170 Administered in Combination With Febuxostat Compared to Febuxostat Administered Alone in Adult Subjects With Gout
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gout
Lead sponsor: Ardea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2014-09-23
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2a, randomized, open-label, multicenter study to assess the pharmacodynamic (PD) effects and safety of RDEA3170 administered in combination with febuxostat compared to febuxostat administered alone in adult subjects with gout.


Eligibility criteria: Inclusion Criteria:

* Able to understand the study procedures and the risks involved and is willing to provide written informed consent before the first study-related activity.
* Meets one or more criteria for the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of Acute Arthritis of Primary Gout.
* Body weight ≥ 50 kg (110 lbs) and a body mass index ≥ 18 and ≤ 45 kg/m2.
* Screening serum urate level ≥ 8 mg/dL.
* Free of any clinically significant disease or medical condition, per the Investigator's judgment.

Exclusion Criteria:

* Unable to take colchicine for gout flare prophylaxis.
* History or suspicion of kidney stones.
* Any gastrointestinal disorder that affects motility and/or absorption.
* Unstable angina, New York Heart Association class III or IV heart failure, ischemic heart disease, stroke, or deep venous thrombosis within 12 months prior to Day 1; or subject is currently receiving anticoagulants.
* Screening laboratory parameters that are outside the normal limits and are considered clinically significant by the Investigator.
* Estimated creatinine clearance \< 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight during the Screening period.
* Taking losartan, fenofibrate, guaifenesin, or sodium-glucose linked transporter-2 inhibitors; chronic and stable doses are permitted if doses are stable for at least 14 days prior to study medication dosing.
* Unable or unwilling to comply with the study requirements or has a situation or condition that, in the opinion of the Investigator, may interfere with participation in the study.

Primary outcomes:
measure: Serum Urate Maximum Percentage (%) Change (Emax, CB)
timeFrame: 28 days
measure: Urine Uric Acid % Change (0-24h) (Aeur, CB)
timeFrame: 28 days
measure: Renal Clearance of Uric Acid % Change (0-24h) (CLur, CB)
timeFrame: 28 days
measure: Fract. Excretion of Uric Acid % Change (0-24h) (FEUA, CB)
timeFrame: 28 days
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Days 7 to 28
measure: Time of Occurrence of Maximum Observed Concentration (Tmax)
timeFrame: Days 7 to 28
measure: Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)
timeFrame: Days 7 to 28
measure: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)
timeFrame: Days 7 to 28
measure: Apparent Terminal Half-life (t1/2)
timeFrame: Days 7 to 28
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Anaheim
country: United States
state: California
city: Glendale
country: United States
state: California
city: South Miami
country: United States
state: Florida
city: Overland Park
country: United States
state: Kansas
city: Overland Park
country: United States
state: Kansas
city: Dallas
country: United States
state: Texas
Study officials:
affiliation: Ardea Biosciences, Inc.
name: J. Hall
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Fleischmann R, Winkle P, Hall J, Valdez S, Liu S, Yan X, Hicks L, Lee C, Miner JN, Gillen M, Hernandez-Illas M. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with febuxostat in adults with gout: a phase IIa, open-label study. RMD Open. 2018 Apr 9;4(1):e000647. doi: 10.1136/rmdopen-2018-000647. eCollection 2018.