RDEA3170 and Febuxostat Combination Study in Gout Subjects

Phase 2

Completed

• Conditions: Gout
• Interventions: Drug: RDEA3170 10 mg; Drug: RDEA3170 15 mg; Drug: RDEA3170 2.5; Drug: Febuxostat 40 mg; Drug: RDEA3170 5 mg; Drug: Febuxostat 80 mg

• Registration Number: NCT02246673
• Lead Sponsor: Ardea Biosciences, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-09-19
• Study First Submitted QC: 2014-09-19
• Study First Posted: 2014-09-23
• Study Start: 2014-10
• Primary Completion: 2015-07
• Study Completion: 2016-02
• Status Verified: 2017-06
• Results First Submitted: 2017-06-27
• Results First Submitted QC: 2017-06-27
• Last Update Submitted: 2017-06-27
• Results First Posted: 2017-07-27
• Last Update Posted: 2017-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RDEA3170 10 mg	Febuxostat 80 mg	Once daily (qd) with febuxostat 40mg (qd) for 7 days, and with febuxostat 80 mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 2.5 mg	Febuxostat 40 mg	Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 15 mg	Febuxostat 40 mg	Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 15 mg	Febuxostat 80 mg	Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 5 mg	Febuxostat 40 mg	Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 10 mg	RDEA3170 10 mg	Once daily (qd) with febuxostat 40mg (qd) for 7 days, and with febuxostat 80 mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 10 mg	Febuxostat 40 mg	Once daily (qd) with febuxostat 40mg (qd) for 7 days, and with febuxostat 80 mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 15 mg	RDEA3170 15 mg	Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 15 mg	RDEA3170 5 mg	Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 5 mg	Febuxostat 80 mg	Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 2.5 mg	RDEA3170 2.5	Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.
RDEA3170 2.5 mg	Febuxostat 80 mg	Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.

Primary Outcome Measures

Name	Time	Method
Serum Urate Maximum Percentage (%) Change (Emax, CB)	28 days	Maximum observed percentage (%) change from baseline in serum urate concentrations.
Urine Uric Acid % Change (0-24h) (Aeur, CB)	28 days	Percentage (%) change from baseline in the amount of uric acid recovered in urine.
Renal Clearance of Uric Acid % Change (0-24h) (CLur, CB)	28 days	Percentage (%) change from baseline in renal clearance of uric acid.
Fract. Excretion of Uric Acid % Change (0-24h) (FEUA, CB)	28 days	Percentage (%) change from baseline in fractional excretion of uric acid.

Secondary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)	Days 7 to 28	AUC 0-24 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)	Days 7 to 28	AUC last of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
Incidence of Treatment-Emergent Adverse Events	10 weeks
Maximum Observed Plasma Concentration (Cmax)	Days 7 to 28	Cmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
Time of Occurrence of Maximum Observed Concentration (Tmax)	Days 7 to 28	Tmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
Apparent Terminal Half-life (t1/2)	Days 7 to 28	t1/2 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma