RDEA3170 and Febuxostat Combination Study in Gout Subjects

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gout

Intervention / Treatment
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* Drug: RDEA3170 15 mg
* Drug: RDEA3170 10 mg
* Drug: RDEA3170 2.5
* Drug: RDEA3170 5 mg
* Drug: Febuxostat 40 mg
* Drug: Febuxostat 80 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RDEA3170 10 mg<br>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. | Drug: RDEA3170 10 mg<br> <br> Drug: Febuxostat 40 mg<br> <br> Drug: Febuxostat 80 mg<br> <br> |
| Experimental: RDEA3170 15 mg<br>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. | Drug: RDEA3170 15 mg<br> <br> Drug: RDEA3170 5 mg<br> <br> Drug: Febuxostat 40 mg<br> <br> Drug: Febuxostat 80 mg<br> <br> |
| Experimental: RDEA3170 5 mg<br>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. | Drug: Febuxostat 40 mg<br> <br> Drug: Febuxostat 80 mg<br> <br> |
| Experimental: RDEA3170 2.5 mg<br>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. | Drug: RDEA3170 2.5<br> <br> Drug: Febuxostat 40 mg<br> <br> Drug: Febuxostat 80 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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