Phase 2a RDEA3170 and Allopurinol 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 of RDEA3170 administered in combination with allopurinol compared with allopurinol 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 Allopurinol Compared With Allopurinol Administered Alone in Adult Subjects With Gout

Conditions
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Gout

Intervention / Treatment
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* Drug: RDEA3170 2.5 mg
* Drug: allopurinol 300 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is able to understand the study procedures and the risks involved and is willing to provide written informed consent before the first study-related activity. Subject 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. Subject has a body weight ≥ 50 kg (110 lbs.) and a body mass index ≥ 18 and ≤ 45 kg/m2. Subject has a Screening serum urate level ≥ 8 mg/dL. Subject is free of any clinically significant disease or medical condition, per the Investigator's judgment. Exclusion Criteria: Subject is unable to take colchicine for gout flare prophylaxis. Subject has a history or suspicion of kidney stones. Subject has any gastrointestinal disorder that affects motility and/or absorption. Subject had 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. Subject has Screening laboratory parameters that are outside the normal limits and are considered clinically significant by the Investigator. Subject has an estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight during the Screening period. Subject is 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. Subject is 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 2.5 mg, 7.5 mg and 15 mg<br>RDEA3170 2.5 mg, 7.5 mg and 15 mg once daily (qd) in combination with allopurinol 300 mg (qd and twice daily (bid)) | Drug: RDEA3170 2.5 mg<br>* Cohort 1: RDEA3170 2.5 mg, 7.5 mg (2.5 mg × 3 tablets), and 15 mg (2.5 mg × 6 tablets). Cohort 2: RDEA3170 5 mg (2.5 mg × 2 tablets), 10 mg (2.5 mg × 4 tablets), and 20 mg (2.5 mg × 8 tablets).<br>Drug: allopurinol 300 mg<br>* allopurinol 300 mg, allopurinol 600 mg (300 mg x 2 tablets)<br>|
| Experimental: RDEA3170 5 mg, 10 mg and 20 mg<br>RDEA3170 5 mg, 10 mg 20 mg qd in combination with allopurinol 300 mg (qd and bid) | Drug: RDEA3170 2.5 mg<br>* Cohort 1: RDEA3170 2.5 mg, 7.5 mg (2.5 mg × 3 tablets), and 15 mg (2.5 mg × 6 tablets). Cohort 2: RDEA3170 5 mg (2.5 mg × 2 tablets), 10 mg (2.5 mg × 4 tablets), and 20 mg (2.5 mg × 8 tablets).<br>Drug: allopurinol 300 mg<br>* allopurinol 300 mg, allopurinol 600 mg (300 mg x 2 tablets)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) | 
| Cohort 1 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol. | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) | 
| Cohort 1 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) | 
| Cohort 1 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) | 
| Cohort 2 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) | 
| Cohort 2 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol. | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) | 
| Cohort 2 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) | 
| Cohort 2 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) | Cmax of Allopurinol alone or in combination with RDEA3170 | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) | 
| Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax of Allopurinol alone or in combination with RDEA3170 | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) | 
| Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of Allopurinol alone or in combination with RDEA3170 | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) | 
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of Allopurinol alone or in combination with RDEA3170 | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) | 
| Apparent Terminal Half-life (t1/2) | t1/2 of Allopurinol alone or in combination with RDEA3170 | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) | 
| Number of Participants With Treatment-Emergent Adverse Events |  | 11 weeks |