RDEA3170 and Allopurinol Combination Study in Gout Subjects

Study Overview
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Brief Summary
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This is a Phase 1b, randomized, open-label, drug-drug interaction study in adult male subjects with gout. It is designed to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of RDEA3170 or allopurinol alone and in combination in the fed state.

Official Title
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A Phase 1b, Randomized, Open-label Study to Evaluate the Potential Pharmacokinetic and Pharmacodynamic Interactions Between RDEA3170 and Allopurinol in Adult Male Subjects With Gout

Conditions
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Gout

Intervention / Treatment
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* Drug: RDEA3170 10 mg
* Drug: allopurinol 300 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 and ≤ 10 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 an estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight at Screening prior to Day -2. Subject is on unstable doses of chronic medications. Subjects taking medications for chronic medical conditions must be on stable doses during the course of the study, including the Screening period. Dose adjustments are allowed if deemed medically necessary by the investigator and following discussion with the medical monitor Chronic and stable doses of losartan, fenofibrate, guaifenesin, and sodium-glucose linked transporter-2 inhibitors are permitted if the dose is 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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Male

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence A<br>RDEA3170 qd (once daily), RDEA3170 + allopurinol qd, allopurinol qd | Drug: RDEA3170 10 mg<br> <br> Drug: allopurinol 300 mg<br> <br> |
| Experimental: Sequence B<br>allopurinol qd, RDEA3170 + allopurinol qd, RDEA3170 qd | Drug: RDEA3170 10 mg<br> <br> Drug: allopurinol 300 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Cmax of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | 22 days | 
| Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination | 22 days | 
| Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | 22 days | 
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | 22 days | 
| Apparent Terminal Half-life (t1/2) | t1/2 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination | 22 days | 
| Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) | Ae0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | 22 days | 
| Renal Clearance of the Drug From Time Zero up to 24 Hours Postdose (CRL0-24) | CLR0-24 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination | 22 days | 
| Pharmacodynamics (PD) Profile of Uric Acid From Serum and Urine |  | 22 days | 
| Maximum Observed Plasma Concentration (Cmax) | Cmax of RDEA3170 Alone and In Combination with Allopurinol | 22 days | 
| Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of RDEA3170 Alone and In Combination with Allopurinol | 22 days | 
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of RDEA3170 Alone and In Combination with Allopurinol | 22 days | 
| Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) | Ae0-24 of RDEA3170 Alone and In Combination with Allopurinol | 22 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events |  | 22 days |