A PD/Safety Study of RDEA3170 in Combination With Febuxostat for Treating Gout or Asymptomatic Hyperuricemia Patients

Study Overview
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Brief Summary
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The purpose of this study is to explore the pharmacodynamics (PD), pharmacokinetics (PK), safety, and tolerability of multiple doses of RDEA3170 administered in combination with febuxostat compared to RDEA3170 administered alone and febuxostat administered alone in Japanese adult male subjects with gout or asymptomatic hyperuricemia.

Official Title
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A Phase 2a, Randomized, Open-Label, Single-Site Study to Evaluate the Pharmacodynamic Effects and Safety of RDEA3170 Administered in Combination With Febuxostat Compared to RDEA3170 Administered Alone and Febuxostat Administered Alone, Respectively in Japanese Adult Male Subjects With Gout or Asymptomatic Hyperuricemia

Conditions
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Gout and Asymptomatic Hyperuricemia

Intervention / Treatment
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* Drug: RDEA3170
* Drug: Febuxostat
* Drug: Benzbromarone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Screening serum uric acid level ≥ 8 mg/dL; Body weight ≥ 50 kg and a body mass index (BMI) ≥ 18 and ≤ 40 kg/m2; Free of any clinically significant disease or medical condition, per the Investigator's judgment. Exclusion Criteria: History or suspicion of kidney stones; Diagnosis of benign prostatic hypertrophy (BPH) or neurogenic bladder or evidence of BPH/neurogenic bladder such as thin urinary stream or difficulty in urination; An estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula; QTcF interval (QT interval corrected for heart rate using Fridericia's formula) > 450 msec at Screening; Receiving strong or moderate Cytochrome P450 (CYP) 3A inhibitors or p-glycoprotein inhibitors, or digoxin

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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: Cohort 1<br>The half of patients randomized to this cohort will be dosed in the order of Febuxostat 10mg, RDEA3170 2.5 mg + Febuxostat 10mg, RDEA3170 2.5 mg + Febuxostat 20mg, and Febuxostat 20mg. The other half will be dosed in the reverse order. | Drug: RDEA3170<br>* Oral Treatment<br>Drug: Febuxostat<br>* Oral Treatment<br>|
| Experimental: Cohort 2<br>The half of patients randomized to this cohort will be dosed in the order of Febuxostat 10mg, RDEA3170 5 mg + Febuxostat 10mg, RDEA3170 5 mg + Febuxostat 20mg, and Febuxostat 20mg. The other half will be dosed in the reverse order. | Drug: RDEA3170<br>* Oral Treatment<br>Drug: Febuxostat<br>* Oral Treatment<br>|
| Experimental: Cohort 3<br>The half of patients randomized to this cohort will be dosed in the order of Febuxostat 20mg, RDEA3170 5 mg + Febuxostat 20mg, RDEA3170 5 mg + Febuxostat 40mg, and Febuxostat 40mg. The other half will be dosed in the reverse order. | Drug: RDEA3170<br>* Oral Treatment<br>Drug: Febuxostat<br>* Oral Treatment<br>|
| Experimental: Cohort 4<br>The half of patients randomized to this cohort will be dosed in the order of Febuxostat 20mg, RDEA3170 10 mg + Febuxostat 20mg, RDEA3170 10 mg + Febuxostat 40mg, and Febuxostat 40mg. The other half will be dosed in the reverse order. | Drug: RDEA3170<br>* Oral Treatment<br>Drug: Febuxostat<br>* Oral Treatment<br>|
| Experimental: Cohort 5<br>RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg | Drug: RDEA3170<br>* Oral Treatment<br>|
| Experimental: Cohort 6<br>The half of patients randomized to this cohort will be dosed in the order of Benzbromarone 50 mg, Febuxostat 10mg+RDEA3170 2.5 mg, then Febuxostat 20mg+RDEA3170 5 mg. The other half will be dosed in the order of Febuxostat 10mg+RDEA3170 2.5 mg, Febuxostat 20mg+RDEA3170 5 mg, then Benzbromarone 50mg. | Drug: RDEA3170<br>* Oral Treatment<br>Drug: Febuxostat<br>* Oral Treatment<br>Drug: Benzbromarone<br>* Oral Treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum uric acid level | % change per treatment will be compared. | baseline and day 7 on each treatment | 
| Change in Urinary excretion of uric acid | Timed urinary uric acid excretion per treatment will be compared | baseline and day 7 on each treatment | 
| Renal clearance of uric acid | Renal clearance of uric acid will be calculated. | baseline and day 7 on each treatment | 
| Fractional excretion of uric acid | Fractional excretion and renal clearance of uric acid will be calculated. | baseline and day 7 on each treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment. | 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment | 
| Time to reach maximum concentration (tmax) | To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment. | 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment | 
| Area under the concentration-time curve (AUC) | To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment. | 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment | 
| Half life (t1/2) | To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment. | 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment | 
| Incidence of adverse events | To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170 | Day 1 and Day 7 on each treatment | 
| Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters | To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170 | Day 1 and Day 8 on each treatment | 
| Changes in vital signs and physical examination findings | To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170 | Day 1 and Day 8 on each treatment | 
| Incidence of adverse events | To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170 | Day 42 of the study as follow up | 
| Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters | To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170 | Day 42 of the study as follow up | 
| Changes in vital signs and physical examination findings | To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170 | Day 42 of the study as follow up |