Lesinurad/Allopurinol 200/300 Fixed-Dose Combination (FDC) Tablets Bioequivalence.

Study Overview
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Brief Summary
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To assess the bioequivalence between lesinurad/allopurinol 200/300 FDC tablets and coadministered lesinurad and allopurinol tablets in the fasted state based on the pharmacokinetic (PK) evaluation of lesinurad and allopurinol in healthy adult subjects.

Official Title
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A Randomized, Open-label, Replicate, Crossover, 4-period Study to Assess the Bioequivalence of Lesinurad/Allopurinol Fixed-dose Combination 200/300 mg Tablets From Ardea Biosciences, Inc. (Test Drug) Versus Lesinurad, 200 mg Tablet From AstraZeneca (Comparator 1) Coadministered With Zyloric®, Allopurinol 300 mg Tablet From Aspen Pharma Industria Farmaceutica Ltda. (Comparator 2) in Healthy Female and Male Adult Subjects, Under Fasting Conditions.

Conditions
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Gout

Intervention / Treatment
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* Drug: lesinurad/allopurinol 200/300 FDC tablets
* Drug: lesinurad 200 mg
* Drug: allopurinol 300 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index ranging between 18.5 kg/m2 and 30 kg/m2. Screening serum urate level is ≤ 7.0 mg/dL. Exclusion Criteria: Asian subject who has a positive test for the HLA-B*5801 allele. History or current diagnosis of kidney stones. Estimated creatinine clearance, as determined at Screening, of ≤ 80 mL/min calculated by the Cockcroft-Gault formula using ideal body weight. Undergone major surgery within 3 months prior to Screening. Donated blood within 4 weeks prior to Day 1 or experienced an event (other than blood donation) of significant blood loss (> 450 mL) within 12 weeks prior to Day 1 or has given a plasma donation within 4 weeks prior to Day 1. Inadequate venous access or unsuitable veins for repeated venipuncture. Received any strong or moderate enzyme-inducing drug or product within 2 months prior to Screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence ABBA<br>Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2). | Drug: lesinurad/allopurinol 200/300 FDC tablets<br>* Test Drug<br>Drug: lesinurad 200 mg<br>* Comparator 1<br>Drug: allopurinol 300 mg<br>* Comparator 2<br>|
| Experimental: Sequence BABA<br>Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2). | Drug: lesinurad/allopurinol 200/300 FDC tablets<br>* Test Drug<br>Drug: lesinurad 200 mg<br>* Comparator 1<br>Drug: allopurinol 300 mg<br>* Comparator 2<br>|
| Experimental: Sequence ABAB<br>Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2). | Drug: lesinurad/allopurinol 200/300 FDC tablets<br>* Test Drug<br>Drug: lesinurad 200 mg<br>* Comparator 1<br>Drug: allopurinol 300 mg<br>* Comparator 2<br>|
| Experimental: Sequence BAAB<br>Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2). | Drug: lesinurad/allopurinol 200/300 FDC tablets<br>* Test Drug<br>Drug: lesinurad 200 mg<br>* Comparator 1<br>Drug: allopurinol 300 mg<br>* Comparator 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) endpoints in terms of maximum observed concentration (Cmax) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets | Cmax is the maximum observed concentration of a drug after administration | Days 1, 8, 15 and 22 | 
| PK endpoints in terms of area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint (AUC last) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets | AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint | Days 1, 8, 15 and 22 | 
| PK endpoints in terms of area under the plasma concentration time curve from and from zero to infinity (AUC 0-∞) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets | AUC 0-∞ is a meausre of total concentration from time zero to infinity | Days 1, 8, 15 and 22 | 
| PK endpoints in terms of time of occurrence of maximum observed concentration (tmax) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets | Tmax is the time of occurrence of cmax | Days 1, 8, 15 and 22 | 
| PK endpoints in terms of apparent terminal half-life (t1/2) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets | t1/2 is a measure of apparent terminal half-life | Days 1, 8, 15 and 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events in terms of changes in laboratory parameters |  | 26 days | 
| Incidence of Adverse Events in terms of electrocardiogram parameters |  | 26 days | 
| Incidence of Adverse Events in terms of vital signs |  | 26 days | 
| Incidence of Adverse Events in terms of physical examination findings |  | 26 days |