Lesinurad/Allopurinol 200/300 FDC Tablets Bioavailability
Study Details
Study Description
Brief Summary
This study will assess relative bioavailability of lesinurad/allopurinol fixed dose combination (FDC), its individual components and the effect of food.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The study comprises 2 parts. Part 1 will assess the relative BA of lesinurad/allopurinol FDC and monocomponents in fasted subjects. Part 2 will assess the effect of food on the PK of FDC tablets.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sequence AB Day 1: lesinurad/allopurinol FDC tablets (Treatment A); Day 8: lesinurad + allopurinol (Treatment B) |
Drug: lesinurad/allopurinol 200/300 FDC tablets
Drug: lesinurad 200 mg
Drug: allopurinol 300 mg
|
| Experimental: Sequence BA Day 1: lesinurad + allopurinol (Treatment B); Day 8: lesinurad/allopurinol FDC tablets (Treatment A). |
Drug: lesinurad/allopurinol 200/300 FDC tablets
Drug: lesinurad 200 mg
Drug: allopurinol 300 mg
|
| Experimental: Sequence CD Day 1: lesinurad/allopurinol FDC tablets (Treatment C [fasted]); Day 8: lesinurad/allopurinol FDC tablets (Treatment D [fed]). |
Drug: lesinurad/allopurinol 200/300 FDC tablets
|
| Experimental: Sequence DC Day 1: lesinurad/allopurinol FDC tablets (Treatment D [fed]); Day 8: lesinurad/allopurinol FDC tablets (Treatment C [fasted]). |
Drug: lesinurad/allopurinol 200/300 FDC tablets
|
| Experimental: Sequence EF Day 1: lesinurad/allopurinol 200/200 FDC tablets (Treatment E); Day 8: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) |
Drug: lesinurad 200 mg
Drug: lesinurad/allopurinol 200/200 FDC tablets
Drug: allopurinol 200 mg
|
| Experimental: Sequence FE Day 1: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) (Treatment F); Day 8: lesinurad/allopurinol 200/200 FDC tablets (Treatment E). |
Drug: lesinurad 200 mg
Drug: lesinurad/allopurinol 200/200 FDC tablets
Drug: allopurinol 200 mg
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetics (PK) endpoints in terms of maximum observed concentration (Cmax) for lesinurad/allopurinol 200/300 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets [Days 1 and Day 8]
Cmax is the maximum observed concentration of a drug after administration
- PK endpoints in terms of time of occurrence of maximum observed concentration (tmax) for lesinurad/allopurinol 200/300 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets [Day 1 and Day 8]
Tmax is the time of occurrence of cmax
- 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 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets [Day 1 and Day 8]
AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint
- 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 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets [Day 1 and Day 8]
AUC 0-∞ is a meausre of total concentration from time zero to infinity
- PK endpoints in terms of apparent terminal half-life (t1/2) for lesinurad/allopurinol 200/300 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets [Day 1 and Day 8]
t1/2 is a measure of apparent terminal half-life
Secondary Outcome Measures
- Incidence of Adverse Events in terms of changes in laboratory parameters [6 weeks]
- Incidence of Adverse Events in terms of electrocardiogram parameters [6 weeks]
- Incidence of Adverse Events in terms of vital signs [6 weeks]
- Incidence of Adverse Events in terms of physical examination findings [6 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Body mass index ranging between 18 kg/m2 and 40 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 suspicion of kidney stones.
-
Estimated creatinine clearance, as determined at Screening, of < 90 mL/min calculated by the Cockcroft-Gault formula using ideal body weight.
-
Undergone major surgery within 3 months prior to Screening.
-
Donated blood or experienced significant blood loss (> 450 mL) within 12 weeks prior to Day 1or 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Austin | Texas | United States | 78744 |
Sponsors and Collaborators
- Ardea Biosciences, Inc.
Investigators
- Study Director: N. Bhakta, Ardea Biosciences, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RDEA594-501