Lesinurad/Allopurinol 200/300 FDC Tablets Bioavailability
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Drug: lesinurad/allopurinol 200/300 FDC tabletsDrug: lesinurad/allopurinol 200/200 FDC tablets
- Registration Number
- NCT02581553
- Lead Sponsor
- Ardea Biosciences, Inc.
- Brief Summary
This study will assess relative bioavailability of lesinurad/allopurinol fixed dose combination (FDC), its individual components and the effect of food.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 116
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Sequence AB lesinurad/allopurinol 200/300 FDC tablets Day 1: lesinurad/allopurinol FDC tablets (Treatment A); Day 8: lesinurad + allopurinol (Treatment B) Sequence AB lesinurad 200 mg Day 1: lesinurad/allopurinol FDC tablets (Treatment A); Day 8: lesinurad + allopurinol (Treatment B) Sequence AB allopurinol 300 mg Day 1: lesinurad/allopurinol FDC tablets (Treatment A); Day 8: lesinurad + allopurinol (Treatment B) Sequence BA lesinurad/allopurinol 200/300 FDC tablets Day 1: lesinurad + allopurinol (Treatment B); Day 8: lesinurad/allopurinol FDC tablets (Treatment A). Sequence BA lesinurad 200 mg Day 1: lesinurad + allopurinol (Treatment B); Day 8: lesinurad/allopurinol FDC tablets (Treatment A). Sequence CD lesinurad/allopurinol 200/300 FDC tablets Day 1: lesinurad/allopurinol FDC tablets (Treatment C \[fasted\]); Day 8: lesinurad/allopurinol FDC tablets (Treatment D \[fed\]). Sequence DC lesinurad/allopurinol 200/300 FDC tablets Day 1: lesinurad/allopurinol FDC tablets (Treatment D \[fed\]); Day 8: lesinurad/allopurinol FDC tablets (Treatment C \[fasted\]). Sequence EF lesinurad 200 mg Day 1: lesinurad/allopurinol 200/200 FDC tablets (Treatment E); Day 8: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) Sequence FE lesinurad/allopurinol 200/200 FDC tablets Day 1: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) (Treatment F); Day 8: lesinurad/allopurinol 200/200 FDC tablets (Treatment E). Sequence EF lesinurad/allopurinol 200/200 FDC tablets Day 1: lesinurad/allopurinol 200/200 FDC tablets (Treatment E); Day 8: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) Sequence FE lesinurad 200 mg Day 1: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) (Treatment F); Day 8: lesinurad/allopurinol 200/200 FDC tablets (Treatment E). Sequence FE allopurinol 200 mg Day 1: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) (Treatment F); Day 8: lesinurad/allopurinol 200/200 FDC tablets (Treatment E). Sequence BA allopurinol 300 mg Day 1: lesinurad + allopurinol (Treatment B); Day 8: lesinurad/allopurinol FDC tablets (Treatment A). Sequence EF allopurinol 200 mg Day 1: lesinurad/allopurinol 200/200 FDC tablets (Treatment E); Day 8: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2)
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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