Lesinurad/Allopurinol 200/300 FDC Tablets Bioavailability

NCT02581553 | Completed Phase 1

• 1 other identifier: RDEA594-501
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess relative bioavailability of lesinurad/allopurinol fixed dose combination (FDC), its individual components and the effect of food.

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• 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

  Cmax is the maximum observed concentration of a drug after administration

  Days 1 and Day 8

• 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

  Tmax is the time of occurrence of cmax

  Day 1 and Day 8

• 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

  AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint

  Day 1 and Day 8

• 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

  AUC 0-∞ is a meausre of total concentration from time zero to infinity

  Day 1 and Day 8

• 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

  t1/2 is a measure of apparent terminal half-life

  Day 1 and Day 8

Secondary Outcomes (4)

• 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

Study Arms (6)

Sequence AB

EXPERIMENTAL

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

Sequence BA

EXPERIMENTAL

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

Sequence CD

EXPERIMENTAL

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

Sequence DC

EXPERIMENTAL

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

Sequence EF

EXPERIMENTAL

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

Sequence FE

EXPERIMENTAL

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

Interventions

lesinurad/allopurinol 200/300 FDC tablets DRUG

Sequence AB; Sequence BA; Sequence CD; Sequence DC

lesinurad 200 mg DRUG

Sequence AB; Sequence BA; Sequence EF; Sequence FE

allopurinol 300 mg DRUG

Sequence AB; Sequence BA

lesinurad/allopurinol 200/200 FDC tablets DRUG

Sequence EF; Sequence FE

allopurinol 200 mg DRUG

Sequence EF; Sequence FE

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body mass index ranging between 18 kg/m2 and 40 kg/m2.
• Screening serum urate level is ≤ 7.0 mg/dL.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ardea Biosciences, Inc.: lead

Study Sites (1)

Unknown Facility

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

lesinurad; Allopurinol

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• N. Bhakta

  Ardea Biosciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 21, 2015
• Study Start: October 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: August 1, 2016
• Last Updated: December 19, 2016

Record last verified: 2016-12

Locations

US (1)