Lesinurad/Allopurinol 200/300 FDC Tablets Bioavailability

Overview

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

Full Title of Study: “A Phase 1, Randomized, Open-Label, Crossover Study to Assess the Relative Bioavailability of Lesinurad/Allopurinol Fixed Dose Combination Tablets and Coadministered Lesinurad and Allopurinol Tablets and the Effect of Food on the Pharmacokinetics of Lesinurad/Allopurinol Fixed Dose Combination Tablets in Healthy Adult Male Subjects”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 2016

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.

Interventions

  • Drug: lesinurad/allopurinol 200/300 FDC tablets
  • Drug: lesinurad 200 mg
  • Drug: allopurinol 300 mg
  • Drug: lesinurad/allopurinol 200/200 FDC tablets
  • Drug: allopurinol 200 mg

Arms, Groups and Cohorts

  • Experimental: Sequence AB
    • Day 1: lesinurad/allopurinol FDC tablets (Treatment A); Day 8: lesinurad + allopurinol (Treatment B)
  • Experimental: Sequence BA
    • Day 1: lesinurad + allopurinol (Treatment B); Day 8: lesinurad/allopurinol FDC tablets (Treatment A).
  • Experimental: Sequence CD
    • Day 1: lesinurad/allopurinol FDC tablets (Treatment C [fasted]); Day 8: lesinurad/allopurinol FDC tablets (Treatment D [fed]).
  • Experimental: Sequence DC
    • Day 1: lesinurad/allopurinol FDC tablets (Treatment D [fed]); Day 8: lesinurad/allopurinol FDC tablets (Treatment C [fasted]).
  • 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)
  • 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).

Clinical Trial Outcome Measures

Primary 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: Day 1 and Day 8
    • t1/2 is a measure of apparent terminal half-life

Secondary Measures

  • Incidence of Adverse Events in terms of changes in laboratory parameters
    • Time Frame: 6 weeks
  • Incidence of Adverse Events in terms of electrocardiogram parameters
    • Time Frame: 6 weeks
  • Incidence of Adverse Events in terms of vital signs
    • Time Frame: 6 weeks
  • Incidence of Adverse Events in terms of physical examination findings
    • Time Frame: 6 weeks

Participating in This Clinical Trial

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.
  • Gender Eligibility: Male

    Minimum Age: 18 Years

    Maximum Age: 65 Years

    Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

    Investigator Details

    • Lead Sponsor
      • Ardea Biosciences, Inc.
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • N. Bhakta, Study Director, Ardea Biosciences, Inc.

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