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

Overview

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.

Full Title of Study: “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.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 4, 2017

Interventions

  • Drug: lesinurad/allopurinol 200/300 FDC tablets
    • Test Drug
  • Drug: lesinurad 200 mg
    • Comparator 1
  • Drug: allopurinol 300 mg
    • Comparator 2

Arms, Groups and Cohorts

  • Experimental: Sequence ABBA
    • 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).
  • Experimental: Sequence BABA
    • 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).
  • Experimental: Sequence ABAB
    • 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).
  • Experimental: Sequence BAAB
    • 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).

Clinical Trial Outcome Measures

Primary Measures

  • Pharmacokinetics (PK) endpoints in terms of maximum observed concentration (Cmax) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
    • Time Frame: Days 1, 8, 15 and 22
    • Cmax is the maximum observed concentration of a drug after administration
  • 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
    • Time Frame: Days 1, 8, 15 and 22
    • 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 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
    • Time Frame: Days 1, 8, 15 and 22
    • AUC 0-∞ is a meausre of total concentration from time zero to infinity
  • 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
    • Time Frame: Days 1, 8, 15 and 22
    • Tmax is the time of occurrence of cmax
  • 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
    • Time Frame: Days 1, 8, 15 and 22
    • 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: 26 days
  • Incidence of Adverse Events in terms of electrocardiogram parameters
    • Time Frame: 26 days
  • Incidence of Adverse Events in terms of vital signs
    • Time Frame: 26 days
  • Incidence of Adverse Events in terms of physical examination findings
    • Time Frame: 26 days

Participating in This Clinical Trial

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.

Gender Eligibility: All

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.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.