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

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.

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.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Drug: lesinurad/allopurinol 200/300 FDC tablets; Drug: lesinurad 200 mg; Drug: allopurinol 300 mg

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil
      • CAEP - Centro Avancado de Estudos e Pesquisas Ltda.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	Drug: lesinurad/allopurinol 200/300 FDC tablets; Test Drug; Drug: lesinurad 200 mg; Comparator 1; Drug: allopurinol 300 mg; 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).	Drug: lesinurad/allopurinol 200/300 FDC tablets; Test Drug; Drug: lesinurad 200 mg; Comparator 1; Drug: allopurinol 300 mg; 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).	Drug: lesinurad/allopurinol 200/300 FDC tablets; Test Drug; Drug: lesinurad 200 mg; Comparator 1; Drug: allopurinol 300 mg; 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).	Drug: lesinurad/allopurinol 200/300 FDC tablets; Test Drug; Drug: lesinurad 200 mg; Comparator 1; Drug: allopurinol 300 mg; Comparator 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) endpoints in terms of maximum observed concentration (Cmax) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets	Cmax is the maximum observed concentration of a drug after administration	Days 1, 8, 15 and 22
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	AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint	Days 1, 8, 15 and 22
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	AUC 0-∞ is a meausre of total concentration from time zero to infinity	Days 1, 8, 15 and 22
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	Tmax is the time of occurrence of cmax	Days 1, 8, 15 and 22
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	t1/2 is a measure of apparent terminal half-life	Days 1, 8, 15 and 22

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events in terms of changes in laboratory parameters	26 days
Incidence of Adverse Events in terms of electrocardiogram parameters	26 days
Incidence of Adverse Events in terms of vital signs	26 days
Incidence of Adverse Events in terms of physical examination findings	26 days

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 14, 2017
• Primary Completion (ACTUAL): October 4, 2017
• Study Completion (ACTUAL): October 4, 2017

Study Registration Dates

• First Submitted: September 1, 2017
• First Submitted That Met QC Criteria: September 1, 2017
• First Posted (ACTUAL): September 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 7, 2018
• Last Update Submitted That Met QC Criteria: November 6, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Renal Agents; Uricosuric Agents; Allopurinol; Lesinurad
• Other Study ID Numbers: RDEA594-504

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No