Lesinurad/Allopurinol 200/300 FDC Tablets Bioequivalence

A Phase 1, Randomized, Open-Label, Replicate, Crossover Study to Assess the Bioequivalence of Lesinurad/Allopurinol Fixed-Dose Combination Tablets and Coadministered Lesinurad and Allopurinol Tablets in Fed Healthy Adult Subjects

This study will assess the bioequivalence (BE) of Lesinurad/Allopurinol Fixed-Dose Combination (FDC) Tablets and Coadministered Lesinurad and Allopurinol Tablets in Fed Healthy Adult Subjects

Study Overview

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

Detailed Description

The study will assess the BE between lesinurad/allopurinol 200/300 FDC tablets and coadministered lesinurad and allopurinol tablets in the fed state.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744

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:

• Subject has a body mass index ranging between 18 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 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 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; Day 1: lesinurad/allopurinol 200/300 FDC tablet (Sequence A) Day 8: coadministered lesinurad 200 mg + allopurinol 300 mg tablets (Sequence B) Day 15: coadministered lesinurad 200 mg + allopurinol 300 mg tablets (Sequence B) Day 22: lesinurad/allopurinol 200/300 FDC tablet (Sequence A)	Drug: lesinurad 200 mg; Drug: allopurinol 300 mg; Drug: lesinurad/allopurinol 200/300 FDC tablet
EXPERIMENTAL: Sequence BABA; Day 1: coadministered lesinurad 200 mg + allopurinol 300 mg tablets (Sequence B) Day 8: lesinurad/allopurinol 200/300 FDC tablet (Sequence A) Day 15: coadministered lesinurad 200 mg + allopurinol 300 mg tablets (Sequence B) Day 22: lesinurad/allopurinol 200/300 FDC tablet (Sequence A)	Drug: lesinurad 200 mg; Drug: allopurinol 300 mg; Drug: lesinurad/allopurinol 200/300 FDC tablet
EXPERIMENTAL: Sequence ABAB; Day 1: lesinurad/allopurinol 200/300 FDC tablet (Sequence A) Day 8: coadministered lesinurad 200 mg + allopurinol 300 mg tablets (Sequence B) Day 15: lesinurad/allopurinol 200/300 FDC tablet (Sequence A) Day 22: coadministered lesinurad 200 mg + allopurinol 300 mg tablets (Sequence B)	Drug: lesinurad 200 mg; Drug: allopurinol 300 mg; Drug: lesinurad/allopurinol 200/300 FDC tablet
EXPERIMENTAL: Sequence BAAB; Day 1: coadministered lesinurad 200 mg + allopurinol 300 mg tablets (Sequence B) Day 8: lesinurad/allopurinol 200/300 FDC tablet (Sequence A) Day 15: lesinurad/allopurinol 200/300 FDC tablet (Sequence A) Day 22: coadministered lesinurad 200 mg + allopurinol 300 mg tablets (Sequence B)	Drug: lesinurad 200 mg; Drug: allopurinol 300 mg; Drug: lesinurad/allopurinol 200/300 FDC tablet

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 coadministered monocomponent tablets	Cmax is the maximum observed concentration of a drug after administration	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 coadministered monocomponent tablets	Tmax is the time of occurrence of cmax	Days 1, 8, 15, and 22
PK endpoints in terms of area under 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 coadministered monocomponent tablets	AUC last is a measure of total plasma concentration from time zero to the last measurable concentration	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 coadministered monocomponent tablets	AUC 0-∞ is a measure of total concentration from time zero to infinity	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 coadministered monocomponent tablets	t1/2 is a measure of apparent terminal half-life	Days 1, 8, 15, 22

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events in terms of changes in laboratory parameters	8 weeks
Incidence of Adverse Events in terms of electrocardiogram parameters	8 weeks
Incidence of Adverse Events in terms of vital signs	8 weeks

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 30, 2016
• Primary Completion (ACTUAL): October 18, 2016
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: August 30, 2016
• First Submitted That Met QC Criteria: August 30, 2016
• First Posted (ESTIMATE): September 2, 2016

Study Record Updates

• Last Update Posted (ACTUAL): June 16, 2017
• Last Update Submitted That Met QC Criteria: June 15, 2017
• Last Verified: June 1, 2017

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: RDEA594-503