Lesinurad/Allopurinol 200/300 FDC Tablets Bioavailability

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Actual): 116
• 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: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence AB; 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
Experimental: Sequence BA; 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
Experimental: Sequence CD; 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
Experimental: Sequence DC; 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
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)	Drug: lesinurad 200 mg; Drug: lesinurad/allopurinol 200/200 FDC tablets; Drug: allopurinol 200 mg
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).	Drug: lesinurad 200 mg; Drug: lesinurad/allopurinol 200/200 FDC tablets; Drug: allopurinol 200 mg

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 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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: October 12, 2015
• First Submitted That Met QC Criteria: October 19, 2015
• First Posted (Estimate): October 21, 2015

Study Record Updates

• Last Update Posted (Estimate): December 19, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: December 1, 2016

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: RDEA594-501