Lesinurad/Allopurinol 200/300 FDC Tablets Bioequivalence

NCT02888054 | Completed Phase 1

• 1 other identifier: RDEA594-503
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (3)

• 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

Study Arms (4)

Sequence ABBA

EXPERIMENTAL

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/allopurinol 200/300 FDC tablet; Drug: lesinurad 200 mg; Drug: allopurinol 300 mg

Sequence BABA

EXPERIMENTAL

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/allopurinol 200/300 FDC tablet; Drug: lesinurad 200 mg; Drug: allopurinol 300 mg

Sequence ABAB

EXPERIMENTAL

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/allopurinol 200/300 FDC tablet; Drug: lesinurad 200 mg; Drug: allopurinol 300 mg

Sequence BAAB

EXPERIMENTAL

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/allopurinol 200/300 FDC tablet; Drug: lesinurad 200 mg; Drug: allopurinol 300 mg

Interventions

lesinurad/allopurinol 200/300 FDC tablet DRUG

Sequence ABAB; Sequence ABBA; Sequence BAAB; Sequence BABA

lesinurad 200 mg DRUG

Sequence ABAB; Sequence ABBA; Sequence BAAB; Sequence BABA

allopurinol 300 mg DRUG

Sequence ABAB; Sequence ABBA; Sequence BAAB; Sequence BABA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has a body mass index ranging between 18 kg/m2 and 30 kg/m2.
• Screening serum urate level is ≤ 7.0 mg/dL.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ardea Biosciences, Inc.: lead

Study Sites (1)

Unknown Facility

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

lesinurad; Allopurinol

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• N. Bhakta

  Ardea Biosciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2016
• First Posted: September 2, 2016
• Study Start: August 30, 2016
• Primary Completion: October 18, 2016
• Study Completion: February 1, 2017
• Last Updated: June 16, 2017

Record last verified: 2017-06

Locations

US (1)