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

NCT03272425 | Completed Phase 1

• 1 other identifier: RDEA594-504
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gout

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 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 Outcomes (4)

• 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

Study Arms (4)

Sequence ABBA

EXPERIMENTAL

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; Drug: lesinurad 200 mg; Drug: allopurinol 300 mg

Sequence BABA

EXPERIMENTAL

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; Drug: lesinurad 200 mg; Drug: allopurinol 300 mg

Sequence ABAB

EXPERIMENTAL

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; Drug: lesinurad 200 mg; Drug: allopurinol 300 mg

Sequence BAAB

EXPERIMENTAL

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; Drug: lesinurad 200 mg; Drug: allopurinol 300 mg

Interventions

lesinurad/allopurinol 200/300 FDC tablets DRUG

Test Drug

Sequence ABAB; Sequence ABBA; Sequence BAAB; Sequence BABA

lesinurad 200 mg DRUG

Comparator 1

Sequence ABAB; Sequence ABBA; Sequence BAAB; Sequence BABA

allopurinol 300 mg DRUG

Comparator 2

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:

• Body mass index ranging between 18.5 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 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.

Sponsors & Collaborators

• Ardea Biosciences, Inc.: lead

Study Sites (1)

CAEP - Centro Avançado de Estudos e Pesquisas Ltda.

Campinas, São Paulo, Brazil

Location

MeSH Terms

Conditions

Gout

Interventions

lesinurad; Allopurinol

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

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: September 1, 2017
• First Posted: September 5, 2017
• Study Start: August 14, 2017
• Primary Completion: October 4, 2017
• Study Completion: October 4, 2017
• Last Updated: November 7, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)