A PD/Safety Study of RDEA3170 in Combination With Febuxostat for Treating Gout or Asymptomatic Hyperuricemia Patients

Overview

The purpose of this study is to explore the pharmacodynamics (PD), pharmacokinetics (PK), safety, and tolerability of multiple doses of RDEA3170 administered in combination with febuxostat compared to RDEA3170 administered alone and febuxostat administered alone in Japanese adult male subjects with gout or asymptomatic hyperuricemia.

Full Title of Study: “A Phase 2a, Randomized, Open-Label, Single-Site Study to Evaluate the Pharmacodynamic Effects and Safety of RDEA3170 Administered in Combination With Febuxostat Compared to RDEA3170 Administered Alone and Febuxostat Administered Alone, Respectively in Japanese Adult Male Subjects With Gout or Asymptomatic Hyperuricemia”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2015

Interventions

  • Drug: RDEA3170
    • Oral Treatment
  • Drug: Febuxostat
    • Oral Treatment
  • Drug: Benzbromarone
    • Oral Treatment

Arms, Groups and Cohorts

  • Experimental: Cohort 1
    • The half of patients randomized to this cohort will be dosed in the order of Febuxostat 10mg, RDEA3170 2.5 mg + Febuxostat 10mg, RDEA3170 2.5 mg + Febuxostat 20mg, and Febuxostat 20mg. The other half will be dosed in the reverse order.
  • Experimental: Cohort 2
    • The half of patients randomized to this cohort will be dosed in the order of Febuxostat 10mg, RDEA3170 5 mg + Febuxostat 10mg, RDEA3170 5 mg + Febuxostat 20mg, and Febuxostat 20mg. The other half will be dosed in the reverse order.
  • Experimental: Cohort 3
    • The half of patients randomized to this cohort will be dosed in the order of Febuxostat 20mg, RDEA3170 5 mg + Febuxostat 20mg, RDEA3170 5 mg + Febuxostat 40mg, and Febuxostat 40mg. The other half will be dosed in the reverse order.
  • Experimental: Cohort 4
    • The half of patients randomized to this cohort will be dosed in the order of Febuxostat 20mg, RDEA3170 10 mg + Febuxostat 20mg, RDEA3170 10 mg + Febuxostat 40mg, and Febuxostat 40mg. The other half will be dosed in the reverse order.
  • Experimental: Cohort 5
    • RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg
  • Experimental: Cohort 6
    • The half of patients randomized to this cohort will be dosed in the order of Benzbromarone 50 mg, Febuxostat 10mg+RDEA3170 2.5 mg, then Febuxostat 20mg+RDEA3170 5 mg. The other half will be dosed in the order of Febuxostat 10mg+RDEA3170 2.5 mg, Febuxostat 20mg+RDEA3170 5 mg, then Benzbromarone 50mg.

Clinical Trial Outcome Measures

Primary Measures

  • Change in Serum uric acid level
    • Time Frame: baseline and day 7 on each treatment
    • % change per treatment will be compared.
  • Change in Urinary excretion of uric acid
    • Time Frame: baseline and day 7 on each treatment
    • Timed urinary uric acid excretion per treatment will be compared
  • Renal clearance of uric acid
    • Time Frame: baseline and day 7 on each treatment
    • Renal clearance of uric acid will be calculated.
  • Fractional excretion of uric acid
    • Time Frame: baseline and day 7 on each treatment
    • Fractional excretion and renal clearance of uric acid will be calculated.

Secondary Measures

  • Maximum plasma concentration (Cmax)
    • Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post‐dose on each treatment
    • To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
  • Time to reach maximum concentration (tmax)
    • Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post‐dose on each treatment
    • To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
  • Area under the concentration-time curve (AUC)
    • Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post‐dose on each treatment
    • To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
  • Half life (t1/2)
    • Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post‐dose on each treatment
    • To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
  • Incidence of adverse events
    • Time Frame: Day 1 and Day 7 on each treatment
    • To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
  • Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
    • Time Frame: Day 1 and Day 8 on each treatment
    • To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
  • Changes in vital signs and physical examination findings
    • Time Frame: Day 1 and Day 8 on each treatment
    • To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
  • Incidence of adverse events
    • Time Frame: Day 42 of the study as follow up
    • To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
  • Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
    • Time Frame: Day 42 of the study as follow up
    • To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
  • Changes in vital signs and physical examination findings
    • Time Frame: Day 42 of the study as follow up
    • To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170

Participating in This Clinical Trial

Inclusion Criteria

  • Screening serum uric acid level ≥ 8 mg/dL;
  • Body weight ≥ 50 kg and a body mass index (BMI) ≥ 18 and ≤ 40 kg/m2;
  • Free of any clinically significant disease or medical condition, per the Investigator's judgment.

Exclusion Criteria

  • History or suspicion of kidney stones;
  • Diagnosis of benign prostatic hypertrophy (BPH) or neurogenic bladder or evidence of BPH/neurogenic bladder such as thin urinary stream or difficulty in urination;
  • An estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula;
  • QTcF interval (QT interval corrected for heart rate using Fridericia's formula) > 450 msec at Screening;
  • Receiving strong or moderate Cytochrome P450 (CYP) 3A inhibitors or p-glycoprotein inhibitors, or digoxin

Gender Eligibility: Male

Minimum Age: 20 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • AstraZeneca
  • Collaborator
    • Ardea Biosciences, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor

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