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

Primary Purpose

Gout and Asymptomatic Hyperuricemia

Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
RDEA3170
Febuxostat
Benzbromarone
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Gout and Asymptomatic Hyperuricemia

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Cohort 6

Arm Description

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.

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.

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.

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.

RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg

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.

Outcomes

Primary Outcome Measures

Change in Serum uric acid level
% change per treatment will be compared.
Change in Urinary excretion of uric acid
Timed urinary uric acid excretion per treatment will be compared
Renal clearance of uric acid
Renal clearance of uric acid will be calculated.
Fractional excretion of uric acid
Fractional excretion and renal clearance of uric acid will be calculated.

Secondary Outcome Measures

Maximum plasma concentration (Cmax)
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Time to reach maximum concentration (tmax)
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Area under the concentration-time curve (AUC)
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Half life (t1/2)
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Incidence of adverse events
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
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
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
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
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
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170

Full Information

First Posted
December 9, 2014
Last Updated
June 11, 2015
Sponsor
AstraZeneca
Collaborators
Ardea Biosciences, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02317861
Brief Title
A PD/Safety Study of RDEA3170 in Combination With Febuxostat for Treating Gout or Asymptomatic Hyperuricemia Patients
Official Title
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
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Ardea Biosciences, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gout and Asymptomatic Hyperuricemia

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg
Arm Title
Cohort 6
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
RDEA3170
Intervention Description
Oral Treatment
Intervention Type
Drug
Intervention Name(s)
Febuxostat
Intervention Description
Oral Treatment
Intervention Type
Drug
Intervention Name(s)
Benzbromarone
Intervention Description
Oral Treatment
Primary Outcome Measure Information:
Title
Change in Serum uric acid level
Description
% change per treatment will be compared.
Time Frame
baseline and day 7 on each treatment
Title
Change in Urinary excretion of uric acid
Description
Timed urinary uric acid excretion per treatment will be compared
Time Frame
baseline and day 7 on each treatment
Title
Renal clearance of uric acid
Description
Renal clearance of uric acid will be calculated.
Time Frame
baseline and day 7 on each treatment
Title
Fractional excretion of uric acid
Description
Fractional excretion and renal clearance of uric acid will be calculated.
Time Frame
baseline and day 7 on each treatment
Secondary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax)
Description
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Time Frame
0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
Title
Time to reach maximum concentration (tmax)
Description
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Time Frame
0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
Title
Area under the concentration-time curve (AUC)
Description
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Time Frame
0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
Title
Half life (t1/2)
Description
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Time Frame
0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
Title
Incidence of adverse events
Description
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Time Frame
Day 1 and Day 7 on each treatment
Title
Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
Description
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Time Frame
Day 1 and Day 8 on each treatment
Title
Changes in vital signs and physical examination findings
Description
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Time Frame
Day 1 and Day 8 on each treatment
Title
Incidence of adverse events
Description
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Time Frame
Day 42 of the study as follow up
Title
Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
Description
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Time Frame
Day 42 of the study as follow up
Title
Changes in vital signs and physical examination findings
Description
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Time Frame
Day 42 of the study as follow up
Other Pre-specified Outcome Measures:
Title
Change in Urinary pH
Description
To evaluate the relationship between the doses of uralyt and urinary pH under the administration of RDEA3170.
Time Frame
baseline and day 7 on each treatment
Title
Deoxyribonucleic acid polymorphism
Description
To collect and store deoxyribonucleic acid (DNA) for future exploratory research.
Time Frame
Day 1 of the study as randomization
Title
Change in Serum uric acid level
Description
% change per treatment will be compared.
Time Frame
Baseline and day 7 on each treatment for cohort 6
Title
Change in Urinary excretion of uric acid
Description
Timed urinary uric acid excretion per treatment will be compared.
Time Frame
Baseline and day 7 on each treatment for cohort 6
Title
Renal clearance of uric acid
Description
Renal clearance of uric acid will be calculated.
Time Frame
Baseline and day 7 on each treatment for cohort 6
Title
Fractional excretion of uric acid
Description
Fractional excretion and renal clearance of uric acid will be calculated.
Time Frame
Baseline and day 7 on each treatment for cohort 6

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Research Site
City
Fukuoka-shi
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
32951150
Citation
Rekic D, Johansson S, Leander J. Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight. Clin Pharmacokinet. 2021 Mar;60(3):319-328. doi: 10.1007/s40262-020-00943-6. Epub 2020 Sep 19.
Results Reference
derived
PubMed Identifier
29868853
Citation
Shiramoto M, Liu S, Shen Z, Yan X, Yamamoto A, Gillen M, Ito Y, Hall J. Verinurad combined with febuxostat in Japanese adults with gout or asymptomatic hyperuricaemia: a phase 2a, open-label study. Rheumatology (Oxford). 2018 Sep 1;57(9):1602-1610. doi: 10.1093/rheumatology/key100.
Results Reference
derived

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

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