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

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

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.

Study Overview

• Status: Completed
• Conditions: Gout and Asymptomatic Hyperuricemia
• Intervention / Treatment: Drug: RDEA3170; Drug: Febuxostat; Drug: Benzbromarone

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-shi, Japan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: RDEA3170; Oral Treatment; Drug: Febuxostat; Oral Treatment
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.	Drug: RDEA3170; Oral Treatment; Drug: Febuxostat; Oral Treatment
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.	Drug: RDEA3170; Oral Treatment; Drug: Febuxostat; Oral Treatment
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.	Drug: RDEA3170; Oral Treatment; Drug: Febuxostat; Oral Treatment
Experimental: Cohort 5; RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg	Drug: RDEA3170; Oral Treatment
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.	Drug: RDEA3170; Oral Treatment; Drug: Febuxostat; Oral Treatment; Drug: Benzbromarone; Oral Treatment

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax)	To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.	0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
Time to reach maximum concentration (tmax)	To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.	0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
Area under the concentration-time curve (AUC)	To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.	0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
Half life (t1/2)	To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.	0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each 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	Day 1 and Day 7 on each treatment
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	Day 1 and Day 8 on each treatment
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	Day 1 and Day 8 on each 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	Day 42 of the study as follow up
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	Day 42 of the study as follow up
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	Day 42 of the study as follow up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Urinary pH	To evaluate the relationship between the doses of uralyt and urinary pH under the administration of RDEA3170.	baseline and day 7 on each treatment
Deoxyribonucleic acid polymorphism	To collect and store deoxyribonucleic acid (DNA) for future exploratory research.	Day 1 of the study as randomization
Change in Serum uric acid level	% change per treatment will be compared.	Baseline and day 7 on each treatment for cohort 6
Change in Urinary excretion of uric acid	Timed urinary uric acid excretion per treatment will be compared.	Baseline and day 7 on each treatment for cohort 6
Renal clearance of uric acid	Renal clearance of uric acid will be calculated.	Baseline and day 7 on each treatment for cohort 6
Fractional excretion of uric acid	Fractional excretion and renal clearance of uric acid will be calculated.	Baseline and day 7 on each treatment for cohort 6

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Ardea Biosciences, Inc.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: December 9, 2014
• First Submitted That Met QC Criteria: December 16, 2014
• First Posted (Estimate): December 17, 2014

Study Record Updates

• Last Update Posted (Estimate): June 12, 2015
• Last Update Submitted That Met QC Criteria: June 11, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Hyperuricemia; Gout; Antirheumatic Agents; Gout Suppressants; Renal Agents; Uricosuric Agents; Febuxostat; Verinurad; Benzbromarone
• Other Study ID Numbers: D5491L00001; RDEA3170-205 (Other Identifier: Ardea Biosciences, Inc.)