Gout and Asymptomatic Hyperuricemia
Conditions
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.
Interventions
Sponsors
Ardea Biosciences, Inc.
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum uric acid level | baseline and day 7 on each treatment | % change per treatment will be compared. |
| Fractional excretion of uric acid | baseline and day 7 on each treatment | Fractional excretion and renal clearance of uric acid will be calculated. |
| Renal clearance of uric acid | baseline and day 7 on each treatment | Renal clearance of uric acid will be calculated. |
| Change in Urinary excretion of uric acid | baseline and day 7 on each treatment | Timed urinary uric acid excretion per treatment will be compared |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve (AUC) | 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. |
| Maximum plasma concentration (Cmax) | 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) | 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) | 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 | 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 | 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 | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Fractional excretion of uric acid | Baseline and day 7 on each treatment for cohort 6 | Fractional excretion and renal clearance of uric acid will be calculated. |
| Change in Serum uric acid level | Baseline and day 7 on each treatment for cohort 6 | % change per treatment will be compared. |
| Deoxyribonucleic acid polymorphism | Day 1 of the study as randomization | To collect and store deoxyribonucleic acid (DNA) for future exploratory research. |
| Change in Urinary pH | baseline and day 7 on each treatment | To evaluate the relationship between the doses of uralyt and urinary pH under the administration of RDEA3170. |
| Renal clearance of uric acid | Baseline and day 7 on each treatment for cohort 6 | Renal clearance of uric acid will be calculated. |
| Change in Urinary excretion of uric acid | Baseline and day 7 on each treatment for cohort 6 | Timed urinary uric acid excretion per treatment will be compared. |
Countries
Japan
Outcome results
None listed