Healthy
Conditions
Brief summary
This study will evaluate the potential pharmacokinetic (PK) and pharmacodynamic (PD) interaction between the XO inhibitor febuxostat and the investigational URAT1 inhibitor RDEA3170 and provide information for potential future clinical studies using this combination. Combination treatment using 2 drugs with different mechanisms of action may achieve improved response and may allow the use of lower doses, resulting in fewer side effects than the use of either drug alone.
Interventions
DRUGRDEA3170 10 mg
RDEA3170 10 mg once daily (qd)
DRUGFebuxostat 40 mg
Febuxostat 40 mg qd
DRUGplacebo
placebo qd
Sponsors
Ardea Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* body weight ≥ 50 kg (110 lbs.) and a body mass index ≥ 18 and ≤ 40 kg/m2. * no clinically relevant abnormalities in vital signs, ECG, physical examination or safety laboratory values, per the Investigator's judgment. * a screening serum urate level ≥ 4.5 mg/dL.
Exclusion criteria
* history or suspicion of kidney stones. * history of cardiac abnormalities as assessed during screening, including abnormal and clinically relevant electrocardiogram changes and/or family history of sudden death in otherwise healthy individual between the ages of 1 and 30 years. * undergone major surgery within 3 months prior to Day 1. * donated blood or experienced significant blood loss (\> 450 mL) within 12 weeks prior to Day 1 or gave a plasma donation within 4 weeks prior to the Screening Period. * inadequate venous access or unsuitable veins for repeated venipuncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK profile of RDEA3170 from plasma and urine and febuxostat from plasma | Days -1 (urine only), 7, 14, 21 and Days 8, 15, 22 (plasma only) | Profile from plasma and urine in terms of AUC, Tmax, Cmax, t1/2, Ae, and CLr AUC: area under the concentration-time curve; Tmax: time to maximum plasma concentration; Cmax: maximum plasma drug concentration; t1/2: apparent terminal half-life; Ae: amount excreted of unchanged drug into urine; CLr: renal clearance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PD profile of RDEA3170 and febuxostat alone and in combination | Days -1, 7, 14, 21 and Days 8, 15, 22 (serum only) | Profile from serum and urine in terms of sUA concentration, renal clearance of uric acid, urine uric acid excretion amounts, and fractional excretion of uric acid. sUA: serum urate |
| Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters | 8 weeks | — |
Countries
United States
Outcome results
None listed