A PD/Safety Study of RDEA3170 in Combination With Febuxostat for Treating Gout or Asymptomatic Hyperuricemia Patients
- Conditions
- Gout and Asymptomatic Hyperuricemia
- Interventions
- Registration Number
- NCT02317861
- Lead Sponsor
- AstraZeneca
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 110
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 RDEA3170 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. Cohort 2 Febuxostat 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. Cohort 2 RDEA3170 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. Cohort 5 RDEA3170 RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg Cohort 3 RDEA3170 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. Cohort 1 Febuxostat 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. Cohort 4 RDEA3170 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. Cohort 6 RDEA3170 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. Cohort 3 Febuxostat 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. Cohort 4 Febuxostat 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. Cohort 6 Febuxostat 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. Cohort 6 Benzbromarone 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.
- Primary Outcome Measures
Name Time Method Change in Serum uric acid level baseline and day 7 on each treatment % change per treatment will be compared.
Change in Urinary excretion of uric acid baseline and day 7 on each treatment Timed urinary uric acid excretion per treatment will be compared
Renal clearance of uric acid baseline and day 7 on each treatment Renal clearance of uric acid will be calculated.
Fractional excretion of uric acid baseline and day 7 on each treatment Fractional excretion and renal clearance of uric acid will be calculated.
- Secondary Outcome Measures
Name Time Method 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.
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.
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 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 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 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
Trial Locations
- Locations (1)
Research Site
🇯🇵Fukuoka-shi, Japan