A Phase 1 Study to Evaluate the Potential Pharmacokinetic and Pharmacodynamic Interactions Between RDEA3170 and Febuxostat in Healthy Adult Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- RDEA3170 10 mg
- Conditions
- Healthy
- Sponsor
- Ardea Biosciences, Inc.
- Enrollment
- 21
- Primary Endpoint
- PK profile of RDEA3170 from plasma and urine and febuxostat from plasma
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •body weight ≥ 50 kg (110 lbs.) and a body mass index ≥ 18 and ≤ 40 kg/m
- •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
- •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.
Arms & Interventions
Febuxostat
Days 1-7: febuxostat 40 mg qd. Days 8-14: RDEA3170 10 mg or placebo qd in combination with febuxostat 40 mg qd. Days 15-21: RDEA3170 10 mg or placebo qd.
Intervention: RDEA3170 10 mg
Febuxostat
Days 1-7: febuxostat 40 mg qd. Days 8-14: RDEA3170 10 mg or placebo qd in combination with febuxostat 40 mg qd. Days 15-21: RDEA3170 10 mg or placebo qd.
Intervention: Febuxostat 40 mg
Febuxostat
Days 1-7: febuxostat 40 mg qd. Days 8-14: RDEA3170 10 mg or placebo qd in combination with febuxostat 40 mg qd. Days 15-21: RDEA3170 10 mg or placebo qd.
Intervention: placebo
RDEA3170
Days 1-7: RDEA3170 10 mg or placebo qd. Days 8-14: RDEA3170 10 mg or placebo qd in combination with febuxostat 40 mg qd. Days 15-21: febuxostat 40 mg qd.
Intervention: RDEA3170 10 mg
RDEA3170
Days 1-7: RDEA3170 10 mg or placebo qd. Days 8-14: RDEA3170 10 mg or placebo qd in combination with febuxostat 40 mg qd. Days 15-21: febuxostat 40 mg qd.
Intervention: Febuxostat 40 mg
RDEA3170
Days 1-7: RDEA3170 10 mg or placebo qd. Days 8-14: RDEA3170 10 mg or placebo qd in combination with febuxostat 40 mg qd. Days 15-21: febuxostat 40 mg qd.
Intervention: placebo
Outcomes
Primary Outcomes
PK profile of RDEA3170 from plasma and urine and febuxostat from plasma
Time Frame: 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 Outcomes
- Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters(8 weeks)
- PD profile of RDEA3170 and febuxostat alone and in combination(Days -1, 7, 14, 21 and Days 8, 15, 22 (serum only))