Clinical trial NCT02317861: A PD/Safety Study of RDEA3170 in Combination With Febuxostat for Treating Gout or Asymptomatic Hyperuricemia Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Gout and Asymptomatic Hyperuricemia
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Ardea Biosciences, Inc.
First posted: 2014-12-17
Enrollment: 110
Sex: MALE
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Serum uric acid level
timeFrame: baseline and day 7 on each treatment
measure: Change in Urinary excretion of uric acid
timeFrame: baseline and day 7 on each treatment
measure: Renal clearance of uric acid
timeFrame: baseline and day 7 on each treatment
measure: Fractional excretion of uric acid
timeFrame: baseline and day 7 on each treatment
Secondary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
measure: Time to reach maximum concentration (tmax)
timeFrame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
measure: Area under the concentration-time curve (AUC)
timeFrame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
measure: Half life (t1/2)
timeFrame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
measure: Incidence of adverse events
timeFrame: Day 1 and Day 7 on each treatment
measure: Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
timeFrame: Day 1 and Day 8 on each treatment
measure: Changes in vital signs and physical examination findings
timeFrame: Day 1 and Day 8 on each treatment
measure: Incidence of adverse events
timeFrame: Day 42 of the study as follow up
measure: Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
timeFrame: Day 42 of the study as follow up
measure: Changes in vital signs and physical examination findings
timeFrame: Day 42 of the study as follow up
Other outcomes:
measure: Change in Urinary pH
timeFrame: baseline and day 7 on each treatment
measure: Deoxyribonucleic acid polymorphism
timeFrame: Day 1 of the study as randomization
measure: Change in Serum uric acid level
timeFrame: Baseline and day 7 on each treatment for cohort 6
measure: Change in Urinary excretion of uric acid
timeFrame: Baseline and day 7 on each treatment for cohort 6
measure: Renal clearance of uric acid
timeFrame: Baseline and day 7 on each treatment for cohort 6
measure: Fractional excretion of uric acid
timeFrame: Baseline and day 7 on each treatment for cohort 6
Locations:
city: Fukuoka-shi
country: Japan
facility: Research Site
Study officials:
References:
citation: 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.
citation: 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.