Clinical trial NCT02498652: Phase 2a RDEA3170 and Allopurinol Combination Study in Gout Subjects
Official title: A Phase 2a, Randomized, Open-Label Study to Evaluate the Pharmacodynamic Effects and Safety of RDEA3170 Administered in Combination With Allopurinol Compared With Allopurinol Administered Alone in Adult Subjects With Gout
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gout
Lead sponsor: Ardea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-15
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2a, randomized, open-label, multicenter study to assess the pharmacodynamic (PD) effects of RDEA3170 administered in combination with allopurinol compared with allopurinol administered alone in adult subjects with gout.


Eligibility criteria: Inclusion Criteria:

* Subject is able to understand the study procedures and the risks involved and is willing to provide written informed consent before the first study-related activity.
* Subject meets one or more criteria for the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of Acute Arthritis of Primary Gout.
* Subject has a body weight ≥ 50 kg (110 lbs.) and a body mass index ≥ 18 and ≤ 45 kg/m2.
* Subject has a Screening serum urate level ≥ 8 mg/dL.
* Subject is free of any clinically significant disease or medical condition, per the Investigator's judgment.

Exclusion Criteria:

* Subject is unable to take colchicine for gout flare prophylaxis.
* Subject has a history or suspicion of kidney stones.
* Subject has any gastrointestinal disorder that affects motility and/or absorption.
* Subject had unstable angina, New York Heart Association class III or IV heart failure, ischemic heart disease, stroke, or deep venous thrombosis within 12 months prior to Day 1; or subject is currently receiving anticoagulants.
* Subject has Screening laboratory parameters that are outside the normal limits and are considered clinically significant by the Investigator.
* Subject has an estimated creatinine clearance \< 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight during the Screening period.
* Subject is taking losartan, fenofibrate, guaifenesin, or sodium-glucose linked transporter-2 inhibitors; chronic and stable doses are permitted if doses are stable for at least 14 days prior to study medication dosing.
* Subject is unable or unwilling to comply with the study requirements or has a situation or condition that, in the opinion of the Investigator, may interfere with participation in the study.

Primary outcomes:
measure: Cohort 1 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%))
timeFrame: Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
measure: Cohort 1 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol.
timeFrame: Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
measure: Cohort 1 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%))
timeFrame: Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
measure: Cohort 1 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%))
timeFrame: Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
measure: Cohort 2 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%))
timeFrame: Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
measure: Cohort 2 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol.
timeFrame: Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
measure: Cohort 2 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%))
timeFrame: Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
measure: Cohort 2 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%))
timeFrame: Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax)
timeFrame: Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
measure: Time of Occurrence of Maximum Observed Concentration (Tmax)
timeFrame: Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
measure: Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)
timeFrame: Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
measure: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)
timeFrame: Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
measure: Apparent Terminal Half-life (t1/2)
timeFrame: Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: 11 weeks
Other outcomes:
Locations:
city: Anaheim
country: United States
state: California
city: DeLand
country: United States
state: Florida
city: South Miami
country: United States
state: Florida
city: Dallas
country: United States
state: Texas
Study officials:
affiliation: Ardea Biosciences, Inc.
name: Jesse Hall, MD
role: STUDY_DIRECTOR
References:
citation: Fleischmann R, Winkle P, Miner JN, Yan X, Hicks L, Valdez S, Hall J, Liu S, Shen Z, Gillen M, Hernandez-Illas M. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout: a phase IIa, open-label study. RMD Open. 2018 Feb 8;4(1):e000584. doi: 10.1136/rmdopen-2017-000584. eCollection 2018.