Phase 2a RDEA3170 and Allopurinol Combination Study in Gout Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Drug: RDEA3170 2.5 mg; Drug: allopurinol 300 mg

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
  • Florida
    • DeLand, Florida, United States, 32720
    • South Miami, Florida, United States, 33143
  • Texas
    • Dallas, Texas, United States, 75231

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RDEA3170 2.5 mg, 7.5 mg and 15 mg; RDEA3170 2.5 mg, 7.5 mg and 15 mg once daily (qd) in combination with allopurinol 300 mg (qd and twice daily (bid))	Drug: RDEA3170 2.5 mg; Cohort 1: RDEA3170 2.5 mg, 7.5 mg (2.5 mg × 3 tablets), and 15 mg (2.5 mg × 6 tablets). Cohort 2: RDEA3170 5 mg (2.5 mg × 2 tablets), 10 mg (2.5 mg × 4 tablets), and 20 mg (2.5 mg × 8 tablets).; Drug: allopurinol 300 mg; allopurinol 300 mg, allopurinol 600 mg (300 mg x 2 tablets)
Experimental: RDEA3170 5 mg, 10 mg and 20 mg; RDEA3170 5 mg, 10 mg 20 mg qd in combination with allopurinol 300 mg (qd and bid)	Drug: RDEA3170 2.5 mg; Cohort 1: RDEA3170 2.5 mg, 7.5 mg (2.5 mg × 3 tablets), and 15 mg (2.5 mg × 6 tablets). Cohort 2: RDEA3170 5 mg (2.5 mg × 2 tablets), 10 mg (2.5 mg × 4 tablets), and 20 mg (2.5 mg × 8 tablets).; Drug: allopurinol 300 mg; allopurinol 300 mg, allopurinol 600 mg (300 mg x 2 tablets)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%))	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1)	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
Cohort 1 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol.	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1)	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
Cohort 1 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%))	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1)	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
Cohort 1 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%))	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1)	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
Cohort 2 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%))	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2)	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
Cohort 2 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol.	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2)	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
Cohort 2 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%))	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2)	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)
Cohort 2 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%))	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2)	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax)	Cmax of Allopurinol alone or in combination with RDEA3170	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
Time of Occurrence of Maximum Observed Concentration (Tmax)	Tmax of Allopurinol alone or in combination with RDEA3170	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)	AUC 0-24 of Allopurinol alone or in combination with RDEA3170	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)	AUC last of Allopurinol alone or in combination with RDEA3170	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
Apparent Terminal Half-life (t1/2)	t1/2 of Allopurinol alone or in combination with RDEA3170	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)
Number of Participants With Treatment-Emergent Adverse Events		11 weeks

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.
• Investigators: Study Director: Jesse Hall, MD, Ardea Biosciences, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2015
• Primary Completion (Actual): November 19, 2015
• Study Completion (Actual): June 2, 2016

Study Registration Dates

• First Submitted: July 13, 2015
• First Submitted That Met QC Criteria: July 13, 2015
• First Posted (Estimate): July 15, 2015

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: December 20, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Allopurinol; Verinurad
• Other Study ID Numbers: RDEA3170-206