Phase 2a RDEA3170 and Allopurinol Combination Study in Gout Subjects

Phase 2

Completed

• Conditions: Gout
• Interventions: Drug: RDEA3170 2.5 mg; Drug: allopurinol 300 mg

• Registration Number: NCT02498652
• Lead Sponsor: Ardea Biosciences, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-07-13
• Study First Submitted QC: 2015-07-13
• Study First Posted: 2015-07-15
• Study Start: 2015-07-28
• Primary Completion: 2015-11-19
• Study Completion: 2016-06-02
• Results First Submitted: 2017-07-17
• Status Verified: 2017-12
• Results First Submitted QC: 2017-12-20
• Last Update Submitted: 2017-12-20
• Results First Posted: 2018-01-23
• Last Update Posted: 2018-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RDEA3170 5 mg, 10 mg and 20 mg	RDEA3170 2.5 mg	RDEA3170 5 mg, 10 mg 20 mg qd in combination with allopurinol 300 mg (qd and bid)
RDEA3170 5 mg, 10 mg and 20 mg	allopurinol 300 mg	RDEA3170 5 mg, 10 mg 20 mg qd in combination with allopurinol 300 mg (qd and bid)
RDEA3170 2.5 mg, 7.5 mg and 15 mg	RDEA3170 2.5 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))
RDEA3170 2.5 mg, 7.5 mg and 15 mg	allopurinol 300 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))

Primary Outcome Measures

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

Secondary Outcome Measures

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