RDEA3170 and Allopurinol Combination Study in Gout Subjects

A Phase 1b, Randomized, Open-label Study to Evaluate the Potential Pharmacokinetic and Pharmacodynamic Interactions Between RDEA3170 and Allopurinol in Adult Male Subjects With Gout

This is a Phase 1b, randomized, open-label, drug-drug interaction study in adult male subjects with gout. It is designed to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of RDEA3170 or allopurinol alone and in combination in the fed state.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Drug: RDEA3170 10 mg; Drug: allopurinol 300 mg

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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 and ≤ 10 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 an estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight at Screening prior to Day -2.
• Subject is on unstable doses of chronic medications. Subjects taking medications for chronic medical conditions must be on stable doses during the course of the study, including the Screening period. Dose adjustments are allowed if deemed medically necessary by the investigator and following discussion with the medical monitor
• Chronic and stable doses of losartan, fenofibrate, guaifenesin, and sodium-glucose linked transporter-2 inhibitors are permitted if the dose is 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: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A; RDEA3170 qd (once daily), RDEA3170 + allopurinol qd, allopurinol qd	Drug: RDEA3170 10 mg; Drug: allopurinol 300 mg
Experimental: Sequence B; allopurinol qd, RDEA3170 + allopurinol qd, RDEA3170 qd	Drug: RDEA3170 10 mg; Drug: allopurinol 300 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)	Cmax of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170	22 days
Time of Occurrence of Maximum Observed Concentration (Tmax)	Tmax of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination	22 days
Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)	AUC 0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170	22 days
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)	AUC last of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170	22 days
Apparent Terminal Half-life (t1/2)	t1/2 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination	22 days
Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24)	Ae0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170	22 days
Renal Clearance of the Drug From Time Zero up to 24 Hours Postdose (CRL0-24)	CLR0-24 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination	22 days
Pharmacodynamics (PD) Profile of Uric Acid From Serum and Urine		22 days
Maximum Observed Plasma Concentration (Cmax)	Cmax of RDEA3170 Alone and In Combination with Allopurinol	22 days
Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)	AUC 0-24 of RDEA3170 Alone and In Combination with Allopurinol	22 days
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)	AUC last of RDEA3170 Alone and In Combination with Allopurinol	22 days
Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24)	Ae0-24 of RDEA3170 Alone and In Combination with Allopurinol	22 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-Emergent Adverse Events	22 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): April 6, 2015
• Study Completion (Actual): September 11, 2015

Study Registration Dates

• First Submitted: October 28, 2014
• First Submitted That Met QC Criteria: October 30, 2014
• First Posted (Estimate): October 31, 2014

Study Record Updates

• Last Update Posted (Actual): December 20, 2017
• Last Update Submitted That Met QC Criteria: December 19, 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: RDEA3170-107