RDEA3170 and Febuxostat Combination Study in Gout Subjects

NCT02246673 | Completed Phase 2 Results

• 1 other identifier: RDEA3170-204
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Gout

Outcome Measures

Primary Outcomes (4)

• Serum Urate Maximum Percentage (%) Change (Emax, CB)

  Maximum observed percentage (%) change from baseline in serum urate concentrations.

  28 days

• Urine Uric Acid % Change (0-24h) (Aeur, CB)

  Percentage (%) change from baseline in the amount of uric acid recovered in urine.

  28 days

• Renal Clearance of Uric Acid % Change (0-24h) (CLur, CB)

  Percentage (%) change from baseline in renal clearance of uric acid.

  28 days

• Fract. Excretion of Uric Acid % Change (0-24h) (FEUA, CB)

  Percentage (%) change from baseline in fractional excretion of uric acid.

  28 days

Secondary Outcomes (6)

• Maximum Observed Plasma Concentration (Cmax)

  Days 7 to 28

• Time of Occurrence of Maximum Observed Concentration (Tmax)

  Days 7 to 28

• Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)

  Days 7 to 28

• Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)

  Days 7 to 28

• Apparent Terminal Half-life (t1/2)

  Days 7 to 28

Study Arms (4)

RDEA3170 10 mg

EXPERIMENTAL

Once daily (qd) with febuxostat 40mg (qd) for 7 days, and with febuxostat 80 mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.

Drug: RDEA3170 10 mg; Drug: Febuxostat 40 mg; Drug: Febuxostat 80 mg

RDEA3170 15 mg

EXPERIMENTAL

Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.

Drug: RDEA3170 15 mg; Drug: RDEA3170 5 mg; Drug: Febuxostat 40 mg; Drug: Febuxostat 80 mg

RDEA3170 5 mg

EXPERIMENTAL

Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.

Drug: Febuxostat 40 mg; Drug: Febuxostat 80 mg

RDEA3170 2.5 mg

EXPERIMENTAL

Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days.

Drug: RDEA3170 2.5; Drug: Febuxostat 40 mg; Drug: Febuxostat 80 mg

Interventions

RDEA3170 15 mg DRUG

RDEA3170 15 mg

RDEA3170 10 mg DRUG

RDEA3170 10 mg

RDEA3170 2.5 DRUG

RDEA3170 2.5 mg

RDEA3170 5 mg DRUG

RDEA3170 15 mg

Febuxostat 40 mg DRUG

RDEA3170 10 mg; RDEA3170 15 mg; RDEA3170 2.5 mg; RDEA3170 5 mg

Febuxostat 80 mg DRUG

RDEA3170 10 mg; RDEA3170 15 mg; RDEA3170 2.5 mg; RDEA3170 5 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand the study procedures and the risks involved and is willing to provide written informed consent before the first study-related activity.
• 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.
• Body weight ≥ 50 kg (110 lbs) and a body mass index ≥ 18 and ≤ 45 kg/m2.
• Screening serum urate level ≥ 8 mg/dL.
• Free of any clinically significant disease or medical condition, per the Investigator's judgment.

You may not qualify if:

• Unable to take colchicine for gout flare prophylaxis.
• History or suspicion of kidney stones.
• Any gastrointestinal disorder that affects motility and/or absorption.
• 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.
• Screening laboratory parameters that are outside the normal limits and are considered clinically significant by the Investigator.
• Estimated creatinine clearance \< 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight during the Screening period.
• 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.
• 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.

Sponsors & Collaborators

• Ardea Biosciences, Inc.: lead

Study Sites (6)

Unknown Facility

Anaheim, California, 92801, United States

Location

Unknown Facility

Glendale, California, 91206, United States

Location

Unknown Facility

South Miami, Florida, 33143, United States

Location

Unknown Facility

Overland Park, Kansas, 66211, United States

Location

Unknown Facility

Overland Park, Kansas, 66212, United States

Location

Unknown Facility

Dallas, Texas, 75231, United States

Location

Related Publications (2)

• 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.

  PMID: 32951150 DERIVED

• Fleischmann R, Winkle P, Hall J, Valdez S, Liu S, Yan X, Hicks L, Lee C, Miner JN, Gillen M, Hernandez-Illas M. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with febuxostat in adults with gout: a phase IIa, open-label study. RMD Open. 2018 Apr 9;4(1):e000647. doi: 10.1136/rmdopen-2018-000647. eCollection 2018.

  PMID: 29657831 DERIVED

MeSH Terms

Conditions

Gout

Interventions

verinurad; Febuxostat

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jesse Hall, MD
• Organization: Study Information Center AstraZeneca

information.center@astrazeneca.com

+1 877-240-9479

Study Officials

• J. Hall

  Ardea Biosciences, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2014
• First Posted: September 23, 2014
• Study Start: October 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: February 1, 2016
• Last Updated: July 27, 2017
• Results First Posted: July 27, 2017

Record last verified: 2017-06

Locations

US (6)