Phase 2a RDEA3170 and Allopurinol Combination Study in Gout Subjects

NCT02498652 | Completed Phase 2 Results DMC

• 1 other identifier: RDEA3170-206
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 4

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.

Conditions

Gout

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (6)

• Maximum Observed Concentration (Cmax)

  Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)

• Time of Occurrence of Maximum Observed Concentration (Tmax)

  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)

  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)

  Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)

• Apparent Terminal Half-life (t1/2)

  Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)

Study Arms (2)

RDEA3170 2.5 mg, 7.5 mg and 15 mg

EXPERIMENTAL

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; Drug: allopurinol 300 mg

RDEA3170 5 mg, 10 mg and 20 mg

EXPERIMENTAL

RDEA3170 5 mg, 10 mg 20 mg qd in combination with allopurinol 300 mg (qd and bid)

Drug: RDEA3170 2.5 mg; Drug: allopurinol 300 mg

Interventions

RDEA3170 2.5 mg DRUG

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).

RDEA3170 2.5 mg, 7.5 mg and 15 mg; RDEA3170 5 mg, 10 mg and 20 mg

allopurinol 300 mg DRUG

allopurinol 300 mg, allopurinol 600 mg (300 mg x 2 tablets)

RDEA3170 2.5 mg, 7.5 mg and 15 mg; RDEA3170 5 mg, 10 mg and 20 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:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ardea Biosciences, Inc.: lead

Study Sites (4)

Unknown Facility

Anaheim, California, 92801, United States

Location

Unknown Facility

DeLand, Florida, 32720, United States

Location

Unknown Facility

South Miami, Florida, 33143, United States

Location

Unknown Facility

Dallas, Texas, 75231, United States

Location

Related Publications (1)

• 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.

  PMID: 29531784 DERIVED

MeSH Terms

Conditions

Gout

Interventions

verinurad; Allopurinol

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)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Reliable urine uric acid values were not obtained due to sample processing errors, and this has resulted in the inability to assess the PD effects of RDEA3170 and/or allopurinol in urine.

Results Point of Contact

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

information.center@astrazeneca.com

(877) 240-9479

Study Officials

• Jesse Hall, MD

  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: July 13, 2015
• First Posted: July 15, 2015
• Study Start: July 28, 2015
• Primary Completion: November 19, 2015
• Study Completion: June 2, 2016
• Last Updated: January 23, 2018
• Results First Posted: January 23, 2018

Record last verified: 2017-12

Locations

US (4)