RDEA3170 and Allopurinol Combination Study in Gout Subjects

• RDEA3170 10 mg (Drug)
• allopurinol 300 mg (Drug)

Primary outcomes

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

Secondary outcomes

• Incidence of Treatment-Emergent Adverse Events [22 days]

Sex: Male, ages: 18 Years to 75 Years

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.

Participant flow

Outcome results

• Maximum Observed Plasma Concentration (Cmax) (Primary), Geometric mean, μg/mL: Allopurinol: Allopurinol Alone 1.13 (0.894 to 1.43); Allopurinol: RDEA3170 + Allopurinol 1.51 (1.24 to 1.82); Oxypurinol: Allopurinol Alone 12.8 (11.7 to 14.0); Oxypurinol: RDEA3170 + Allopurinol 8.68 (7.99 to 9.43)
• Time of Occurrence of Maximum Observed Concentration (Tmax) (Primary), Median, hr: Allopurinol: Allopurinol Alone 1.50 (1.00 to 4.00); Allopurinol: RDEA3170 + Allopurinol 1.25 (0.500 to 4.00); Oxypurinol: Allopurinol Alone 4.00 (1.50 to 6.00); Oxypurinol: RDEA3170 + Allopurinol 3.50 (1.50 to 8.00); RDEA3170: RDEA3170 Alone 3.00 (1.50 to 4.00); RDEA3170: RDEA3170 + Allopurinol 3.00 (2.00 to 10.0)
• Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) (Primary), Geometric mean, μg·hr/mL: Allopurinol: Allopurinol Alone 3.69 (3.24 to 4.21); Allopurinol: RDEA3170 + Allopurinol 3.68 (3.28 to 4.13); Oxypurinol: Allopurinol Alone 255 (229 to 284); Oxypurinol: RDEA3170 + Allopurinol 157 (140 to 177); RDEA3170: RDEA3170 + Allopurinol 115 (96.5 to 137)
• Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) (Primary), Geometric mean, μg·hr/mL: Allopurinol: Allopurinol Alone 3.50 (3.04 to 4.04); Allopurinol: RDEA3170 + Allopurinol 3.61 (3.22 to 4.05); Oxypurinol: Allopurinol Alone 255 (229 to 284); Oxypurinol: RDEA3170 + Allopurinol 157 (140 to 177)
• Apparent Terminal Half-life (t1/2) (Primary), Geometric mean, hr: Allopurinol: Allopurinol Alone 1.06 (0.969 to 1.15); Allopurinol: RDEA3170 + Allopurinol 0.992 (0.890 to 1.10); Oxypurinol: Allopurinol Alone 43.2 (36.1 to 51.7); Oxypurinol: RDEA3170 + Allopurinol 29.1 (23.9 to 35.4); RDEA3170: RDEA3170 Alone 11.5 (8.43 to 15.6); RDEA3170: RDEA3170 + Allopurinol 12.5 (8.99 to 17.4)
• Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) (Primary), Geometric mean, mg: Allopurinol: Allopurinol Alone 25.4 (22.1 to 29.2); Allopurinol: RDEA3170 + Allopurinol 22.7 (19.2 to 26.9); Oxypurinol: Allopurinol Alone 231 (216 to 248); Oxypurinol: RDEA3170 + Allopurinol 275 (262 to 290)
• Renal Clearance of the Drug From Time Zero up to 24 Hours Postdose (CRL0-24) (Primary), Geometric mean, mL/min: Allopurinol: Allopurinol Alone 120 (106 to 135); Allopurinol: RDEA3170 + Allopurinol 103 (87.1 to 122); Oxypurinol: Allopurinol Alone 15.1 (13.0 to 17.6); Oxypurinol: RDEA3170 + Allopurinol 29.2 (25.1 to 33.9); RDEA3170: RDEA3170 Alone 9.28 (7.43 to 11.6); RDEA3170: RDEA3170 + Allopurinol 9.75 (7.73 to 12.3)
• Pharmacodynamics (PD) Profile of Uric Acid From Serum and Urine (Primary), Mean, Percentage (%): RDEA3170: RDEA3170 Alone -50.5 (13.0 to 17.6); Oxypurinol: RDEA3170 + Allopurinol -65.2 (25.1 to 33.9); Allopurinol: Allopurinol Alone -43.0 (7.43 to 11.6)
• Incidence of Treatment-Emergent Adverse Events (Secondary), Number, Number of participants: RDEA3170: RDEA3170 Alone 2 (13.0 to 17.6); Oxypurinol: RDEA3170 + Allopurinol 1 (25.1 to 33.9); Allopurinol: Allopurinol Alone 3 (7.43 to 11.6)
• Maximum Observed Plasma Concentration (Cmax) (Primary), Geometric mean, ng/mL: RDEA3170: RDEA3170 Alone 14.6 (12.2 to 17.5); RDEA3170: RDEA3170 + Allopurinol 14.5 (11.7 to 17.9)
• Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) (Primary), Geometric mean, μg*hr/mL: RDEA3170: RDEA3170 Alone 120 (98.1 to 147); RDEA3170: RDEA3170 + Allopurinol 115 (96.5 to 137)
• Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) (Primary), Geometric mean, ng·hr/mL: RDEA3170: RDEA3170 Alone 120 (98.1 to 147); RDEA3170: RDEA3170 + Allopurinol 115 (96.5 to 137)
• Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) (Primary), Geometric mean, ug: RDEA3170: RDEA3170 Alone 66.8 (51.8 to 86.1); RDEA3170: RDEA3170 + Allopurinol 67.2 (51.7 to 87.4)

Adverse events

Time frame: 22 days

Other adverse events by term

• J. Hall, MD, Study director, Ardea Biosciences, Inc.