A PD/Safety Study of RDEA3170 in Combination With Febuxostat for Treating Gout or Asymptomatic Hyperuricemia Patients

AstraZeneca

Status and phase: Completed; Phase 2; Phase 1

Conditions: Gout and Asymptomatic Hyperuricemia

Treatments: Drug: Benzbromarone; Drug: Febuxostat; Drug: RDEA3170

Study type: Interventional

Funder types: Industry

Identifiers

NCT02317861

D5491L00001

RDEA3170-205 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to explore the pharmacodynamics (PD), pharmacokinetics (PK), safety, and tolerability of multiple doses of RDEA3170 administered in combination with febuxostat compared to RDEA3170 administered alone and febuxostat administered alone in Japanese adult male subjects with gout or asymptomatic hyperuricemia.

Enrollment: 110 patients

Sex: Male

Ages: 20 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Screening serum uric acid level ≥ 8 mg/dL;
• Body weight ≥ 50 kg and a body mass index (BMI) ≥ 18 and ≤ 40 kg/m2;
• Free of any clinically significant disease or medical condition, per the Investigator's judgment.

Exclusion criteria

• History or suspicion of kidney stones;
• Diagnosis of benign prostatic hypertrophy (BPH) or neurogenic bladder or evidence of BPH/neurogenic bladder such as thin urinary stream or difficulty in urination;
• An estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula;
• QTcF interval (QT interval corrected for heart rate using Fridericia's formula) > 450 msec at Screening;
• Receiving strong or moderate Cytochrome P450 (CYP) 3A inhibitors or p-glycoprotein inhibitors, or digoxin

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 6 patient groups

Cohort 1

Experimental group

Description:

The half of patients randomized to this cohort will be dosed in the order of Febuxostat 10mg, RDEA3170 2.5 mg + Febuxostat 10mg, RDEA3170 2.5 mg + Febuxostat 20mg, and Febuxostat 20mg. The other half will be dosed in the reverse order.

Treatment:

Drug: Febuxostat

Drug: RDEA3170

Cohort 2

Experimental group

Description:

The half of patients randomized to this cohort will be dosed in the order of Febuxostat 10mg, RDEA3170 5 mg + Febuxostat 10mg, RDEA3170 5 mg + Febuxostat 20mg, and Febuxostat 20mg. The other half will be dosed in the reverse order.

Treatment:

Drug: Febuxostat

Drug: RDEA3170

Cohort 3

Experimental group

Description:

The half of patients randomized to this cohort will be dosed in the order of Febuxostat 20mg, RDEA3170 5 mg + Febuxostat 20mg, RDEA3170 5 mg + Febuxostat 40mg, and Febuxostat 40mg. The other half will be dosed in the reverse order.

Treatment:

Drug: Febuxostat

Drug: RDEA3170

Cohort 4

Experimental group

Description:

The half of patients randomized to this cohort will be dosed in the order of Febuxostat 20mg, RDEA3170 10 mg + Febuxostat 20mg, RDEA3170 10 mg + Febuxostat 40mg, and Febuxostat 40mg. The other half will be dosed in the reverse order.

Treatment:

Drug: Febuxostat

Drug: RDEA3170

Cohort 5

Experimental group

Description:

RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg

Treatment:

Drug: RDEA3170

Cohort 6

Experimental group

Description:

The half of patients randomized to this cohort will be dosed in the order of Benzbromarone 50 mg, Febuxostat 10mg+RDEA3170 2.5 mg, then Febuxostat 20mg+RDEA3170 5 mg. The other half will be dosed in the order of Febuxostat 10mg+RDEA3170 2.5 mg, Febuxostat 20mg+RDEA3170 5 mg, then Benzbromarone 50mg.

Treatment:

Drug: Benzbromarone

Drug: Febuxostat

Drug: RDEA3170