A Study to Assess the Effect of Intensive Uric Acid (UA) Lowering Therapy With RDEA3170, Febuxostat, Dapagliflozin on Urinary Excretion of UA

AstraZeneca

Status and phase: Completed; Phase 2

Conditions: Asymptomatic Hyperuricemia

Treatments: Other: Dapagliflozin matched placebo; Drug: Dapagliflozin; Drug: Verinurad; Drug: Febuxostat

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT03316131

D5495C00001

Details and patient eligibility

About

This is a randomized, placebo controlled, double-blind, 2-way crossover study conducted on asymptomatic hyperuricemic patients. The core study consists of screening period, 2 treatment periods (verinurad + febuxostat + dapagliflozin/placebo) and follow-up visit

Full description

This is a randomized, placebo controlled, double-blind, 2-way crossover study to assess the effect of intensive UA lowering therapy with verinurad (RDEA3170), febuxostat, and dapagliflozin on urinary excretion of UA, in asymptomatic hyperuricemic patients. Thirty-six asymptomatic hyperuricemic patients aged 18 to 65 years (inclusive) will be enrolled into this study at 2 study centers. Twenty-four patients have been enrolled and completed the study to date. Due to inadequate urine sampling, 12 additional patients were included to ensure an adequate sample size (at least 20 evaluable patients) to evaluate the effects of intensive UA lowering with verinurad, febuxostat and dapagliflozin on urinary excretion of UA. With 24 completers available during the interim analysis, this will provide for a total sample size of 36 evaluable patients.

Before any study specific assessments are performed, potential patients must provide informed consent. Each patient will undergo the below mentioned visits:

• A Screening period of maximum 28 days;
• Two treatment periods during which patients will be resident in the Clinical Unit from Day -2 to Day 1 and from Day 6 to Day 8; and
• A Follow-up Visit within 14 to 28 days after the first administration of Investigational Medicinal Product (IMP) in Treatment Period 2.

On Day -2 of Treatment period 1, patient will be randomized (1:1) to 1 of 2 treatment sequences (AB or BA). Each randomized patient will receive orally once daily fixed dose of the below mentioned 2 treatments for 7 consecutive days (1 treatment per treatment period).

• Treatment A: Verinurad + febuxostat + dapagliflozin
• Treatment B: Verinurad + febuxostat + placebo For each treatment period, baseline measurements will be performed. On Day 1, after all dosing and all assessments have been performed, patients will receive instruction to administer the IMP at home once daily in the morning from Day 2 to Day 6 and the IMP will be dispensed for home dosing. Patients will return to the Clinical Unit on Day 6 and will be residential in the Clinical Unit from Day 6 to Day 8.

Treatment Period 1 and Treatment Period 2 will be separated by a washout period of 7 to 21 days.

Patients will return to the Clinical Unit for a Follow-up Visit, 14 to 28 days after Day 1 of Treatment Period 2.

Enrollment: 36 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 18 to 65 years old
2. Asymptomatic hyperuricemia (sUA > 6.0 mg/dL)
3. Body mass index between 18 and 35 kg/m2 inclusive and weight at least 50 kg and no more than 150 kg
4. Females must be non-pregnant, as well as post-menopausal or willing to use an acceptable method of contraception during the study.

Exclusion criteria

1. History of any clinically significant disease or disorder putting the patient at risk during the study, or influencing study results or ability to participate in the study
2. eGFR* < 45 mL/minute/1.73 m2 at Screening.
3. Type 2 diabetes mellitus with HbA1c >8%.
4. History of diabetic ketoacidosis, hyperosmolar non-ketotic coma, gout, or alcohol or drug abuse.
5. Ongoing treatment with an SGLT2-inhibitor, a URAT1-inhibitor, and/or a xanthine oxidase inhibitor.
6. Positive test for hepatitis B, hepatitis C or HIV.
7. Use of any medications in the 2 weeks preceding first administration of study drug.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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36 participants in 2 patient groups

Treatment A

Experimental group

Description:

Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin;

Treatment:

Drug: Febuxostat

Drug: Verinurad

Drug: Dapagliflozin

Treatment B

Experimental group

Description:

Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin matched placebo

Treatment:

Drug: Febuxostat

Other: Dapagliflozin matched placebo

Drug: Verinurad