A Study to Assess the Effect of Intensive Uric Acid (UA) Lowering Therapy With RDEA3170, Febuxostat, Dapagliflozin on Urinary Excretion of UA
Condition: Asymptomatic Hyperuricemia
MeSH terms: Hyperuricemia
Intervention: Verinurad; Febuxostat; Dapagliflozin; Dapagliflozin matched placebo
Intervention description: Randomized patients will receive orally once daily fixed dose of verinurad in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo; Randomized patients will receive orally once daily fixed dose of febuxostat in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo; Randomized patients will receive orally once daily fixed dose of dapagliflozin in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo; Randomized patients will receive orally once daily fixed dose of dapagliflozin matched placebo in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo
Intervention MeSH terms: Dapagliflozin; Febuxostat; Verinurad
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Masking description: The pharmacokineticist will remain blinded during the study conduct, unless otherwise required based on study findings. The pharmacokineticist will be unblinded to perform the final PK analyses after all patients have completed the study, final bioanalytical results are available and all required study data are considered clean. This may occur before database lock.
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Gout; Uric acid; Hyperuricemia; Asymptomatic gout; Febuxostat; Dapagliflozin; Uric acid transporter 1 (URAT1) Inhibitor; Xanthine Oxidase Inhibitor; Sodium-glucose cotransporter 2 (SGLT2) Inhibitor

Summary:

      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
    

Eligibility criteria:

        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.