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
Study type: Interventional
Phase: Phase 2

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
    

Detailed 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.
    

Intervention name(s): Verinurad; Febuxostat; Dapagliflozin; Dapagliflozin matched placebo
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): 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
Other intervention name(s): RDEA3170; ULORIC; FARXIGA
Intervention MeSH terms: Dapagliflozin; Febuxostat; Verinurad
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Gout; Uric acid; Hyperuricemia; Asymptomatic gout; Febuxostat; Dapagliflozin; Uric acid transporter 1 (URAT1) Inhibitor; Xanthine Oxidase Inhibitor; Sodium-glucose cotransporter 2 (SGLT2) Inhibitor