A Study to Assess the Safety and Pharmacokinetics of Verinurad and Allopurinol in Asian and Chinese Subjects
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a randomized, placebo controlled, double-blind study with two separate cohorts to
      assess safety, tolerability and pharmacokinetics of verinurad and allopurinol in healthy
      subjects.

      In cohort 1, twelve Asian subjects will be treated with allopurinol 300mg for 7 days followed
      by either allopurinol 300mg and verinurad 24mg or matching placebo for 7 days.

      In Cohort 2, nine Chinese subjects will be treated with allopurinol 300mg for 7 days followed
      by allopurinol 300mg and verinurad 12mg administered on 7 out of 8 days.
    

Detailed description: 
      This is a Phase I study with 2 parallel cohorts which will be performed at a single study
      center.

      Cohort-1 will comprise of 12 healthy Asian participants, and will follow a randomized,
      double-blind, placebo-controlled design. The number of Chinese participants included in
      Cohort 1 must be less than 50% of the total number of participants enrolled into the cohort.
      Nine participants will be randomized to receive 24 mg verinurad and 300 mg allopurinol once
      daily for 7 days and 3 participants will be randomized to receive matching placebos once
      daily for 7 days. Cohort 1 participants will undergo a Screening Period of a maximum of 28
      days followed by a 7-day Run-in Period during which participants will receive 300 mg
      allopurinol or matching placebo once daily. Participants will then be randomized before the
      start of the Run-in Period. The Run-in Period is intended to decrease the risk of skin
      toxicity of allopurinol. Participants will be admitted to the clinical unit 2-days before the
      treatment period, during which they will receive once daily doses of 24 mg verinurad and 300
      mg allopurinol or matching placebos. Participants will be discharged from the clinical unit
      on Day 8, but will return for a Follow-up Visit within 7 to 14 days.

      Cohort-2 will comprise of 9 healthy Chinese participants and will follow an open-label
      design. All 9 Chinese participants will receive 12 mg verinurad and 300 mg allopurinol on Day
      1 and Day 3 to Day 9. For Cohort-2, participants will undergo a Screening Period of a maximum
      of 28 days followed by a 7-day Run-in Period during which participants will receive 300 mg
      allopurinol once daily. Participants will be admitted to the Clinical Unit on Day -2, and
      will receive a single dose of 12 mg verinurad and 300 mg allopurinol on Day 1. No dosing will
      be done on Day 2. Participants will continue dosing on Day 3 and will be dosed once daily
      until Day 9. Participants will be discharged from the Clinical Unit on Day 10, but will
      return for a Follow-up Visit within 7 to 14 days.
    

Intervention name(s): Verinurad; Allopurinol; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Participants will receive verinurad 24 mg in cohort 1 and 12 mg in cohort 2 once daily.; Participants will receive allopurinol 300 mg once daily.; During Run-in Period, participants in cohort 1 will receive placebo matching allopurinol capsule once daily from Day -7 to Day -1. During treatment period, participants in cohort 1 will receive placebo matching allopurinol capsule and placebo matching verinurad capsule once daily from Day 1 to Day 7.
Intervention MeSH terms: Allopurinol; Verinurad
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Uric acid transporter 1 (URAT1) Inhibitor; Xantine oxidoreductase inhibitor; Pharmacokinetics; Verinurad; Allopurinol