Pharmacokinetics of Verinurad and Allopurinol in Combination With Cyclosporine and Rifampicin in Healthy Volunteers

Inclusion Criteria

• Provision of signed and dated, written informed consent form prior to any study specific procedures.
• Healthy male or female subjects aged 18 - 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
• Females must be either (1) Of non-childbearing potential, confirmed at Screening by fulfilling one of the following criteria (i) Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and Follicle-stimulating hormone (FSH) levels in the post-menopausal range (FSH >40 IU/mL).

(ii) Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

• Male subjects must adhere to the contraception methods.
• Have a body mass index between 18 and 30 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive).
• Must be able to swallow multiple capsules/tablets.

Exclusion Criteria

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
• Subject has a positive test result for severe acute respiratory syndrome coronavirus 2 before dosing in Treatment Period 1.
• Has clinical signs and symptoms consistent with coronavirus disease 2019 (COVID-19) infection, eg fever, dry cough, dyspnea, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
• History of severe COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated).
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks prior to the first administration of verinurad.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at Screening (Visit 1) and on first admission (Day -1 in Treatment Period 1) as judged by the Investigator, including:

Alanine aminotransferase >1.5 × Upper limit of normal (ULN) Aspartate aminotransferase >1.5 × ULN Bilirubin (total) >1.5 × ULN Gamma glutamyl transpeptidase >1.5 × ULN If any of these tests are out of range, the test can be repeated once at the Screening Visit at the discretion of the Investigator.

• Any clinically significant abnormal findings in vital signs at Screening Visit and/or on admission (Day -1 in Treatment Period 1) to the Clinical Unit, including, but not limited to, any of the following:
• Systolic blood pressure 140 mmHg and/or diastolic blood pressure 90 mmHg sustained for more than 10 minutes while resting in a supine position
• Heart rate (resting, supine) 90 bpm
• Any clinically significant abnormalities on 12-lead electrocardiogram at Screening Visit, as judged by the Investigator, including, but not limited to any of the following:
• QTcF > 450 ms or 240 ms); intermittent second or third degree atrioventricular (AV) block, or AV dissociation,
• Complete bundle branch block and/or QRS duration > 120 ms.
• Any positive result at Screening Visit for serum hepatitis B surface antigen or anti-hepatitis B core antibody, hepatitis C antibody, and human immunodeficiency virus antibody.
• Suspicion or known Gilbert's and/or Lesch-Nyhan syndrome
• History of hypersensitivity to drugs with a similar chemical structure or class to verinurad, allopurinol, cyclosporine or rifampicin or excipients.
• Subjects who wear soft contact lenses (due to possible staining from rifampicin), unless the subject is prepared to refrain from wearing soft lenses throughout Treatment Period 3 until after the last PK sample collection.
• Women of childbearing potential.
• Carrier of the Huma