A Study to Assess the Safety and Pharmacokinetics of Verinurad and Allopurinol in Asian and Chinese Subjects

• Status: Completed
• Trial end date: 2019-04-26
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Parexel
• Treatments: Allopurinol; Verinurad

Criteria

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study specific procedures.

• Applicable only to Cohort 1: Healthy male and female Asian subjects aged 18 to 50 years (inclusive) at the Screening Visit with suitable veins for cannulation or repeated venipuncture. A subject will be considered Asian if the subject and both of the subject's parents are part of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent, including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam).

• Applicable only to Cohort 2: Healthy male and female Chinese subjects aged 18 to 50 years (inclusive) at the Screening Visit with suitable veins for cannulation or repeated venipuncture. A subject will be considered Chinese if:

• Both parents and all grandparents are Chinese, and

• Subject was born in China, and

• Subject has not lived outside China for more than 10 years.

• Subject has a sUA acid level > 4.0 mg/dL at the Screening Visit. The assessment may be repeated once during the Screening Period.

• Females must have a negative pregnancy test at the Screening Visit and Day -7, must not be lactating and must be:

1. Of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria:

• 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 levels > 40 IU/mL).

• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

2. OR if of childbearing potential must be willing to use an acceptable method of contraception to avoid pregnancy for the entire study period.

Exclusion Criteria:

• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at the Screening Visit as judged by the Investigator including:

1. Alanine aminotransferase (ALT) >1.5 x upper limit of normal (ULN);

2. Aspartate aminotransferase (AST) >1.5 x ULN;

3. Bilirubin (total) > 1.5 x ULN; and

4. Gamma glutamyl transpeptidase (GGT) >1.5 x ULN. If any these tests are out-of-range the test can be repeated once at the Screening Visit at the discretion of the Investigator.

• Known carrier of the Human Leukocyte Antigen-B (HLA-B) *58:01 allele.

• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.

• Suspected or known Gilbert's syndrome.

• Current smokers or those who have smoked or used nicotine products (including e-cigarettes within the previous 3 months).

• Positive screen for drugs of abuse, cotinine (nicotine) or alcohol at the Screening Visit or on Day -7.

• Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of investigational product or within 5 half-lives (whichever is longer). The use of hormonal contraception therapy and hormonal replacement therapy for females are permitted.

• Has received another new chemical or biological entity (defined as a compound which has not been approved for marketing in the US) within 30 days or within 5 half-lives (whichever is longer) of the first administration of investigational drug in this study.

• Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.

• Subjects who are vegans or have medical dietary restrictions.