A study to assess the safety and pharmacokinetics of verinurad and allopurinol in Asian and Chinese subjects

Study identifier:D5495C00006

ClinicalTrials.gov identifier:NCT03836599

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase I Randomized Double-blind Placebo-controlled Study with 2 Separate Cohorts to Assess the Safety, Tolerability and Pharmacokinetics of Verinurad and Allopurinol in Healthy Asian and Chinese Subjects

Medical condition

Chronic Kidney Disease

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Verinurad, Allopurinol, Placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 50 Years

Date

Study Start Date: 16 Jan 2019

Primary Completion Date: 26 Apr 2019

Study Completion Date: 26 Apr 2019

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2020 by AstraZeneca

Collaborators

PAREXEL Early Phase Clinical Unit

Inclusion and exclusion 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.

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.

Location

Research Site

Glendale, CA, United States, 91206

Arms	Assigned Interventions
Experimental: 24 mg Verinurad+300 mg allopurinol During Run-in Period, participants will be dosed with 300 mg of allopurinol from Day -7 to Day -1. During the Treatment Period, participants will be administered 24 mg verinurad with 300 mg allopurinol once daily on Days 1 to 7.	Drug: Verinurad Participants will receive verinurad 24 mg in cohort 1 and 12 mg in cohort 2 once daily. Drug: Allopurinol Participants will receive allopurinol 300 mg once daily.
Experimental: 12 mg Verinurad+300 mg allopurinol During Run-in Period, participants will be dosed with 300 mg of allopurinol once daily from Day -7 to Day -1. During Treatment Period, participants 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.	Drug: Verinurad Participants will receive verinurad 24 mg in cohort 1 and 12 mg in cohort 2 once daily. Drug: Allopurinol Participants will receive allopurinol 300 mg once daily.
Placebo Comparator: Placebo 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.	Drug: Placebo 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.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

David Han

PAREXEL Early Phase Clinical Unit

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Trial Results Summaries