A Study to Assess the Safety and Pharmacokinetics of Verinurad and Allopurinol in Asian and Chinese Subjects
Status: | Recruiting |
---|---|
Conditions: | Renal Impairment / Chronic Kidney Disease |
Therapuetic Areas: | Nephrology / Urology |
Healthy: | No |
Age Range: | 18 - 50 |
Updated: | 4/4/2019 |
Start Date: | January 16, 2019 |
End Date: | May 6, 2019 |
Contact: | AstraZeneca Clinical Study Information Center |
Email: | information.center@astrazeneca.com |
Phone: | 1-877-240-9479 |
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
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.
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.
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.
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.
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.
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