The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics

University of California San Francisco (UCSF)

Status and phase: Completed; Phase 4

Conditions: Hyperuricemia; Chronic Gout

Treatments: Other: Placebo; Drug: Allopurinol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02956278

R01DK103729 (U.S. NIH Grant/Contract)

14-14550

Details and patient eligibility

About

Subjects will undergo a placebo and allopurinol phase to better understand the effects of the reduced function BCRP Q141K variant on allopurinol pharmacokinetics and pharmacodynamics.

Enrollment: 27 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• self-identified as Asian/European ancestry
• generally healthy with approved lab values for CBC,HFP,RFP, and uric acid
• Subjects with the ABCG2 genotype, homozygous, heterozygous or homozygous for the major allele of rs2231142 will be recruited

Exclusion criteria

• vascular disease
• renal impairment
• medications/supplements that affect uric acid levels
• pregnant or lactating women
• prior history of allergic reaction to allopurinol or testing positive for HLA-B*5801 allele
• risk of urinary or gastric retention or narrow-angle glaucoma
• impaired hepatic function
• evidence of anemia
• evidence or diagnosis of congestive heart failure
• smokers
• subjects with a mutation other than rs2231142 in the ABCG2 genotype
• subjects taking hormonal contraceptives or other hormonal medications
• evidence of recreational drug use as determined by questionnaire

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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27 participants in 3 patient groups, including a placebo group

BCRP Q141K CC

Placebo Comparator group

Description:

Participants that are homozygous reference for BCRP Q141K receive at least one 300 mg dose of allopurinol followed by blood/urine collection for up to 72 hours post-dose.

Treatment:

Other: Placebo

Drug: Allopurinol

BCRP Q141K CA

Experimental group

Description:

Participants that are heterozygous for the BCRP Q141K allele receive at least one 300 mg dose of allopurinol, with blood/urine collections up to 72 hours post-dose.

Treatment:

Other: Placebo

Drug: Allopurinol

BCRP Q141K AA

Experimental group

Description:

Participants homozygous for the BCRP Q141K allele receive at least one 300 mg dose of allopurinol with blood/urine collection for up to 72 hours post-dose.

Treatment:

Other: Placebo

Drug: Allopurinol