The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics

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.

Study Overview

• Status: Completed
• Conditions: Hyperuricemia; Chronic Gout
• Intervention / Treatment: Drug: Allopurinol; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Mountain View, California, United States, 94040
      • Open Medicine Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: BCRP Q141K CC; 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.	Drug: Allopurinol; Other Names: Zyloprim; Aloprim; Other: Placebo; lactose placebo pill
Experimental: BCRP Q141K CA; 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.	Drug: Allopurinol; Other Names: Zyloprim; Aloprim; Other: Placebo; lactose placebo pill
Experimental: BCRP Q141K AA; 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.	Drug: Allopurinol; Other Names: Zyloprim; Aloprim; Other: Placebo; lactose placebo pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxypurinol Renal Clearance	Renal clearance as defined by amount excreted in 24 hours/AUC from 0-24 hours	24 hours (Urine collected 0-4 hrs,4-8 hrs,8-10 hrs,10-24 hrs post-dose)
Percent Change Uric Acid	Maximum percent change in uric acid after a single dose of allopurinol	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxypurinol AUC	Area under the concentration time curve from 0-24 hours following a single dose of allopurinol (i.e. Day 1 of both protocols)	24 hours (Collections at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 24 hours post-dose)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Open Medicine Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 6, 2016

Study Record Updates

• Last Update Posted (Actual): June 23, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: allopurinol
• Additional Relevant MeSH Terms: Pathologic Processes; Hyperuricemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Allopurinol
• Other Study ID Numbers: 14-14550; R01DK103729 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No