The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics
Primary Purpose
Chronic Gout, Hyperuricemia
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Allopurinol
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Chronic Gout focused on measuring allopurinol
Eligibility Criteria
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
Sites / Locations
- Open Medicine Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
BCRP Q141K CC
BCRP Q141K CA
BCRP Q141K AA
Arm 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.
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.
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.
Outcomes
Primary Outcome Measures
Oxypurinol Renal Clearance
Renal clearance as defined by amount excreted in 24 hours/AUC from 0-24 hours
Percent Change Uric Acid
Maximum percent change in uric acid after a single dose of allopurinol
Secondary Outcome Measures
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)
Full Information
NCT ID
NCT02956278
First Posted
November 2, 2016
Last Updated
June 9, 2020
Sponsor
University of California, San Francisco
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Open Medicine Institute
1. Study Identification
Unique Protocol Identification Number
NCT02956278
Brief Title
The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics
Official Title
The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
November 2016 (Actual)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
March 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Open Medicine Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Gout, Hyperuricemia
Keywords
allopurinol
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BCRP Q141K CC
Arm Type
Placebo Comparator
Arm 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.
Arm Title
BCRP Q141K CA
Arm Type
Experimental
Arm 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.
Arm Title
BCRP Q141K AA
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Other Intervention Name(s)
Zyloprim, Aloprim
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
lactose placebo pill
Primary Outcome Measure Information:
Title
Oxypurinol Renal Clearance
Description
Renal clearance as defined by amount excreted in 24 hours/AUC from 0-24 hours
Time Frame
24 hours (Urine collected 0-4 hrs,4-8 hrs,8-10 hrs,10-24 hrs post-dose)
Title
Percent Change Uric Acid
Description
Maximum percent change in uric acid after a single dose of allopurinol
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Oxypurinol AUC
Description
Area under the concentration time curve from 0-24 hours following a single dose of allopurinol (i.e. Day 1 of both protocols)
Time Frame
24 hours (Collections at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 24 hours post-dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathleen Giacomini, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Open Medicine Institute
City
Mountain View
State/Province
California
ZIP/Postal Code
94040
Country
United States
12. IPD Sharing Statement
Learn more about this trial
The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics
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