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The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics

The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02956278
Enrollment
27
Registered
2016-11-07
Start date
2016-11-30
Completion date
2018-03-31
Last updated
2020-06-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Gout, Hyperuricemia

Keywords

allopurinol

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.

Interventions

DRUGAllopurinol
OTHERPlacebo

lactose placebo pill

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
CollaboratorNIH
Open Medicine Institute
CollaboratorUNKNOWN
University of California, San Francisco
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Oxypurinol Renal Clearance24 hours (Urine collected 0-4 hrs,4-8 hrs,8-10 hrs,10-24 hrs post-dose)Renal clearance as defined by amount excreted in 24 hours/AUC from 0-24 hours
Percent Change Uric Acid24 hoursMaximum percent change in uric acid after a single dose of allopurinol

Secondary

MeasureTime frameDescription
Oxypurinol AUC24 hours (Collections at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 24 hours post-dose)Area under the concentration time curve from 0-24 hours following a single dose of allopurinol (i.e. Day 1 of both protocols)

Countries

United States

Participant flow

Pre-assignment details

As the intent of the protocol was to characterize the effect of the genetic variant, data were collected and analyzed per genotype variant regardless of number of doses received.

Participants by arm

ArmCount
BCRP Q141K CC Genotype
All subjects that completed the protocol with the reference BCRP Q141K genotype (CC alleles)
9
BCRP Q141K CA Genotype
All subjects that completed the protocol with the heterozygous BCRP Q141K genotype (CA alleles)
7
BCRP Q141K AA Genotype
All subjects that completed the protocol with the homozygous BCRP Q141K genotype (AA alleles)
3
Total19

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyWithdrawal by Subject620

Baseline characteristics

CharacteristicTotalBCRP Q141K CC GenotypeBCRP Q141K CA GenotypeBCRP Q141K AA Genotype
Age, Continuous27.7 years
STANDARD_DEVIATION 6.1
26.9 years
STANDARD_DEVIATION 5.7
29.0 years
STANDARD_DEVIATION 7.2
27.3 years
STANDARD_DEVIATION 6.5
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
15 Participants6 Participants7 Participants2 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
3 Participants2 Participants0 Participants1 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
1 Participants1 Participants0 Participants0 Participants
Sex: Female, Male
Female
7 Participants5 Participants1 Participants1 Participants
Sex: Female, Male
Male
12 Participants4 Participants6 Participants2 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 150 / 90 / 3
other
Total, other adverse events
0 / 150 / 90 / 3
serious
Total, serious adverse events
0 / 150 / 90 / 3

Outcome results

Primary

Oxypurinol Renal Clearance

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)

ArmMeasureValue (MEAN)Dispersion
BCRP Q141K CC GenotypeOxypurinol Renal Clearance1.9 L/hrStandard Deviation 1.2
BCRP Q141K CA GenotypeOxypurinol Renal Clearance1.4 L/hrStandard Deviation 0.5
BCRP Q141K AA GenotypeOxypurinol Renal Clearance1.6 L/hrStandard Deviation 0.9
Primary

Percent Change Uric Acid

Maximum percent change in uric acid after a single dose of allopurinol

Time frame: 24 hours

Population: Baseline and minimum SUA level after a single dose of allopurinol (i.e. Day 1) were used for the calculation (baseline-minimum)/baseline)

ArmMeasureValue (MEAN)Dispersion
BCRP Q141K CC GenotypePercent Change Uric Acid26.8 Percent Change from BaselineStandard Deviation 5.9
BCRP Q141K CA GenotypePercent Change Uric Acid23.8 Percent Change from BaselineStandard Deviation 7
BCRP Q141K AA GenotypePercent Change Uric Acid21.4 Percent Change from BaselineStandard Deviation 2.5
Secondary

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)

Time frame: 24 hours (Collections at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 24 hours post-dose)

ArmMeasureValue (MEAN)Dispersion
BCRP Q141K CC GenotypeOxypurinol AUC95.9 mcg*hr/mLStandard Deviation 25.1
BCRP Q141K CA GenotypeOxypurinol AUC99.1 mcg*hr/mLStandard Deviation 30.1
BCRP Q141K AA GenotypeOxypurinol AUC108.5 mcg*hr/mLStandard Deviation 36.1

Source: ClinicalTrials.gov · Data processed: Feb 15, 2026