Trial Outcomes & Findings for The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics (NCT NCT02956278)
NCT ID: NCT02956278
Last Updated: 2020-06-23
Results Overview
Renal clearance as defined by amount excreted in 24 hours/AUC from 0-24 hours
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
27 participants
Primary outcome timeframe
24 hours (Urine collected 0-4 hrs,4-8 hrs,8-10 hrs,10-24 hrs post-dose)
Results posted on
2020-06-23
Participant Flow
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.
Participant milestones
| Measure |
BCRP Q141K CC
Participants that are homozygous reference for BCRP Q141K receive one 300 mg dose of allopurinol followed by blood/urine collection for up to 72 hours.
|
BCRP Q141K CA
Participants that are heterozygous for the BCRP Q141K allele receive one 300 mg dose of allopurinol, with blood/urine collections up to 72 hours.
|
BCRP Q141K AA
Participants homozygous for the BCRP Q141K allele receive one 300 mg dose of allopurinol with blood/urine collection for up to 72 hours.
|
|---|---|---|---|
|
Overall Study
STARTED
|
15
|
9
|
3
|
|
Overall Study
COMPLETED
|
9
|
7
|
3
|
|
Overall Study
NOT COMPLETED
|
6
|
2
|
0
|
Reasons for withdrawal
| Measure |
BCRP Q141K CC
Participants that are homozygous reference for BCRP Q141K receive one 300 mg dose of allopurinol followed by blood/urine collection for up to 72 hours.
|
BCRP Q141K CA
Participants that are heterozygous for the BCRP Q141K allele receive one 300 mg dose of allopurinol, with blood/urine collections up to 72 hours.
|
BCRP Q141K AA
Participants homozygous for the BCRP Q141K allele receive one 300 mg dose of allopurinol with blood/urine collection for up to 72 hours.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
6
|
2
|
0
|
Baseline Characteristics
The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics
Baseline characteristics by cohort
| Measure |
BCRP Q141K CC Genotype
n=9 Participants
All subjects that completed the protocol with the reference BCRP Q141K genotype (CC alleles)
|
BCRP Q141K CA Genotype
n=7 Participants
All subjects that completed the protocol with the heterozygous BCRP Q141K genotype (CA alleles)
|
BCRP Q141K AA Genotype
n=3 Participants
All subjects that completed the protocol with the homozygous BCRP Q141K genotype (AA alleles)
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
26.9 years
STANDARD_DEVIATION 5.7 • n=5 Participants
|
29.0 years
STANDARD_DEVIATION 7.2 • n=7 Participants
|
27.3 years
STANDARD_DEVIATION 6.5 • n=5 Participants
|
27.7 years
STANDARD_DEVIATION 6.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 24 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
Outcome measures
| Measure |
BCRP Q141K CC Genotype
n=9 Participants
All subjects that completed the protocol with the reference BCRP Q141K genotype (CC alleles)
|
BCRP Q141K CA Genotype
n=7 Participants
All subjects that completed the protocol with the heterozygous BCRP Q141K genotype (CA alleles)
|
BCRP Q141K AA Genotype
n=3 Participants
All subjects that completed the protocol with the homozygous BCRP Q141K genotype (AA alleles)
|
|---|---|---|---|
|
Oxypurinol Renal Clearance
|
1.9 L/hr
Standard Deviation 1.2
|
1.4 L/hr
Standard Deviation 0.5
|
1.6 L/hr
Standard Deviation 0.9
|
PRIMARY outcome
Timeframe: 24 hoursPopulation: Baseline and minimum SUA level after a single dose of allopurinol (i.e. Day 1) were used for the calculation (baseline-minimum)/baseline)
Maximum percent change in uric acid after a single dose of allopurinol
Outcome measures
| Measure |
BCRP Q141K CC Genotype
n=9 Participants
All subjects that completed the protocol with the reference BCRP Q141K genotype (CC alleles)
|
BCRP Q141K CA Genotype
n=7 Participants
All subjects that completed the protocol with the heterozygous BCRP Q141K genotype (CA alleles)
|
BCRP Q141K AA Genotype
n=3 Participants
All subjects that completed the protocol with the homozygous BCRP Q141K genotype (AA alleles)
|
|---|---|---|---|
|
Percent Change Uric Acid
|
26.8 Percent Change from Baseline
Standard Deviation 5.9
|
23.8 Percent Change from Baseline
Standard Deviation 7.0
|
21.4 Percent Change from Baseline
Standard Deviation 2.5
|
SECONDARY outcome
Timeframe: 24 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)
Outcome measures
| Measure |
BCRP Q141K CC Genotype
n=9 Participants
All subjects that completed the protocol with the reference BCRP Q141K genotype (CC alleles)
|
BCRP Q141K CA Genotype
n=7 Participants
All subjects that completed the protocol with the heterozygous BCRP Q141K genotype (CA alleles)
|
BCRP Q141K AA Genotype
n=3 Participants
All subjects that completed the protocol with the homozygous BCRP Q141K genotype (AA alleles)
|
|---|---|---|---|
|
Oxypurinol AUC
|
95.9 mcg*hr/mL
Standard Deviation 25.1
|
99.1 mcg*hr/mL
Standard Deviation 30.1
|
108.5 mcg*hr/mL
Standard Deviation 36.1
|
Adverse Events
BCRP Q141K CC
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
BCRP Q141K CA
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
BCRP Q141K AA
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Kathy Giacomini, PhD
University of California San Francisco
Phone: 415-514-4363
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place