Trial Outcomes & Findings for Organic Cation Transporter 1 (OCT1), on Response to Metformin in Healthy Subjects (NCT NCT00187681)

Results Overview

To test whether individuals with genetic variants of human organic cation transporter, OCT1, exhibit altered pharmacokinetics of metformin, the difference in AUC of blood concentration-time of metformin between reference and variant groups will be measured.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

20 participants

Primary outcome timeframe

0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours

Results posted on

2013-01-08

Participant Flow

Participant milestones

Participant milestones
Measure	Organic Cation Transporter 1 (OCT1)-Variant Group Subjects with OCT1-variant alleles to be dosed with 2 doses of Metformin (total 1850 mg).	Organic Cation Transporter 1 (OCT1)-Reference Group Subjects with OCT1-reference alleles to be dosed with 2 doses of Metformin (total 1850 mg).
Overall Study STARTED	12	8
Overall Study COMPLETED	12	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Organic Cation Transporter 1 (OCT1), on Response to Metformin in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OCT1-variant Group n=12 Participants Subjects with OCT1-reference alleles to be doses with 2 doses of Metformin (total 1850 mg).	OCT1-reference Group n=8 Participants Subjects with OCT1-reference alleles to be doses with 2 doses of Metformin (total 1850 mg).	Total n=20 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	30.0 years STANDARD_DEVIATION 5.9 • n=5 Participants	31.3 years STANDARD_DEVIATION 5.4 • n=7 Participants	30.5 years STANDARD_DEVIATION 5.6 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	8 participants n=7 Participants	20 participants n=5 Participants

PRIMARY outcome

Timeframe: 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours

Population: 20 participants were analyzed as per protocol. The sample size of 20 subjects enabled us to detect a significant difference (at the p \< 0.05 level; α = 0.05, β = 0.80) in the pharmacokinetics of metformin between individuals who are homozygous for the reference OCT1 and those who carry an OCT1-R61C, OCT1-G401S or OCT1-G465R allele.

To test whether individuals with genetic variants of human organic cation transporter, OCT1, exhibit altered pharmacokinetics of metformin, the difference in AUC of blood concentration-time of metformin between reference and variant groups will be measured.

Outcome measures

Outcome measures
Measure	OCT1-variant Group n=12 Participants Metformin blood concentration-time profiles in subjects carrying the variant OCT1 genotypes (ie. carries at least one of the four variant alleles OCT1-R61C, G401S, 420del, and/or OCT1-G465R).	OCT1-reference Group n=8 Participants Metformin blood concentration-time profiles in subjects carrying the reference OCT1 allele at all the four positions in the OCT1 gene.
Area Under the Curve (AUC) of Blood Concentration-time of Metformin	9,200 hour * µg/L Standard Deviation 1,200	7,700 hour * µg/L Standard Deviation 970

PRIMARY outcome

Timeframe: 0 to 180 minutes

Population: 20 participants were analyzed as per protocol. The sample size of 20 subjects enabled us to detect a significant difference (at the p \< 0.05 level; α = 0.05, β = 0.80) in the pharmacodynamics of metformin between individuals who are homozygous for the reference OCT1 and those who carry an OCT1-R61C, OCT1-G401S or OCT1-G465R allele.

To test whether individuals with genetic variants of human organic cation transporter, OCT1, exhibit altered glucose lowering response to metformin we will measure the difference in area under the glucose concentrations-time curve (Glucose AUC) following oral glucose tolerance test.

Outcome measures

Outcome measures
Measure	OCT1-variant Group n=12 Participants Metformin blood concentration-time profiles in subjects carrying the variant OCT1 genotypes (ie. carries at least one of the four variant alleles OCT1-R61C, G401S, 420del, and/or OCT1-G465R).	OCT1-reference Group n=8 Participants Metformin blood concentration-time profiles in subjects carrying the reference OCT1 allele at all the four positions in the OCT1 gene.
Glucose Lowering Response to Metformin	18,200 min * mg/dL Standard Deviation 1,600	21,300 min * mg/dL Standard Deviation 2,290

Adverse Events

OCT1-variant Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

OCT1-reference Group

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, Ph.D

UCSF

Phone: 4154761936

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place