Effect of Genetic Variation in the Transporter OCT2, MATE1 and MATE2-K on the PKPD of Metformin

NCT01681680 | Completed Phase 1 DMC

• 1 other identifier: 6112
• Study Type: interventional
• Target: 41
• Locations: 0 countries
• Sites: N/A

Brief Summary

The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. The investigators will study individuals with particular genotypes of the human organic cation transporter, (hOCT2), and the multidrug and toxin extrusion transporters, MATE1, MATE2-K to test the hypothesis that genetic variation in hOCT2, hMATEE1 and hMATE2-K are associated with variation in the pharmacokinetics and/or pharmacodynamics of the antidiabetic agent, metformin.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Renal clearance of Metformin based on genotypes

  Renal clearance of Metformin of study participants using reference genotype for transporters of OCT2, MATE1, and MATE2-K. In addition, Cmax for plasma glucose will be analyzed for all study participants.

  Study day procedures 48 hours

Study Arms (1)

Metformin

OTHER

Subjects will be given an oral dose of metformin once per day for two days.

Drug: Metformin

Interventions

Metformin DRUG

Subjects will be given an oral dose of metformin once per day for two days.

Also known as: GLUCOPHAGE

Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects self-identify racial background, identify themselves, parents and four grandparents as Caucasian and or Chinese.
• Subject status is healthy volunteer from the SOPHIE cohort
• Subjects over 18 years old
• Subjects who are healthy on the basis of medical history, physical examinations and laboratory tests if healthy volunteer from SOPHIE
• Subjects who agree with the written informed consent to participate in the study.

You may not qualify if:

• Under 18 years old
• Pregnant or lactating woman (female subjects will have a urine pregnancy test at the Day 1 visit)
• They report a prior history of any allergic reaction to metformin
• Has a risk of congestive heart failure requiring pharmacologic treatment (medical history)
• Has a prior history of renal\* or hepatic dysfunction (renal and hepatic function will be evaluated based on screening blood tests conducted prior to study enrollment)
• Anemic (screening lab values, hemoglobin \<10 g)
• Taking a medication that could confound study results (such as known substrates or inhibitors of OCT2, MATE1 and MATE2-K such as cimetidine)
• Subjects are undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function
• They do not consent to participate in the study

Sponsors & Collaborators

• University of California, San Francisco: lead

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Kathleen M Giacomini, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2012
• First Posted: September 10, 2012
• Study Start: October 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: July 2, 2014

Record last verified: 2014-06