Drug-drug Interaction Study With Metformin and Imatinib

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01404715
First received: July 13, 2011
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

This study will address the following question: Does imatinib influence the pharmacokinetics of metformin in healthy volunteers? Recent studies in the Giacomini laboratory have indicated that imatinib may block metformin elimination from the kidney by inhibiting organic cation transporter efflux of metformin. 1. The investigators hypothesize that the addition of imatinib to metformin therapy will reduce the renal clearance (CLR) of metformin leading to increased plasma concentrations and risk for toxicities 2. Knowledge of the pharmacokinetic interaction profile of metformin with organic cation transporter inhibitors, such as imatinib, is important to help develop safer more effective drug therapy with reduced side effects.


Condition Intervention Phase
Healthy
Drug: Metformin
Drug: Imatinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Pharmacokinetic Interaction Between Metformin and Imatinib in Healthy Volunteers.

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Investigate the effect of the co-administration of imatinib on the pharmacokinetics of metformin in healthy volunteers. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Cmax and Tmax will be determined from AUC-time curve Glomerular filtration rate (GFR) will be approximated by measured creatinine clearance using the following equation:GFR calculation: GFR = CLcreatinine = (Urinary creatinine * V) / (Plasma creatinine)


Enrollment: 11
Study Start Date: October 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin and Imatinib Co-Adminisdered
Subjects will be dosed with Metformin (1850 mg) in conjunction with imatinib (600mg).
Drug: Imatinib
A single oral dose of 600 mg of imatinib
Other Name: GLEEVEC
Experimental: Metformin Alone
Subjects will be dosed with Metformin alone (1850mg)
Drug: Metformin
Subjects will be given an oral dose of 1000 mg of metformin followed by an oral dose of 850 mg for a grand total of 1850 mg in both study Arm 1 and study Arm 2.
Other Name: GLUCOPHAGE

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18-45 years
  • Male or female
  • If female, using appropriate contraception
  • Healthy as judged by medical examination, medical history and normal biochemical and hematological measures
  • Normal urinalysis and renal function
  • Understand the nature and purpose of the study and provide informed consent

Exclusion Criteria:

  • Pregnant or lactating woman (female subjects will have a urine pregnancy test at the screening visit)
  • Abnormal bone marrow function (leukocyte, neutrophil, or platelet counts outside the normal range)
  • History of hypersensitivity or allergic reaction to metformin or imatinib
  • Risk of congestive heart failure requiring pharmacologic treatment (medical history)
  • History of renal or hepatic dysfunction (e.g., CLcr <60mL/min, ALT >80U/L, AST>60 U/L) Anemic (hemoglobin <12 g/dL)
  • Use of any medications (including over the counter products, herbal products, or mineral supplements) with the exception of a daily vitamin or oral contraceptives. In particular use of medications that are known to interfere with the pharmacokinetics of metformin and imatinib such as cimetidine, cetirizine, ketoconazole, procainamide, St. John's Wort, and testosterone are prohibited.
  • 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
  • Laboratory parameters that are more than 2 standard deviations from the laboratory mean
  • Subject carries a MATE1 gene variant that is predicted to effect MATE1 protein expression
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01404715

Locations
United States, California
Ucsf Ctsi Crc
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Kathleen Giacomini, Ph.D University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01404715     History of Changes
Other Study ID Numbers: 6367, R01GM036780
Study First Received: July 13, 2011
Last Updated: April 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Drug drug interaction

Additional relevant MeSH terms:
Imatinib
Metformin
Antineoplastic Agents
Enzyme Inhibitors
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014