Drug-drug Interaction Study With Metformin and Imatinib

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01404715
Recruitment Status : Completed
First Posted : July 28, 2011
Last Update Posted : April 10, 2014
National Institutes of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
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 or disease Intervention/treatment Phase
Healthy Drug: Metformin Drug: Imatinib Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pharmacokinetic Interaction Between Metformin and Imatinib in Healthy Volunteers.
Study Start Date : October 2011
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Investigate the effect of the co-administration of imatinib on the pharmacokinetics of metformin in healthy volunteers. [ Time Frame: 24 hours ]
    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)

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01404715

United States, California
Ucsf Ctsi Crc
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
National Institutes of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Principal Investigator: Kathleen Giacomini, Ph.D University of California, San Francisco

Responsible Party: University of California, San Francisco Identifier: NCT01404715     History of Changes
Other Study ID Numbers: 6367
R01GM036780 ( U.S. NIH Grant/Contract )
First Posted: July 28, 2011    Key Record Dates
Last Update Posted: April 10, 2014
Last Verified: April 2014

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

Additional relevant MeSH terms:
Imatinib Mesylate
Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action