Drug-drug Interaction Study With Metformin and Imatinib

NCT01404715 | Completed Phase 1 DMC

• 2 other identifiers: 6367R01GM036780
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Drug drug interaction

Outcome Measures

Primary Outcomes (1)

• Investigate the effect of the co-administration of imatinib on the pharmacokinetics of metformin in healthy volunteers.

  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)

  24 hours

Study Arms (2)

Metformin and Imatinib Co-Adminisdered

EXPERIMENTAL

Subjects will be dosed with Metformin (1850 mg) in conjunction with imatinib (600mg).

Drug: Imatinib

Metformin Alone

EXPERIMENTAL

Subjects will be dosed with Metformin alone (1850mg)

Drug: Metformin

Interventions

Metformin DRUG

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.

Also known as: GLUCOPHAGE

Metformin Alone

Imatinib DRUG

A single oral dose of 600 mg of imatinib

Also known as: GLEEVEC

Metformin and Imatinib Co-Adminisdered

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institutes of Health (NIH): collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Ucsf Ctsi Crc

San Francisco, California, 94143, United States

Location

MeSH Terms

Interventions

Metformin; Imatinib Mesylate

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Kathleen Giacomini, Ph.D

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 13, 2011
• First Posted: July 28, 2011
• Study Start: October 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: April 10, 2014

Record last verified: 2014-04

Locations

US (1)