Effect of a Proton Pump Inhibitor on Gleevec® in Healthy Volunteers - Full Text View

Sponsors and Collaborators:	University of Pittsburgh Novartis
Information provided by:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00446004

Purpose

This is a research study that will investigate the effects of proton pump inhibitors (often used to treat stomach upset) on Gleevec® (a drug that is FDA-approved to treat some types of cancer) in healthy volunteers. Twelve healthy volunteers (six men and six women) will be recruited to complete the study. This research study will compare Gleevec® in the body when taken with and without proton pump inhibitors (PPI). Each volunteer will receive a 400 mg pill of Gleevec® on two occasions. On one occasion they will take the dose of Gleevec® alone (without PPI). On another occasion, they will take the Gleevec® after taking 40 mg of PPI daily by mouth for six days. Several blood samples will be drawn to measure the concentrations of Gleevec® and its breakdown products in the blood, with and without the influence of PPI.

Condition	Intervention
Healthy	Drug: Imatinib Mesylate Drug: Omeprazole

Drug Information available for: Imatinib Imatinib mesylate Esomeprazole magnesium Esomeprazole Sodium Omeprazole Omeprazole magnesium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Pharmacokinetics Study
Official Title:	Effect of a Proton Pump Inhibitor (Omeprazole, Prilosec®) on Imatinib Mesylate (Gleevec®) Pharmacokinetics in Healthy Volunteers (CSTI571BUS258)

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

To define the effect of omeprazole administration on the pharmacokinetics (in particular the area under the Gleevec® plasma concentration versus time curve) of Gleevec® in healthy volunteers. [ Time Frame: PK blood samples are drawn from each subject at time 0 (before each dose of Gleevec®), and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hrs after adminstration of Gleevec®. ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	April 2007
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A On an 18-day schedule, Omeprazole (PPI) once daily on days 10 through 16; and Gleevec® once daily on days 1 and 15 (i.e., Gleevec® alone on day 1, and combination of Gleevec® and PPI on day 15).	Drug: Imatinib Mesylate Dosage form: tablets Dosage: 400 mg Frequency & duration: On an 18-day schedule, one dose administered once on day 1 and once on day 15 (2 doses total) Drug: Omeprazole Dosage form: capsules Dosage: 40 mg Frequency: On an 18-day schedule, once daily day 10 through day 16 (for Arm A); or once daily day -4 through day 1 (for Arm B)
B On an 18-day schedule, Omeprazole (PPI) once daily on days -4 through 1; and Gleevec® once daily on days 1 and 15 (i.e., combination of Gleevec® and PPI on day 1, Gleevec® alone on day 15).	Drug: Imatinib Mesylate Dosage form: tablets Dosage: 400 mg Frequency & duration: On an 18-day schedule, one dose administered once on day 1 and once on day 15 (2 doses total) Drug: Omeprazole Dosage form: capsules Dosage: 40 mg Frequency: On an 18-day schedule, once daily day 10 through day 16 (for Arm A); or once daily day -4 through day 1 (for Arm B)

Detailed Description:

This is an open-label, single-institution, randomized cross-over, fixed schedule study of the effects of proton pump inhibitors (PPI) on Imatinib Mesylate (Gleevec®) pharmacokinetics. Healthy volunteers will be recruited to participate in this study such that twelve subjects (6 men / 6 women) will complete the study. Gleevec® pharmacokinetics will be assessed after oral administration of Gleevec® and after oral administration of Gleevec® with concomitant administration of PPI (Prilosec® Delayed-Release Capsules). Gleevec® will be administered at a dose of 400 mg, and the PPI (Prilosec®) at a dose level of 40 mg daily for 6 consecutive days. Half of the subjects will receive Prilosec® starting 5 days before Day 1 through Day 1 along with Gleevec® on Day 1, and Gleevec® alone on Day 15. The other half will receive Prilosec® on Days 10-15, along with Gleevec® on Day 15, and Gleevec® alone on Day 1. On days that both drugs are administered, the Prilosec® will be administered 15 minutes before the Gleevec® dose.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy men or women 18 years of age or older. Healthy subjects are defined as individuals who are free from clinically significant illness or disease (such as coronary arterial disease, chronic heart failure, bleeding disorder, hypertension, chronic renal failure etc.) as determined by their medical history, physical examination, and laboratory studies.
Body Mass Index (BMI) < 31 kg/m^2 (weight/height^2).
Female subjects of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female subjects of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 7 days following discontinuation of study drug.
Written, voluntary informed consent.
Subjects participating in the protocol entitled "IRB: 0701014: Effect of Antacids (Mg-Al-based) on Imatinib Mesylate (Gleevec®) Pharmacokinetics in Healthy Volunteers (CSTI571BUS257) (UPCI #06-088)" will be eligible for participation in this study provided they meet all other eligibility criteria for this study.

Exclusion Criteria:

Abnormal marrow function as defined by leucocyte, neutrophil, or platelet counts outside of normal limits.
Any evidence of renal dysfunction (proteinuria; serum creatinine > upper limit of normal; or if serum creatinine > upper limit of normal, a calculated creatinine clearance < 60 mL/min/1.73 m2).
Impaired hepatic function (liver enzymes greater than the upper limit of normal or bilirubin outside the normal range).
Taking any medications (including over the counter products), herbal products, mineral supplements or vitamins (other than a daily multivitamin preparation), other than contraceptives (for women), within 2 weeks of start of the study. All forms of contraceptive medication are permissible for this study and would not result in a female's exclusion from participation. Patients who take medications on a chronic basis, such as antihypertensive medications or thyroid replacement therapy, etc. are not eligible for the study.
Subjects that have received any other investigational agents within 28 days of first day of study drug dosing.
Female subjects who are pregnant or breast-feeding.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00446004

Contacts

Contact: Jan H. Beumer, PharmD, PhD

412-623-3216

beumerjh@upmc.edu

Locations

United States, Pennsylvania
University of Pittsburgh Cancer Institute / Clinical and Translational Research Center (Hillman Cancer Center and Montefiore University Hospital locations)	Recruiting
Pittsburgh, Pennsylvania, United States, 15232 / 15213
Principal Investigator: Jan H. Beumer, PharmD, PhD
Sub-Investigator: Merrill J. Egorin, M.D.
Sub-Investigator: Robert L. Redner, M.D.
Sub-Investigator: Ronald G. Stoller, M.D.
Sub-Investigator: Leonard J. Appleman, M.D., Ph.D.

Sponsors and Collaborators

University of Pittsburgh

Novartis

Investigators

Principal Investigator:

Jan H. Beumer, PharmD, PhD

University of Pittsburgh

More Information

Responsible Party:	University of Pittsburgh ( Jan Beumer, PharmD, PhD )
Study ID Numbers:	06-074, CSTI571BUS258
Study First Received:	March 8, 2007
Last Updated:	August 7, 2008
ClinicalTrials.gov Identifier:	NCT00446004
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Pittsburgh:

Pharmacokinetics
Healthy volunteers
No condition
Pharmacokinetics study

Study placed in the following topic categories:

Imatinib
Omeprazole
Healthy

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Anti-Ulcer Agents

Gastrointestinal Agents
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009