Effect of a Proton Pump Inhibitor on Gleevec® in Healthy Volunteers

NCT ID: NCT00446004

Last Updated: 2016-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2009-08-31

Brief Summary

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.

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: OTHER

Imatinib Mesylate

Intervention Type: DRUG

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)

Omeprazole

Intervention Type: DRUG

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).

Group Type: OTHER

Imatinib Mesylate

Intervention Type: DRUG

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)

Omeprazole

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Gleevec®; Prilosec®; Proton Pump Inhibitor

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Jan Beumer

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jan H. Beumer, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh Cancer Institute / Clinical and Translational Research Center (Hillman Cancer Center and Montefiore University Hospital locations)

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

CSTI571BUS258

Identifier Type: OTHER

Identifier Source: secondary_id

06-074

Identifier Type: -

Identifier Source: org_study_id