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

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.

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.