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

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00446004
First received: March 8, 2007
Last updated: January 9, 2014
Last verified: January 2014

March 8, 2007
January 9, 2014
April 2007
August 2009   (final data collection date for primary outcome measure)
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 ]
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.
Complete list of historical versions of study NCT00446004 on ClinicalTrials.gov Archive Site
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Effect of a Proton Pump Inhibitor on Gleevec® in Healthy Volunteers
Effect of a Proton Pump Inhibitor (Omeprazole, Prilosec®) on Imatinib Mesylate (Gleevec®) Pharmacokinetics in Healthy Volunteers (CSTI571BUS258)

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Healthy
  • 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)
    Other Name: Gleevec®
  • 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)
    Other Names:
    • Prilosec®
    • Proton Pump Inhibitor
  • 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).
    Interventions:
    • Drug: Imatinib Mesylate
    • Drug: Omeprazole
  • 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).
    Interventions:
    • Drug: Imatinib Mesylate
    • Drug: Omeprazole
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
August 2009
August 2009   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00446004
06-074, CSTI571BUS258
Not Provided
University of Pittsburgh
University of Pittsburgh
Novartis
Principal Investigator: Jan H. Beumer, PharmD, PhD University of Pittsburgh
University of Pittsburgh
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP