Effect of Calcium on Gleevec Pharmacokinetics (PK) in Healthy Volunteers - Full Text View

Sponsors and Collaborators:	University of Pittsburgh Novartis Pharmaceuticals
Information provided by:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00732784

Purpose

This research study is being conducted through the University of Pittsburgh Cancer Institute (UPCI). It will evaluate the concentrations of Gleevec®, an oral drug used to treat some types of cancer, in the blood of healthy volunteers when taken with and without Tums Ultra®, a calcium product often used in the treatment of upset stomach and as a calcium supplement.

Condition	Intervention
Healthy	Drug: Imatinib mesylate Dietary Supplement: calcium carbonate

MedlinePlus related topics: Calcium Cancer Dietary Supplements

Drug Information available for: Imatinib Imatinib mesylate Calcium gluconate Calcium carbonate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Pharmacokinetics Study
Official Title:	Effect of Calcium Supplements on Imatinib Mesylate (Gleevec®) Pharmacokinetics in Healthy Volunteers (CSTI571BUS 280) (UPCI 08-072)

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

To define the effect of administration of a calcium salt (calcium carbonate) on the PK (in particular the area under the imatinib plasma concentration versus time curve) of imatinib (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:	November 2008
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1 On an 18-day schedule, calcium supplement (Tums Ultra 1000®) once daily on day 15; and Gleevec® once daily on days 1 and 15 (i.e., Gleevec® alone on day 1, and combination of Gleevec® and calcium supplement 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) Dietary Supplement: calcium carbonate Dosage form: tablets Dosage: 4000 mg (4 x 1000 mg tablet) Frequency: On an 18-day schedule, once daily day 15 (for Arm 1); or once daily day 1 (for Arm 2)
2 On an 18-day schedule, calcium supplement (Tums Ultra 1000®) once daily on day 1; and Gleevec® once daily on days 1 and 15 (i.e., combination of Gleevec® and calcium supplement 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) Dietary Supplement: calcium carbonate Dosage form: tablets Dosage: 4000 mg (4 x 1000 mg tablet) Frequency: On an 18-day schedule, once daily day 15 (for Arm 1); or once daily day 1 (for Arm 2)

Detailed Description:

This is an open-label, single-institution, randomized cross-over, fixed-schedule investigation of the effects of calcium carbonate on the pharmacokinetics (PK) of Gleevec® in healthy volunteers. Healthy volunteers will be recruited to participate in this study such that twelve subjects (6 men / 6 women) will complete the study at UPCI. Subjects will be compensated for participation.

Half of the subjects will receive Gleevec® alone on Day 1 and Gleevec® and calcium carbonate on Day 15, and the other half will receive Gleevec® and calcium carbonate on Day 1 and Gleevec® alone on Day 15, determined by randomization of subjects receiving either the combination or Gleevec® alone during the first visit. Doses will be 400 mg Gleevec® and 4000 mg calcium carbonate (4 x Tums Ultra 1000® chewable tablets, equivalent to 4000 mg calcium carbonate or 1600 mg calcium.

Multiple PK blood samples will be taken from Days 1-4 and Days 15-18. Gleevec® PKwill be assessed after oral administration of 400 mg Gleevec® alone, and after oral administration of 400 mg Gleevec® with concomitant administration of 4000 mg calcium carbonate. Two two-day/one-night inpatient stays and four brief outpatient visits are required to accommodate all study procedures.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
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. For the purposes of this protocol, "clinically significant" is defined as any history or indication of illness or disease, such as those listed above.
Body Mass Index (BMI) < 31 kg/m2 (weight/height2).
Female patients of childbearing potential must have negative pregnancy test within 14 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients 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.

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 has 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: NCT00732784

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 Centers (Hillman Cancer Center and Montefiore University Hospital locations)	Recruiting
Pittsburgh, Pennsylvania, United States

Sponsors and Collaborators

University of Pittsburgh

Novartis Pharmaceuticals

Investigators

Principal Investigator:

Jan H. Beumer, PharmD, PhD

University of Pittsburgh

More Information

No publications provided

Responsible Party:	University of Pittsburgh ( Jan H. Beumer, PharmD, PhD )
Study ID Numbers:	08-072, CSTI571BUS 280, UPCI 08-072
Study First Received:	August 7, 2008
Last Updated:	February 17, 2009
ClinicalTrials.gov Identifier:	NCT00732784 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:

Pharmacokinetics
Healthy volunteers
No condition
Pharmacokinetics study

Study placed in the following topic categories:

Imatinib
Calcium, Dietary
Antacids

Calcium Carbonate
Healthy
Protein Kinase Inhibitors

Additional relevant MeSH terms:

Imatinib
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

Antacids
Calcium Carbonate
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 07, 2009