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

NCT00446004 | Completed Phase 1 DMC

• 2 other identifiers: 06-074CSTI571BUS258
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Pharmacokinetics; Healthy volunteers; No condition; Pharmacokinetics study

Outcome Measures

Primary Outcomes (1)

• 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.

  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®.

Study Arms (2)

A

OTHER

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; Drug: Omeprazole

B

OTHER

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; Drug: Omeprazole

Interventions

Imatinib Mesylate 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)

Also known as: Gleevec®

A; B

Omeprazole 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)

Also known as: Prilosec®, Proton Pump Inhibitor

A; B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead
• Novartis: collaborator

Study Sites (1)

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

Pittsburgh, Pennsylvania, 15232 / 15213, United States

Location

MeSH Terms

Interventions

Imatinib Mesylate; Omeprazole; Proton Pump Inhibitors

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Jan H. Beumer, PharmD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 8, 2007
• First Posted: March 12, 2007
• Study Start: April 1, 2007
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: June 22, 2016

Record last verified: 2016-06

Locations

US (1)