Explore the Synergy of Combination TKI Therapy

• Status: Withdrawn
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This research study is looking at how imatinib affects how dasatinib is absorbed and eliminated from the body. Both imatinib and dasatinib are in a class of medications called tyrosine kinase inhibitors (TKI) and they are used to treat certain types of leukemia (cancer that begins in the white blood cells). Both imatinib and dasatinib have been given safely in healthy volunteers. In this study investigators will evaluate the pharmacokinetics interaction between imatinib and dasatinib when they are co-administered. The hypothesis is that imatinib will increase the blood levels of dasatinib through inhibiting the drug metabolizing enzyme and efflux transporter that are involved in the dasatinib absorption and removal. This research will provide important new insight of combination TKI therapy in terms of transporter- and enzyme- mediated pharmacokinetic interactions. The research results will also help guide doctors in knowing how much of a tyrosine kinase inhibitor to give safely while reaching best effect in TKI combination therapy.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Florida
• Treatments: Dasatinib; Imatinib Mesylate

Criteria

Inclusion Criteria:

• under healthy condition

• Non-smokers (self-reported) age 18 -55 years

• Body Mass Index (BMI) between 18 to 30 kg/m2 inclusive

• Signed Informed Consent

Exclusion Criteria:

• Any evidence of renal dysfunction (estimated creatinine clearance < 80ml/min).

• Any evidence of impaired hepatic function (liver enzymes greater than two times the upper limit of normal or total bilirubin > 2.0 mg/dL).

• Taking any medications other than oral contraceptives or hormonal replacement therapy.

• Use of any known inhibitor or inducer of CYP3A or P-gp within 30 days prior to study drug administration.

• Consumption of alcohol, grapefruit, star fruit, grapefruit products or star fruit products within the 72-hour period prior to study drug administration.

• Women who are pregnant or currently breastfeeding.

• Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt of a transfusion of any blood product within 8 weeks prior to initial study drug administration.

• Known adverse effect or intolerance to imatinib or dasatinib.