Explore the Synergy of Combination TKI Therapy

NCT02129166 | Withdrawn Phase 1

• 1 other identifier: IRB201400056
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Area under the plasma concentration versus time curve (AUC) of dasatinib

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 15, and 24 hours post-dose

Study Arms (2)

Dasatinib

PLACEBO COMPARATOR

In this group, subjects will take dasatinib only. Dose regimen: dasatinib 20 mg single oral dose

Drug: Dasatinib

Dasatinib+Imatinib

ACTIVE COMPARATOR

In this group, subjects will take imatinib prior to dasatinib administration. Dose regimen: Imatinib: 400 mg single oral dose Dasatinib: 20 mg single oral dose

Drug: Dasatinib+Imatinib

Interventions

Dasatinib DRUG

In this group, subjects will take dasatinib only. Dose regimen: dasatinib 20 mg single oral dose

Also known as: Sprycel

Dasatinib

Dasatinib+Imatinib DRUG

In this group, subjects will take imatinib prior to dasatinib administration. Dose regimen: Imatinib: 400 mg single oral dose Dasatinib: 20 mg single oral dose

Also known as: Other names of Dasatinib: Sprycel, Other names of Imatinib: Gleevec

Dasatinib+Imatinib

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead

MeSH Terms

Interventions

Dasatinib

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Guohua An, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2014
• First Posted: May 2, 2014
• Study Start: September 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 6, 2014

Record last verified: 2014-10