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Explore the Synergy of Combination TKI Therapy

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ClinicalTrials.gov Identifier: NCT02129166
Recruitment Status : Withdrawn (PI resigned)
First Posted : May 2, 2014
Last Update Posted : October 6, 2014
Sponsor:
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE April 30, 2014
First Posted Date  ICMJE May 2, 2014
Last Update Posted Date October 6, 2014
Study Start Date  ICMJE September 2014
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2014)
Area under the plasma concentration versus time curve (AUC) of dasatinib [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 15, and 24 hours post-dose ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02129166 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Explore the Synergy of Combination TKI Therapy
Official Title  ICMJE Explore the Synergy of Combination TKI Therapy - A Pilot Study to Evaluate the Effect of Imatinib on Dasatinib Pharmacokinetics in Healthy Volunteers
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.
Detailed Description

If the subjects qualify to take part in this research study, they will undergo the following procedures.

Subjects will be asked to abstain from alcoholic beverages (24 hours), grapefruit products, herbal supplements/teas, and over-the-counter medications (48 hours) prior to the study visits. There will be two study periods in this study. During each period all the subjects are outpatients and there will be no overnight stay. During each study period, the subjects will come to the University of Florida Clinical Research Center (UF CRC) three times: on Day -1, Day 1, and Day 2, respectively. Subjects will report to the UF CRC the day before Day 1 (i.e. Day -1) to have clinical lab test and urine pregnancy test (female only). Subjects will come to UF CRC at 6:30 a.m. on Day 1 and Day 2 of each study visit. During the morning of each study period (around 8:30 am) subjects will be randomly assigned to receive a single oral dose of dasatinib 20 mg either with or without a single oral dose of imatinib 400 mg administered one hour prior to dasatinib. After the first study visit, the subjects will return one to two weeks later for the second study visit, receiving the opposite treatment. The treatment order for the study visits will be assigned randomly. The end point measures for this study are plasma concentrations of dasatinib. A total of twelve (12) blood samples will be collected for a total amount of 84 ml (about 3 ounces or about 6 tablespoonsful) for each subject during each study period.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy Volunteers
Intervention  ICMJE
  • Drug: Dasatinib
    In this group, subjects will take dasatinib only. Dose regimen: dasatinib 20 mg single oral dose
    Other Name: Sprycel
  • Drug: Dasatinib+Imatinib

    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

    Other Names:
    • Other names of Dasatinib: Sprycel
    • Other names of Imatinib: Gleevec
Study Arms  ICMJE
  • Placebo Comparator: Dasatinib
    In this group, subjects will take dasatinib only. Dose regimen: dasatinib 20 mg single oral dose
    Intervention: Drug: Dasatinib
  • Active Comparator: Dasatinib+Imatinib

    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

    Intervention: Drug: Dasatinib+Imatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 3, 2014)
0
Original Estimated Enrollment  ICMJE
 (submitted: April 30, 2014)
16
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT02129166
Other Study ID Numbers  ICMJE IRB201400056
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Guohua An, MD, PhD University of Florida
PRS Account University of Florida
Verification Date October 2014

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