Explore the Synergy of Combination TKI Therapy
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 11/8/2014 |
| Start Date: | June 2014 |
| End Date: | May 2015 |
| Contact: | Guohua An, MD, PhD |
| Email: | guohuaan@cop.ufl.edu |
Explore the Synergy of Combination TKI Therapy - A Pilot Study to Evaluate the Effect of Imatinib on Dasatinib Pharmacokinetics in Healthy Volunteers
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.
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.
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.
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.
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.
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