The primary objective of this clinical study is to determine whether the inhibition of cytochrome P450 (CYP) isozyme CYP2C8 by XL184 observed in in vitro preclinical studies translates into the potential for clinically significant drug-drug interactions in humans. The study will measure the effect of once daily dosing of XL184 on the pharmacokinetics (PK) of rosiglitazone. The PK of XL184 when combined with rosiglitazone will be evaluated as well. A specific objective of this study is to determine whether the interaction between XL184 and a drug such as rosiglitazone is sufficiently large enough to necessitate a dosage adjustment when used in combination with XL184, or whether the interaction would require additional therapeutic monitoring. Rosiglitazone, commonly known as Avandia, is a prescription medicine approved by the FDA used to treat adults with Type 2 (adult-onset or non-insulin dependent) diabetes mellitus (high blood sugar). In this study, subjects will only take 2 doses of rosiglitazone. There is no intention of therapy as a result of taking rosiglitazone in this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
one 4 mg dose as a tablet followed by a second 4 mg dose 3 weeks later
dosed with capsules daily
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Montefiore Medical Center
The Bronx, New York, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States
Pharmacokinetics of XL184 and rosiglitazone
To evaluate the effect of multiple daily doses of XL184 on single dose PK of rosiglitazone
Time frame: at weekly or twice-weekly visits for the first 4 weeks
Safety and tolerability of repeated administration of XL184
To evaluate safety and tolerability of daily oral administration of XL184 and two single doses of rosiglitazone
Time frame: at weekly or twice-weekly visits, then every 4 weeks
Pharmacokinetics of XL184 after co-administration of rosiglitazone
To evaluate the plasma PK of XL184 after a single dose of rosiglitazone
Time frame: at weekly or twice-weekly visits for 4 weeks
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