This is a multi center, open-label study to evaluate the drug-drug interaction of LDE225 on the PK of bupropion and warfarin patients with advanced solid tumors. Subjects will receive 800mg daily of LDE225 and two separate doses of either bupropion or warfarin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
114
LDE225 800 mg once daily dosing will begin on Cycle 1 Day 1 of a 28-day cycle.Treatment with LDE225 for both groups will continue until the patient experiences unacceptable toxicity that precludes further treatment, disease progression, withdrawal of consent and/or at the discretion of the investigator.
15 mg single dose of warfarin (oral tablet) will be given to patients.
75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients
City of Hope National Medical Center Oncology
Duarte, California, United States
University of Kansas Medical Center CBYM338B2203
Kansas City, Kansas, United States
Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
Time frame: 7 days
PK parameter AUClast for bupropion
Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration
Time frame: 7 days
PK parameter AUCinf for bupropion
Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration
Time frame: 7 days
PK parameter AUCinf for S- and R-warfarin
Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration
Time frame: 7 days
PK parameter Cmax for S- and R-warfarin
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
Time frame: 7 days
PK parameters Cmax for bupropion
Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration
Time frame: 7 days
effects of LDE225 on the pharmacodynamic activity of warfarin
INR parameter (International Normalized Ratio) will be assessed to evaluate the pharmacodynamic effect of warfarin.
Time frame: 7 days
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
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Massachusetts General Hospital Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock Med Ctr
Lebanon, New Hampshire, United States
Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.
Hackensack, New Jersey, United States
University of Pennsylvania--Abramson Cancer Center Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
University of Pittsburgh Cancer Institute UPMC Cancer Pavilion
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina Dept.of Neurosciences/MS Ctr.
Charleston, South Carolina, United States
...and 3 more locations
safety laboratory parameters, adverse event reports, changes in vital signs, changes in physical examination parameters
Time frame: 28 days cycles
evaluate the preliminary evidence of anti-tumor activity of LDE225 in patients with advanced solid tumors
CT or MRI imaging parameters to determine the objective response rate according to RECIST 1.1 (Response Evaluation Criteria In Solid Tumors)
Time frame: every other cycle
assess the effect of LDE225 treatment on cardiac function
ECGs will be performed to determine the effect of LDE on the cardiac function.
Time frame: screening, cycle 4 and EOT
effects of LDE225 on the pharmacodynamic activity of warfarin
PT (Prothrombin time) parameter will be assessed to evaluate the pharmacodynamic effect of warfarin.
Time frame: 7 days
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
safety laboratory parameters
Time frame: 28 days cycles
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
adverse event reports
Time frame: 28 days cycles
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
changes in vital signs
Time frame: 28 days cycles