Phase I Study to Evaluate the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients
- Registration Number
- NCT01769768
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 114
- Adults
- Patients with cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor which has progressed despite standard therapy, or for which no standard therapy exists or patients with locally advanced or metastatic basal cell carcinoma who are not amendable or eligible for standard therapy.
- Protocol-defined renal , liver and bone marrow function
- CNS (Central Nervous System) tumors as well as history of brain metastases
- Systemic anticancer treatment (including biologic therapy/antibodies) within 2 weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and monoclonal antibodies).
- Radiation therapy within 4 weeks before first dose
- Investigational agents within 4 weeks before start of study therapy
- Patients with known allergy/hypersensitivity to warfarin or bupropion and/or related compounds
- Patients with a history of/or active bleeding disorders
- Patients receiving treatment with vitamin K, Coumadin or other agents containing warfarin and heparin. Heparin flush to maintain patency of a central venous access device is allowed.
- Patients receiving treatment with bupropion.
- Patients who have neuromuscular disorders that are associated with elevated CK (Creatine phosphokinase) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
- Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B or C (testing is not mandatory for study entry)
- Patients currently receiving systemic corticosteroids
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LDE225+Warfarin Wafarin At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group. LDE225+Warfarin LDE225 At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group. LDE225+Bupropion LDE225 At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group LDE225+Bupropion Bupropion At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group
- Primary Outcome Measures
Name Time Method PK parameter AUClast for bupropion 7 days Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration
Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin 7 days Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
PK parameters Cmax for bupropion 7 days Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration
PK parameter AUCinf for bupropion 7 days Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration
PK parameter AUCinf for S- and R-warfarin 7 days Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration
PK parameter Cmax for S- and R-warfarin 7 days Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
- Secondary Outcome Measures
Name Time Method safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin 28 days cycles changes in vital signs
evaluate the preliminary evidence of anti-tumor activity of LDE225 in patients with advanced solid tumors every other cycle CT or MRI imaging parameters to determine the objective response rate according to RECIST 1.1 (Response Evaluation Criteria In Solid Tumors)
effects of LDE225 on the pharmacodynamic activity of warfarin 7 days PT (Prothrombin time) parameter will be assessed to evaluate the pharmacodynamic effect of warfarin.
assess the effect of LDE225 treatment on cardiac function screening, cycle 4 and EOT ECGs will be performed to determine the effect of LDE on the cardiac function.
Trial Locations
- Locations (13)
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
University of Pennsylvania--Abramson Cancer Center Abramson 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
Cancer Centers of the Carolinas SC
🇺🇸Greenville, South Carolina, United States
Utah Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University of Utah / Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Kansas Medical Center CBYM338B2203
🇺🇸Kansas City, Kansas, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.
🇺🇸Hackensack, New Jersey, United States
City of Hope National Medical Center Oncology
🇺🇸Duarte, California, United States