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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LDE225+Warfarin | Experimental | At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group. |
|
| LDE225+Bupropion | Experimental | At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LDE225 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin | Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration | 7 days |
| PK parameter AUClast for bupropion | Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration | 7 days |
| PK parameter AUCinf for bupropion | Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration | 7 days |
| PK parameter AUCinf for S- and R-warfarin | Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration | 7 days |
| PK parameter Cmax for S- and R-warfarin | Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration | 7 days |
| PK parameters Cmax for bupropion | Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| effects of LDE225 on the pharmacodynamic activity of warfarin | INR parameter (International Normalized Ratio) will be assessed to evaluate the pharmacodynamic effect of warfarin. | 7 days |
| safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope National Medical Center Oncology | Duarte | California | 91010 | United States | ||
| University of Kansas Medical Center CBYM338B2203 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32736411 | Derived | Pooler DB, Ness DB, Sarantopoulos J, Squittieri N, Ravichandran S, Britten CD, Amaravadi RK, Vaishampayan U, LoRusso P, Shapiro GI, Olszanski AJ, Perez R, Gutierrez M, O'Rourke MA, Chung V, Lee JJ, Lewis LD. The effect of sonidegib (LDE225) on the pharmacokinetics of bupropion and warfarin in patients with advanced solid tumours. Br J Clin Pharmacol. 2021 Mar;87(3):1291-1302. doi: 10.1111/bcp.14508. Epub 2020 Aug 20. |
| Label | URL |
|---|---|
| Results for CLDE225A2112 can be found on the Novartis Clinical Trial Results Website | View source |
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|
| Wafarin | Drug | 15 mg single dose of warfarin (oral tablet) will be given to patients. |
|
| Bupropion | Drug | 75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients |
|
safety laboratory parameters, adverse event reports, changes in vital signs, changes in physical examination parameters |
| 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) | 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. | 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. | 7 days |
| safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin | safety laboratory parameters | 28 days cycles |
| safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin | adverse event reports | 28 days cycles |
| safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin | changes in vital signs | 28 days cycles |
| Kansas City |
| Kansas |
| 66160 |
| United States |
| Massachusetts General Hospital Dana-Farber Cancer Institute | Boston | Massachusetts | 02114 | United States |
| Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock Med Ctr | Lebanon | New Hampshire | 03756 | United States |
| Hackensack University Medical Center Dept.of HackensackUniv.MedCtr. | Hackensack | New Jersey | 07601 | United States |
| University of Pennsylvania--Abramson Cancer Center Abramson Cancer Center | Philadelphia | Pennsylvania | 19104 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111-2497 | United States |
| University of Pittsburgh Cancer Institute UPMC Cancer Pavilion | Pittsburgh | Pennsylvania | 15232 | United States |
| Medical University of South Carolina Dept.of Neurosciences/MS Ctr. | Charleston | South Carolina | 29425 | United States |
| Cancer Centers of the Carolinas SC | Greenville | South Carolina | 29605 | United States |
| Utah Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| University of Utah / Huntsman Cancer Institute | Salt Lake City | Utah | 84112 | United States |
| ID | Term |
|---|---|
| C561435 | sonidegib |
| D016642 | Bupropion |
| ID | Term |
|---|---|
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
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