Phase I Study to Evaluate the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients
A Phase Ib, Multi-center, Two Parallel Group, Open-label, Drug-drug Interaction Study to Assess the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients With Advanced Solid Tumors
1 other identifier
interventional
114
1 country
13
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2013
Typical duration for phase_1
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 15, 2013
CompletedFirst Posted
Study publicly available on registry
January 17, 2013
CompletedStudy Start
First participant enrolled
April 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2016
CompletedDecember 19, 2020
February 1, 2017
3.3 years
January 15, 2013
December 16, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
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
Secondary Outcomes (8)
effects of LDE225 on the pharmacodynamic activity of warfarin
7 days
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
28 days cycles
evaluate the preliminary evidence of anti-tumor activity of LDE225 in patients with advanced solid tumors
every other cycle
assess the effect of LDE225 treatment on cardiac function
screening, cycle 4 and EOT
effects of LDE225 on the pharmacodynamic activity of warfarin
7 days
- +3 more secondary outcomes
Study Arms (2)
LDE225+Warfarin
EXPERIMENTALAt least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group.
LDE225+Bupropion
EXPERIMENTALAt least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group
Interventions
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.
75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
City of Hope National Medical Center Oncology
Duarte, California, 91010, United States
University of Kansas Medical Center CBYM338B2203
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
Related Publications (1)
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.
PMID: 32736411DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 15, 2013
First Posted
January 17, 2013
Study Start
April 1, 2013
Primary Completion
August 1, 2016
Study Completion
August 1, 2016
Last Updated
December 19, 2020
Record last verified: 2017-02