Phase I Study to Evaluate the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01769768
• Other study ID #: CLDE225A2112
• Status: Completed
• Phase: Phase 1
• Start date: April 2013
• Est. completion date: August 2016

Study information

• Verified date: February 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Advanced Solid Tumor

Intervention

Drug:
• LDE225
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.
• Wafarin
15 mg single dose of warfarin (oral tablet) will be given to patients.
• Bupropion
75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients

Locations

Country	Name	City	State
United States	Massachusetts General Hospital Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Medical University of South Carolina Dept.of Neurosciences/MS Ctr.	Charleston	South Carolina
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope National Medical Center Oncology	Duarte	California
United States	Cancer Centers of the Carolinas SC	Greenville	South Carolina
United States	Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.	Hackensack	New Jersey
United States	University of Kansas Medical Center CBYM338B2203	Kansas City	Kansas
United States	Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock Med Ctr	Lebanon	New Hampshire
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
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	University of Utah / Huntsman Cancer Institute	Salt Lake City	Utah
United States	Utah Health Science Center at San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin	Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration	7 days
Primary	PK parameter AUClast for bupropion	Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration	7 days
Primary	PK parameter AUCinf for bupropion	Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration	7 days
Primary	PK parameter AUCinf for S- and R-warfarin	Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration	7 days
Primary	PK parameter Cmax for S- and R-warfarin	Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration	7 days
Primary	PK parameters Cmax for bupropion	Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration	7 days
Secondary	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
Secondary	safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin	safety laboratory parameters, adverse event reports, changes in vital signs, changes in physical examination parameters	28 days cycles
Secondary	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
Secondary	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
Secondary	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
Secondary	safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin	safety laboratory parameters	28 days cycles
Secondary	safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin	adverse event reports	28 days cycles
Secondary	safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin	changes in vital signs	28 days cycles

External Links

•   Results for CLDE225A2112 can be found on the Novartis Clinical Trial Results Website