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

NCT ID: NCT01769768

Last Updated: 2020-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-30

Study Completion Date

2016-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Advanced Solid Tumor

Keywords

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Adults, Hh (Hedgehog) pathway inhibitor, LDE225, Warfarin, Bupropion, advanced solid tumor, drug-drug interaction, pharmacokinetic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LDE225+Warfarin

At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group.

Group Type EXPERIMENTAL

LDE225

Intervention Type 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.

Wafarin

Intervention Type DRUG

15 mg single dose of warfarin (oral tablet) will be given to patients.

LDE225+Bupropion

At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group

Group Type EXPERIMENTAL

LDE225

Intervention Type 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.

Bupropion

Intervention Type DRUG

75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients

Interventions

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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.

Intervention Type DRUG

Wafarin

15 mg single dose of warfarin (oral tablet) will be given to patients.

Intervention Type DRUG

Bupropion

75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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City of Hope National Medical Center Oncology

Duarte, California, United States

Site Status

University of Kansas Medical Center CBYM338B2203

Kansas City, Kansas, United States

Site Status

Massachusetts General Hospital Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock Med Ctr

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.

Hackensack, New Jersey, United States

Site Status

University of Pennsylvania--Abramson Cancer Center Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute UPMC Cancer Pavilion

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina Dept.of Neurosciences/MS Ctr.

Charleston, South Carolina, United States

Site Status

Cancer Centers of the Carolinas SC

Greenville, South Carolina, United States

Site Status

Utah Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

University of Utah / Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 32736411 (View on PubMed)

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=16289

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

Other Identifiers

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CLDE225A2112

Identifier Type: -

Identifier Source: org_study_id