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

December 16, 2020 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
114

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center Oncology
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center CBYM338B2203
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Dana-Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock Med Ctr
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania--Abramson Cancer Center Abramson Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute UPMC Cancer Pavilion
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina Dept.of Neurosciences/MS Ctr.
      • Greenville, South Carolina, United States, 29605
        • Cancer Centers of the Carolinas SC
    • Texas
      • San Antonio, Texas, United States, 78229
        • Utah Health Science Center at San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah / Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LDE225+Warfarin
At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group.
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.
Drug: Wafarin
15 mg single dose of warfarin (oral tablet) will be given to patients.
Experimental: LDE225+Bupropion
At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group
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.
Drug: Bupropion
75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin
Time Frame: 7 days
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
7 days
PK parameter AUClast for bupropion
Time Frame: 7 days
Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration
7 days
PK parameter AUCinf for bupropion
Time Frame: 7 days
Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration
7 days
PK parameter AUCinf for S- and R-warfarin
Time Frame: 7 days
Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration
7 days
PK parameter Cmax for S- and R-warfarin
Time Frame: 7 days
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
7 days
PK parameters Cmax for bupropion
Time Frame: 7 days
Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration
7 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
effects of LDE225 on the pharmacodynamic activity of warfarin
Time Frame: 7 days
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
Time Frame: 28 days cycles
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
Time Frame: 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)
every other cycle
assess the effect of LDE225 treatment on cardiac function
Time Frame: screening, cycle 4 and EOT
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
Time Frame: 7 days
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
Time Frame: 28 days cycles
safety laboratory parameters
28 days cycles
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
Time Frame: 28 days cycles
adverse event reports
28 days cycles
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
Time Frame: 28 days cycles
changes in vital signs
28 days cycles

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 17, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 19, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLDE225A2112

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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