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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01769768
First received: January 15, 2013
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

This is a multi center, open-label study to study the drug-drug interaction of LDE225 on the PK of warfarin and bupropion in patients with advanced solid tumors. Subjects will receive 800mg daily of LDE225 and two separate doses of either bupropion or warfarin.


Condition Intervention Phase
Advanced Solid Tumor
Drug: LDE225
Drug: Wafarin
Drug: Bupropion
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration

  • PK parameter AUClast for bupropion [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration

  • PK parameter AUCinf for bupropion [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration

  • PK parameter AUCinf for S- and R-warfarin [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration

  • PK parameter Cmax for S- and R-warfarin [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration

  • PK parameters Cmax for bupropion [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration


Secondary Outcome Measures:
  • effects of LDE225 on the pharmacodynamic activity of warfarin [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    INR parameter (International Normalized Ratio) will be assessed to evaluate the pharmacodynamic effect of warfarin.

  • safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin [ Time Frame: 28 days cycles ] [ Designated as safety issue: Yes ]
    safety laboratory parameters, adverse event reports, changes in vital signs, changes in physical examination parameters

  • evaluate the preliminary evidence of anti-tumor activity of LDE225 in patients with advanced solid tumors [ Time Frame: every other cycle ] [ Designated as safety issue: No ]
    CT or MRI imaging parameters to determine the objective response rate according to RECIST 1.1 (Response Evaluation Criteria In Solid Tumors)

  • assess the effect of LDE225 treatment on cardiac function [ Time Frame: screening, cycle 4 and EOT ] [ Designated as safety issue: Yes ]
    ECGs will be performed to determine the effect of LDE on the cardiac function.

  • effects of LDE225 on the pharmacodynamic activity of warfarin [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    PT (Prothrombin time) parameter will be assessed to evaluate the pharmacodynamic effect of warfarin.

  • safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin [ Time Frame: 28 days cycles ] [ Designated as safety issue: Yes ]
    safety laboratory parameters

  • safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin [ Time Frame: 28 days cycles ] [ Designated as safety issue: Yes ]
    adverse event reports

  • safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin [ Time Frame: 28 days cycles ] [ Designated as safety issue: Yes ]
    changes in vital signs


Estimated Enrollment: 60
Study Start Date: April 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Bupropion
bupropion 75 mg single dose (oral tablet, from an immediate release formulation) will be given to patients

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01769768

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Colorado
University of Colorado Onc Dept Not yet recruiting
Aurora, Colorado, United States, 80045
Contact    720-848-0664      
Principal Investigator: Karl Lewis         
United States, Kansas
Univ. of Kansas Medical Center CBYM338B2203 Not yet recruiting
Kansas City, Kansas, United States, 66160
Contact    913-588-5095      
Principal Investigator: Raymond Perez         
United States, Massachusetts
Massachusetts General Hospital Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02114
Contact    617-632-4936      
Principal Investigator: Geoffrey Shapiro         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact    313-576-8749      
Principal Investigator: Patricia M. LoRusso         
United States, New Hampshire
Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock Med Ctr Not yet recruiting
Lebanon, New Hampshire, United States, 03756
Contact    603-650-4828      
Principal Investigator: Lionel Lewis         
United States, New Jersey
Hackensack University Medical Center Dept.of HackensackUniv.MedCtr. Not yet recruiting
Hackensack, New Jersey, United States, 07601
Principal Investigator: Martin E Gutierrez         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact    215-728-5534      
Principal Investigator: Anthony Olszanski         
University of Pennsylvania--Abramson Cancer Center Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact    215-796-5159      
Principal Investigator: Ravi Amaravadi         
United States, South Carolina
Medical University of South Carolina Dept.of Neurosciences/MS Ctr. Recruiting
Charleston, South Carolina, United States, 29425
Contact    843-792-4271      
Principal Investigator: Carolyn Britten         
United States, Texas
Cancer Therapy & Research Center Recruiting
San Antonio, Texas, United States, 78229
Contact    210-616-5069      
Principal Investigator: John Sarantopoulos         
United States, Utah
University of Utah / Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact    801-581-5062      
Principal Investigator: Sunil Sharma         
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01769768     History of Changes
Other Study ID Numbers: CLDE225A2112
Study First Received: January 15, 2013
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Adults, Hh (Hedgehog) pathway inhibitor, LDE225, Warfarin, Bupropion, advanced solid tumor, drug-drug interaction, pharmacokinetic

Additional relevant MeSH terms:
Bupropion
Warfarin
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Anticoagulants
Hematologic Agents

ClinicalTrials.gov processed this record on September 29, 2014