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Completed

NCT Number: NCT01769768

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

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.

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Key information

Conditions

Advanced Solid Tumor

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

City of Hope National Medical Center Oncology, Duarte, California, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

LDE225

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

Drug

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

bupropion

Drug

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

Primary outcomes

  1. Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin

    Time frame: 7 days

    Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration

  2. PK parameter AUClast for bupropion

    Time frame: 7 days

    Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration

  3. PK parameter AUCinf for bupropion

    Time frame: 7 days

    Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration

  4. PK parameter AUCinf for S- and R-warfarin

    Time frame: 7 days

    Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration

  5. PK parameter Cmax for S- and R-warfarin

    Time frame: 7 days

    Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration

  6. PK parameters Cmax for bupropion

    Time frame: 7 days

    Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration

Secondary outcomes

  1. 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.

  2. 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

  3. 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)

  4. 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.

  5. 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.

  6. safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin

    Time frame: 28 days cycles

    safety laboratory parameters

  7. safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin

    Time frame: 28 days cycles

    adverse event reports

  8. safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin

    Time frame: 28 days cycles

    changes in vital signs

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2016
Study completion
2016
First posted
Jan 17, 2013
Registry last updated
Dec 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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