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

Novartis

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Wafarin; Drug: Bupropion; Drug: LDE225

Study type: Interventional

Funder types: Industry

Identifiers

NCT01769768

CLDE225A2112

Details and patient eligibility

About

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.

Enrollment: 114 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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114 participants in 2 patient groups

LDE225+Warfarin

Experimental group

Description:

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

Treatment:

Drug: Wafarin

Drug: LDE225

LDE225+Bupropion

Experimental group

Description:

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

Treatment:

Drug: Bupropion

Drug: LDE225