Phase I Study to Evaluate the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients
This study is currently recruiting participants.
Verified May 2013 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01769768
First received: January 15, 2013
Last updated: May 31, 2013
Last verified: May 2013
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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: | September 2014 |
| Estimated Primary Completion Date: | July 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: | No |
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
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, Massachusetts | |
| Massachusetts General Hospital Dana-Farber Cancer Institute | Not yet recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact 617-632-4936 | |
| Principal Investigator: Geoffrey Shapiro | |
| United States, Michigan | |
| Karmanos Cancer Institute | Not yet recruiting |
| Detroit, Michigan, United States, 48201 | |
| Contact 001 313 576 8749 | |
| Principal Investigator: Patricia M. LoRusso | |
| United States, Pennsylvania | |
| Fox Chase Cancer Center | Not yet recruiting |
| Philadelphia, Pennsylvania, United States, 19111-2497 | |
| Contact 215-728-5534 | |
| Principal Investigator: Anthony Olszanski | |
| University of Pennsylvania--Abramson Cancer Center Abramson Cancer Center | Not yet recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Contact 001 215 796 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 001 843 792 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 | Not yet 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: | May 31, 2013 |
| 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:
|
Neoplasms Warfarin Bupropion Anticoagulants Hematologic Agents Therapeutic Uses Pharmacologic Actions Antidepressive Agents, Second-Generation Antidepressive Agents |
Psychotropic Drugs Central Nervous System Agents Dopamine Uptake Inhibitors Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Neurotransmitter Uptake Inhibitors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 18, 2013