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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01769768

Collaborator

(none)

114

Enrollment

Locations

Arms

Duration (Months)

8.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor	Drug: LDE225 Drug: Wafarin Drug: Bupropion	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Apr 1, 2013

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Drug: Bupropion

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

Outcome Measures

Primary Outcome Measures

Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin [7 days]
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
PK parameter AUClast for bupropion [7 days]
Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration
PK parameter AUCinf for bupropion [7 days]
Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration
PK parameter AUCinf for S- and R-warfarin [7 days]
Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration
PK parameter Cmax for S- and R-warfarin [7 days]
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
PK parameters Cmax for bupropion [7 days]
Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration

Secondary Outcome Measures

effects of LDE225 on the pharmacodynamic activity of warfarin [7 days]
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 [28 days cycles]
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 [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)
assess the effect of LDE225 treatment on cardiac function [screening, cycle 4 and EOT]
ECGs will be performed to determine the effect of LDE on the cardiac function.
effects of LDE225 on the pharmacodynamic activity of warfarin [7 days]
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 [28 days cycles]
safety laboratory parameters
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin [28 days cycles]
adverse event reports
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin [28 days cycles]
changes in vital signs

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Results for CLDE225A2112 can be found on the Novartis Clinical Trial Results Website

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01769768

Other Study ID Numbers:

CLDE225A2112

First Posted:

Jan 17, 2013

Last Update Posted:

Dec 19, 2020

Last Verified:

Feb 1, 2017

Keywords provided by Novartis Pharmaceuticals

Adults, Hh (Hedgehog) pathway inhibitor, LDE225, Warfarin, Bupropion, advanced solid tumor, drug-drug interaction, pharmacokinetic

Additional relevant MeSH terms:

Bupropion

Study Results

No Results Posted as of Dec 19, 2020