Advanced Solid TumorPhase 1NCT01769768
Phase I Study to Evaluate the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients
A Phase 1 study testing LDE225, Wafarin and Bupropion in people with Advanced Solid Tumor, run by Novartis Pharmaceuticals at 13 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- LDE225, Wafarin and Bupropion
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 13 sitesUnited States
- Study dates
- Apr 2013to Aug 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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 locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Massachusetts General Hospital Dana-Farber Cancer Institute
Boston, Massachusetts, 02114
Medical University of South Carolina Dept.of Neurosciences/MS Ctr.
Charleston, South Carolina, 29425
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope National Medical Center Oncology
Duarte, California, 91010
Cancer Centers of the Carolinas SC
Greenville, South Carolina, 29605
Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.
Hackensack, New Jersey, 07601
University of Kansas Medical Center CBYM338B2203
Kansas City, Kansas, 66160
Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock Med Ctr
Lebanon, New Hampshire, 03756
University of Pennsylvania--Abramson Cancer Center Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
University of Pittsburgh Cancer Institute UPMC Cancer Pavilion
Pittsburgh, Pennsylvania, 15232
University of Utah / Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Utah Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
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
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.
- Conditions
- Advanced Solid Tumor
- Being tested
- LDE225, Wafarin, Bupropion
- Keywords
- Adults, Hh (Hedgehog) pathway inhibitor, LDE225, Warfarin, Bupropion, advanced solid tumor, drug-drug interaction, pharmacokinetic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDE225Drug
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.
WafarinDrug
15 mg single dose of warfarin (oral tablet) will be given to patients.
BupropionDrug
75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients
| Study group | Role | What they receive |
|---|---|---|
| LDE225+Warfarin | Experimental | At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group. Receives: Drug: LDE225; Drug: Wafarin |
| LDE225+Bupropion | Experimental | At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group Receives: Drug: LDE225; Drug: Bupropion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
Measured: 7 days
PK parameter AUClast for bupropion
Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration
Measured: 7 days
PK parameter AUCinf for bupropion
Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration
Measured: 7 days
PK parameter AUCinf for S- and R-warfarin
Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration
Measured: 7 days
PK parameter Cmax for S- and R-warfarin
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
Measured: 7 days
PK parameters Cmax for bupropion
Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration
Measured: 7 days
Secondary outcomes (8)
effects of LDE225 on the pharmacodynamic activity of warfarin
INR parameter (International Normalized Ratio) will be assessed to evaluate the pharmacodynamic effect of warfarin.
Measured: 7 days
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
safety laboratory parameters, adverse event reports, changes in vital signs, changes in physical examination parameters
Measured: 28 days cycles
evaluate the preliminary evidence of anti-tumor activity of LDE225 in patients with advanced solid tumors
CT or MRI imaging parameters to determine the objective response rate according to RECIST 1.1 (Response Evaluation Criteria In Solid Tumors)
Measured: every other cycle
assess the effect of LDE225 treatment on cardiac function
ECGs will be performed to determine the effect of LDE on the cardiac function.
Measured: screening, cycle 4 and EOT
effects of LDE225 on the pharmacodynamic activity of warfarin
PT (Prothrombin time) parameter will be assessed to evaluate the pharmacodynamic effect of warfarin.
Measured: 7 days
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
safety laboratory parameters
Measured: 28 days cycles
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
adverse event reports
Measured: 28 days cycles
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
changes in vital signs
Measured: 28 days cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2013 (estimated)
- Study startApr 2013
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01769768
- Sponsor's protocol ID
- CLDE225A2112
- Status last verified
- Feb 2017
- First submitted
- 15 Jan 2013
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Pooler DB, Ness DB, Sarantopoulos J, Squittieri N, Ravichandran S, Britten CD, Amaravadi RK, Vaishampayan U, LoRusso P, Shapiro GI, Olszanski AJ, Perez R, Gutierrez M, O'Rourke MA, Chung V, Lee JJ, Lewis LD. The effect of sonidegib (LDE225) on the pharmacokinetics of bupropion and warfarin in patients with advanced solid tumours. Br J Clin Pharmacol. 2021 Mar;87(3):1291-1302. doi: 10.1111/bcp.14508. Epub 2020 Aug 20.
PubMed 32736411
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01769768
- Acronym / sponsor ID
- CLDE225A2112
- Conditions
- Advanced Solid Tumor
- Keywords
- Adults, Hh (Hedgehog) pathway inhibitor, LDE225, Warfarin, Bupropion, advanced solid tumor, drug-drug interaction, pharmacokinetic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2013
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 17 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LDE225+Warfarin | Experimental | Drug: LDE225, Drug: WafarinAt least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group. |
| LDE225+Bupropion | Experimental | Drug: LDE225, Drug: BupropionAt least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LDE225LDE225 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 | LDE225+Bupropion, LDE225+Warfarin |
| Wafarin15 mg single dose of warfarin (oral tablet) will be given to patients. | Drug | LDE225+Warfarin |
| Bupropion75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients | Drug | LDE225+Bupropion |
Primary outcome
Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin
Time frame: 7 days
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
PK parameter AUClast for bupropion
Time frame: 7 days
Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration
PK parameter AUCinf for bupropion
Time frame: 7 days
Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration
PK parameter AUCinf for S- and R-warfarin
Time frame: 7 days
Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration
PK parameter Cmax for S- and R-warfarin
Time frame: 7 days
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
PK parameters Cmax for bupropion
Time frame: 7 days
Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration
8 secondary outcomes
effects of LDE225 on the pharmacodynamic activity of warfarin
Time frame: 7 days
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
Time frame: 28 days cycles
evaluate the preliminary evidence of anti-tumor activity of LDE225 in patients with advanced solid tumors
Time frame: every other cycle
assess the effect of LDE225 treatment on cardiac function
Time frame: screening, cycle 4 and EOT
effects of LDE225 on the pharmacodynamic activity of warfarin
Time frame: 7 days
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
Time frame: 28 days cycles
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
Time frame: 28 days cycles
safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin
Time frame: 28 days cycles
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
- Derived from this study: PubMed 32736411Pooler DB, Ness DB, Sarantopoulos J, Squittieri N, Ravichandran S, Britten CD, Amaravadi RK, Vaishampayan U, LoRusso P, Shapiro GI, Olszanski AJ, Perez R, Gutierrez M, O'Rourke MA, Chung V, Lee JJ, Lewis LD. The effect of sonidegib (LDE225) on the pharmacokinetics of bupropion and warfarin in patients with advanced solid tumours. Br J Clin Pharmacol. 2021 Mar;87(3):1291-1302. doi: 10.1111/bcp.14508. Epub 2020 Aug 20.
- Results for CLDE225A2112 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LDE225, Wafarin and Bupropion in people with Advanced Solid Tumor, run by Novartis Pharmaceuticals at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin (time frame: 7 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01769768, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2020.