Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-23

Study Completion Date

2021-08-27

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study evaluates the effect of Bosutinib (Bosulif,Pfizer®) in the treatment of patients with Dementia with Lewy Bodies. Half participants will receive 100 mg of Bosutinib , while the other half will receive placebo.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Study to Evaluate the Safety, Tolerability and Efficacy of CT1812 in Subjects With Mild to Moderate Dementia With Lewy Bodies

NCT05225415

Dementia With Lewy Bodies

COMPLETED PHASE2

A Study of LY3154207 in Participants With Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson's Disease (PD) or Dementia With Lewy Bodies (DLB)

NCT03305809

Lewy Body Dementia

COMPLETED PHASE2

K0706 for Patients Diagnosed With Dementia With Lewy Bodies

NCT03996460

Dementia With Lewy Bodies

RECRUITING PHASE2

Efficacy and Safety of the Rivastigmine Transdermal Patch in Patients With Probable Alzheimer's Disease

NCT00099242

Alzheimer's Disease Dementia, Alzheimer Type

COMPLETED PHASE3

A Safety Study of LY2886721 Single Doses in Healthy Subjects

NCT01133405

Alzheimer's Disease

COMPLETED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This proposal will evaluate the effects of Bosutinib (Bosulif, Pfizer®) treatment - an FDA-approved tyrosine kinase inhibitor that targets c-Abelson (Abl) and Src tyrosine kinases- in patients with DLB. Investigators have demonstrated safety and efficacy of this compound in pre-clinical animal models and others have shown similar benefits of Bosutinib on inflammation and neurotoxic protein clearance in neurodegeneration. Investigators have demonstrated that Bosutinib enters the brain (5% CSF:plasma ratio) and inhibits Abl at lower doses (5mg/kg) than the cancer dose (80mg/kg) in animals. Bosutinib also reduces the levels of neurotoxic proteins including alpha-synuclein, tau and beta-amyloid and improves motor and cognitive behavior in models of neurodegeneration. The use of Bosutinib is a novel strategy that promotes autophagy to clear neurotoxic protein aggregates in neurons. Bosutinib is FDA-approved for the treatment of chronic myelogenous leukemia (CML) at an oral dose of 400-600 mg daily. Based on our preclinical evidence, investigators used allometric conversion to extrapolate animal to human dose and estimated a human equivalent dose daily dose of 100mg Bosutinib in this clinical study to determine the safety and tolerability, pharmacokinetics and pharmacodynamics in patients with mild to moderate DLB.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Dementia With Lewy Bodies

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

We will evaluate the effects of 100 mg Bosutinib versus matching placebo taken daily by mouth for 12 weeks, followed by a 4 week wash-out period in individuals diagnosed with DLB. We will perform physiologically-based population pharmacokinetics (popPK) using a seamless random single dose (RSD) of Bosutinib, where participants (n=30) will be randomized to 3 groups (n=10) and take a single oral dose of 100mg, 200mg, Bosutinib or placebo (1;1;1) open label. Lumbar puncture will be performed between 1-4 hours after dosing. Participants will then be randomized double-blinded into 2 groups 1;1 using placebo(n=15) and 100mg (n=15) for 3 months.

Randomization and Registration will be performed by an internet based randomization module. Randomization of the subjects to the 2 treatment groups will be performed in a stratified manner. The chance for randomization to the groups is 1:1 for placebo: 100 mg Bosutinib.

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Participants will be randomized by a Biostatistician by an internet based randomization module into two groups. The researchers include : Primary investigator , Sub-Investigators ,Clinical Coordinators, Nurse Practitioners , and Clinical Reseach unit staff.

The investigators will be blinded to the dosage. Medications for any patient will be labeled by the CRU with a package medical identification number (Med. Id). A patient specific patient identification number (Pat. Id.) will be assigned to each patient. The investigator will have to note the Pat.Id on the designated medication package number after randomization.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Placebo

Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type DRUG

Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .

100 mg of Bosutinib

Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).

Group Type ACTIVE_COMPARATOR

Bosutinib Oral Tablet

Intervention Type DRUG

Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Placebo Oral Tablet

Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .

Intervention Type DRUG

Bosutinib Oral Tablet

Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Placebo Bosutinib(Bosulif®, SKI-606, Pfizer)

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Written informed consent
2. Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative (LAR)
3. Age of 25-90 years, medically stable
4. Clinical diagnosis of DLB according to McKeith et al (7) with both dementia MoCA≥18 and Parkinsonian defined as bradykinesia in combination with rest tremor, rigidity or both UPDRS I-III ≤ 50 and UPDRS-III between 20-40.
5. Dementia and Parkinsonism must be present with at least one other symptom such as fluctuation, visual hallucinations or REM sleep behavioral disorder (RBD)
6. Abnormal DaTScan
7. Stable on Levodopa no more than 800mg daily, acetylcholinesterase inhibitors, dopamine agonists for at least 6 weeks
8. Stable on monoamine oxidase inhibitors (MOA-B) for at least 4 weeks before enrollment
9. Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI
10. QTc interval 350-480 ms, inclusive
11. Participants must be willing to undergo LP at baseline and 3 months after treatment.

Exclusion Criteria

1. Medical history of liver or pancreatic disease, GI ulcers and Chron's disease, kidney, GI, or blood problems
2. Abnormal liver function defined as AST and/or ALT \> 100% the upper limit of the normal
3. Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal or proteinuria
4. History of HIV, clinically significant chronic hepatitis, or other active infection
5. hypokalemia, hypomagnesaemia, or long QT syndrome- QTc≥480 ms or concomitant drugs known to prolong the QTc interval and history of any cardiovascular disease, including myocardial infarction or cardiac failure, angina, arrhythmia
6. History or presence of significant cardiac conditions including: cardiovascular or cerebrovascular event (e.g. myocardial infarction, unstable angina, or stroke), congestive heart failure, first, second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances, any history of Torsade de Pointes.
7. Treatment with any of the following drugs at the time of screening or the preceding 30 days, and/or planned use over the course of the trial: Treatment with Class IA or III antiarrhythmic drugs (e.g. quinidine), treatment with QT prolonging drugs (www.crediblemeds.org)- excluding SSRIs (e.g. Citalopram, Escitalopram, Paroxetine, Sertraline, Duloxetine, Trazodone, etc.), Strong CYP3A4 inhibitors (including grapefruit juice). The concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) must be avoided. Should treatment with any of these agents be required, therapy with Bosutinib should be interrupted. Anticoagulants, including Coumadin (warfarin), heparin, enoxaparin, daltiparin, xeralto, etc. St. John's Wort and the concomitant use of strong other CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) must be avoided since these agents may reduce the concentration of Bosutinib
8. Females must not be lactating, pregnant or with possible pregnancy
9. Clinical signs indicating syndromes other than DLB including, Alzheimer's Disease (AD) idiopathic PD, corticobasal degeneration, supranuclear gaze palsy, multiple system atrophy, chronic traumatic encephalopathy, signs of frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement, Babinski sign
10. Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any active major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
11. Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal or other systemic disease or laboratory abnormality.
12. Active neoplastic disease, history of cancer five years prior to screening, including breast cancer (history of skin melanoma or stable prostate cancer are not exclusionary)
13. Contraindications to LP: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets \< 100,000, use of Coumadin/warfarin, or history of a bleeding disorder.
14. Must not be on any immunosuppressant medications
15. Must not be enrolled as an active participant in another clinical study.

Minimum Eligible Age

25 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No