Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies
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|ClinicalTrials.gov Identifier: NCT03888222|
Recruitment Status : Recruiting
First Posted : March 25, 2019
Last Update Posted : May 29, 2019
|Condition or disease||Intervention/treatment||Phase|
|Dementia With Lewy Bodies||Drug: Placebo Oral Tablet Drug: Bosutinib Oral Tablet||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
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.
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
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.
|Official Title:||A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies (DLB)|
|Actual Study Start Date :||April 23, 2019|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||August 2021|
Placebo Comparator: 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).
Drug: 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) .
Other Name: Placebo
Active Comparator: 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).
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) .
Other Name: Bosutinib(Bosulif®, SKI-606, Pfizer)
- Safety and tolerability Go/NoGo (25% discontinuations) will be determined based on any emergent adverse events. [ Time Frame: 3 Months ]We will determine safety and tolerability using the occurrence of adverse events (AEs) of interest, including myelosuppression, urinary, pancreatic and hepatic disorders, QTc prolongation as per Bosutinib IB.
- We will determine Bosutinib levels in CSF and plasma. [ Time Frame: 3 Months ]We 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. We predict that Bosutinib will be detected in the CSF. We will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics.
- We will determine changes in DLB related CSF and plasma biomarkers [ Time Frame: 3 Months ]Plasma biomarkers include HVA, DOPAC, Abeta40/42, total tau, ptau231/181 and total and oligomeric alpha-synuclein. We expect Bosutinib to lower the levels of CSF markers of cell death, including neuron specific enolase (NSE), S100B and phosphorylated neurofilaments. We will also examine the effects of Bosutinib on other exploratory CSF and plasma inflammatory biomarkers, including triggering receptors on myeloid cells (TREM)-2, which is a potential risk factor for neurodegeneration.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03888222
|Contact: Myrna J Arellano, RN||(202)-email@example.com|
|Contact: Sara Matar, BS||(571)-firstname.lastname@example.org|
|United States, District of Columbia|
|MedStar Georgetown University Hospital||Recruiting|
|Washington, District of Columbia, United States, 20007|
|Contact: Fernando Pagan, MD 202-444-1382 email@example.com|
|Contact: Sara Matar, BS 571-528-3575 firstname.lastname@example.org|
|Principal Investigator: Fernando L Pagan, MD|
|Sub-Investigator: Charbel E Moussa, MD,PhD|
|Principal Investigator:||Fernando L Pagan, MD||Georgetown Univeristy|