Forty five (45) participants will be recruited and randomized into 3 arms (1:1:1). Fifteen (15) patients in arm 1 (group 1) will receive the matching placebo (8 x Placebo capsules) ("sugar pill") orally once daily for 12 weeks (90 days).

Forty five (45) participants will be recruited and randomized into 3 arms (1:1:1) .Fifteen (15) patients in arm 2 (group 2) will receive the 96 mg of K0706 (4 x 24 mg K0706 and 4 Placebo capsules) orally once daily for 12 weeks (90 days).

Forty five (45) participants will be recruited and randomized into 3 arms (1:1:1) .Fifteen (15) patients in arm 3 (group 3) will receive 192 mg of K0706 (8 x 24 mg K0706 capsules) orally once daily for 12 weeks(90 days).

Dementia With Lewy Bodies

Fifteen (15) patients in group 1 will receive the matching placebo ("sugar pill") eight (8) capsule orally daily for 12 weeks (90 days) without food.

Placebo oral capsule

Fifteen (15) patients in group 2 will receive the 96 mg of K0706 (4 x 24 mg of K0706) orally and four placebo capsules daily for 12 weeks (90 days) without food.

96 mg of K0706

Fifteen (15) patients in group 3 will receive the 192 mg of K0706 (8 x 24 mg of K0706) orally daily for 12 weeks (90 days) without food.

192 mg K0706

https://sites.google.com/a/georgetown.edu/moussa-lab/home3

MedStar Georgetown University Hospital

K0706 for Patients Diagnosed With Dementia With Lewy Bodies

A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of K0706 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics and Clinical Outcomes in Dementia With Lewy Bodies (DLB)

The investigators will determine safety and tolerability by using the occurrence of adverse events (AEs) of interest, including myelosuppression, urinary, pancreatic and hepatic disorders, gastrointestinal (GI), kidney disorders, Corrected QT-interval (QTc)prolongation as per SPARC Ltd Investigator Brochure (IB).

Concentration of K0706 will be measured in the plasma

Concentration of K0706 will be measured in the CSF

Concentration of DLB related plasma biomarkers, including HVA, DOPAC, Abeta40/42, total tau, ptau231/181 and total and oligomeric alpha-synuclein will be measured.

Concentration of DLB related CSF biomarkers, including HVA, DOPAC, Abeta40/42, total tau, ptau231/181 and total and oligomeric alpha-synuclein will be measured.

The MoCA is designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains, including attention and concentration, executive functions, memory, language, visuo-constructional skills, conceptual thinking, calculations and orientation. Scores range between 0 and 30 where 30 is the highest score and 0 is the lowest score.

The Trail Making Test (TMT) is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test can provide information about visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning. The time to complete the test is measured.

ADAS-cog aims to evaluate cognitive impairment in Alzheimer's disease. ADAS-cog was included in this LBD study to better capture potential changes in activities of daily living (ADL) and non-ADLs and severity of cognitive impairment. Points for errors in each task are added up and the greater the dysfunction, the greater the score.

ADCS-ADL is an activity of daily living inventory to assess functional performance. Using a structured interview format, study partners are queried as to whether participants attempted each item in the inventory during the prior 4 weeks and their level of performance. The ADCS-ADL includes some items from traditional basic ADL tests as well as instrumental (complex) activities of daily living. It is a 23 item scale that provide a total score from 0-78 with a lower score indicating greater severity.

The NPI is a multi-item instrument to assess psychopathology in Azheimer's disease based on interview with the study partner. The NPI evaluates both the frequency and severity of 10 neuropsychiatric disturbances. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1=mild, 2=moderate, 3=severe). The overall score and the score for each subscale are the product of severity and frequency.

The CAF consists of seven items of confusional behavior (falls, fluctuation, drowsiness, attention, disorganized thinking, altered level of consciousness, communication), scores for which are summed to provide a severity score for fluctuating confusion ranging from 0 to 21.

The IAS measures apathy and irritability in patients with dementia. The IAS is a 28-item self-administered questionnaire collecting information about different aspects of irritability and apathy utilizing a 0-3 scale for each item to indicate severity. Both a patient and a study partner version can be administered. The IAS will be completed separately by Subjects and Study Partners. A higher total score indicates higher severity.

PBA-s is a structured interview in which a trained interviewer rates the frequency and severity of neuropsychiatric symptoms through observation and the reporting of the Subject and Study Partner. Symptoms rated include depressed mood, suicidal ideation, anxiety, irritability, angry or aggressive behavior, apathy, perseverative thinking or behavior, obsessive-compulsive behaviors, delusional or paranoid thinking, hallucinations, and disoriented behavior. Each behavioral problem is rated for both severity and frequency on a 0-4- point scale; severity and frequency ratings are then multiplied to provide an overall score for each symptom.

UPDRS-I-III is used to follow the longitudinal course of Parkinson's disease. The UPDRS is made up of these sections: Part I: evaluation of mentation, behavior, and mood. Part II: self-evaluation of the activities of daily life (ADLs) Part III: clinician-scored monitored motor evaluation. Part IV: complications of therapy. Part V: Hoehn and Yahr staging of severity of Parkinson's disease. Part VI: Schwab and England ADL scale.

Timed Up and Go (TUG) is an assessment of mobility, balance, walking ability, and fall risk. It measures the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down.

Fernando Pagan MD

Associate Professor Of Neurology , Director of Movement Disorder Program, Medical Director of NPF COE at GUH , Fellowship Director

Georgetown University

Sun Pharma Advanced Research Company Limited

The effects of 92mg of K0706 versus 196mg of K0706 versus matching placebo taken daily by mouth for 12 weeks, followed by a 4 week wash-out period in individuals diagnosed with DLB will be evaluated.

Participants will be randomized by a Biostatistician by an internet based randomization module into three groups. The researchers include : Primary investigator , Sub-Investigators ,Clinical Coordinators, Nurse Practitioners, and Clinical Research unit (CRU) 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.

Ten (10) participants will receive an oral dose of 150mg Nilotinib once daily for 3 months (group 1). If Nilotinib 150 mg per mouth daily dose is tolerated by the 1st group of 10 participants for 3 months, another 10 participants will receive an oral dose of 300mg Nilotinib once daily (group 2) for 3 months.

Huntington Disease

10 participants will receive an oral dose of 150mg Nilotinib once daily for 3 months (group 1). If this dose is tolerated another 10 participants will receive an oral dose of 300mg Nilotinib once daily (group 2) for 3 months.

Nilotinib 150 MG

Translational Neurotherapeutics Program at Georgetown University Medical Center

Georgetown University Medical Center

Nilotinib in Huntington's Disease

An Open Label, Phase Ib Study to Evaluate the Impact of Low Doses of Nilotinib Treatment on Safety, Tolerability and Biomarkers in Huntington's Disease

will be measured using the occurrence of adverse events (AEs) and serious adverse events (SAEs) deemed to be possibly, probably, or definitely related to the study drug. AEs of interest are defined as QTc prolongation, myelosuppression, hepatotoxicity and pancreatitis as listed in Table 1. These AEs will be tracked over the course of the trial and reviewed by the data and safety monitoring board (DSMB) at scheduled meetings and in real time. SAEs and AEs are known to be related to drug use at 800mg daily in cancer. A small safety trial using lower oral daily doses of 150 mg and 300 mg Nilotinib in 12 PD patients showed one cardiac SAE over a six-month treatment period. Based on preliminary clinical data, investigator's brochure (IB) and scheduled EKGs and lab tests, SAEs and AEs will be evaluated real-time and on case-by-case basis.

Prior studies from our group showed that Nilotinib treatment increases the CSF levels of HVA, suggesting alteration of dopamine level. We will evaluate the effects of potential changes of dopamine levels on Chorea and behavioral symptoms in HD participants. We will use an adaptive study design that will allow examination of the effects of 150mg Nilotinib once daily in 10 HD participants. If participants in this group do not exhibit worsening chorea or behavioral changes, then 300mg Niloitnib will be given to a new group of 10 additional participants. These potential AEs will be tracked over the course of the trial and reviewed by the DSMB at scheduled meetings and in real time.

for a given participant will be defined as the ability of participants to remain on treatment. Overall tolerability of the drug will be defined as an acceptable number of up to 25% discontinuations.

Karen E. Anderson, MD

Director, Huntington Disease Care, Education and Research Center at MedStar Georgetown University Hospital and Georgetown University Medical Center

Ten (10) participants will receive an oral dose of 150mg Nilotinib once daily for 3 months (group 1). If this dose is tolerated another 10 participants will receive an oral dose of 300mg Nilotinib once daily (group 2) for 3 months.

We propose to perform an open label, Phase Ib, proof of concept study to evaluate the impact of low doses of Nilotinib treatment on safety, tolerability and biomarkers in participants with HD. We propose an adaptive design based on safety and tolerability of 150mg Nilotinib treatment for 3 months. We will first enroll 10 participants who will receive an oral dose of 150mg Nilotinib once daily (group 1) for 3 months. If these participants tolerate 150mg dose of Nilotinib, an additional 10 new HD participants (group 2) will be enrolled to evaluate the effects of 300 mg dose of Nilotinib for 3 months. We will then compare baseline with the effects of 3-months Nilotinib treatment within each group and between groups (1 and 2). Participants (group 1 and 2) will return for a follow up visit one month after the termination of 3-months treatment with Nilotinib and results will compared to baseline visits and end of study visits.

homovanillic acid/vėžys

K0706 for Patients Diagnosed With Dementia With Lewy Bodies

Nilotinib in Huntington's Disease

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