K0706 for Patients Diagnosed With Dementia With Lewy Bodies
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|ClinicalTrials.gov Identifier: NCT03996460|
Recruitment Status : Recruiting
First Posted : June 24, 2019
Last Update Posted : October 19, 2022
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This study evaluates the safety and tolerability of treatment with K0706 in Dementia with Lewy Bodies (DLB).
The hypothesis is that K0706 will be safe and tolerable and that this drug will alter CSF and plasma biomarkers in DLB. Clinical assessments of cognitive, behavioral and motor functioning will also be evaluated. A total of 45 participants will be randomized 1:1:1 into 3 groups (n=15/per group) to be treated with sachet of 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) or sachet of 384 mg powder of K0706 (equivalent to 192 capsule of K0706) or sachet of matching placebo ( equivalent to a capsule of placebo) for 12 weeks, followed by 4-week wash-out period.
|Condition or disease||Intervention/treatment||Phase|
|Dementia With Lewy Bodies||Drug: Placebo Drug: 192 mg powder of K0706 Drug: 384 mg powder of K0706||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||The effects of 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) versus 384 mg powder of K0706 (equivalent to 192 mg capsule of K0706) versus matching placebo powder taken daily by mouth for 12 weeks, followed by a 4 week wash-out period in individuals diagnosed with DLB will be evaluated.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
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.
|Official Title:||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)|
|Actual Study Start Date :||September 5, 2019|
|Estimated Primary Completion Date :||June 2023|
|Estimated Study Completion Date :||October 2023|
Placebo Comparator: Placebo powder
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 powder orally once daily for 12 weeks (90 days).
Fifteen (15) patients in group 1 will receive the sachet of matching placebo ( equivalent to a capsule of placebo"sugar pill") orally daily for 12 weeks (90 days) without food.
Active Comparator: 192 mg powder of K0706
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 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) orally once daily for 12 weeks (90 days).
Drug: 192 mg powder of K0706
Fifteen (15) patients in group 2 will receive the sachet of 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) orally for 12 weeks (90 days) without food.
Active Comparator: 384 mg powder of K0706
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 the 384 mg powder of K0706 (equivalent to 192 mg capsule of K0706) orally once daily for 12 weeks(90 days).
Drug: 384 mg powder of K0706
Fifteen (15) patients in group 3 will receive the 384 mg powder of K0706 (equivalent to 192 capsule of K0706) orally daily for 12 weeks (90 days) without food.
- Evidence of treatment-emergent adverse effects (safety and tolerability) [ Time Frame: 12 weeks ]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).
- Measurement of K0706 concentration in plasma [ Time Frame: 12 weeks ]Concentration of K0706 will be measured in the plasma
- Measurement of K0706 concentration in CSF [ Time Frame: 12 weeks ]Concentration of K0706 will be measured in the CSF
- Measurement of Biomarker concentration in plasma [ Time Frame: 12 weeks ]Concentration of DLB related plasma biomarkers, including HVA, DOPAC, Abeta40/42, total tau, ptau231/181 and total and oligomeric alpha-synuclein will be measured.
- Measurement of Biomarker concentration in CSF [ Time Frame: 12 weeks ]Concentration of DLB related CSF biomarkers, including HVA, DOPAC, Abeta40/42, total tau, ptau231/181 and total and oligomeric alpha-synuclein will be measured.
- Measurement of the effects of K0706 on Cognition using the Montreal Cognitive Assessment (MoCA) [ Time Frame: 12 weeks ]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.
- Measurement of the effects of K0706 on Cognition using the Trail Making Test (TMT) [ Time Frame: 12 weeks ]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.
- Measuring the effects of K0706 on Cognition using the Alzheimer's Disease Assessment Scale - cognitive (ADAS-cog). [ Time Frame: 12 weeks ]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.
- Measuring the effects of K0706 on Behavior using the Alzheimer's disease Cooperative Study-Activity of Daily Living scale. [ Time Frame: 12 weeks ]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.
- Measuring the effects of K0706 on Behavior using the Neuropsychiatric Inventory (NPI) [ Time Frame: 12 weeks ]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.
- Measuring the effects of K0706 on Behavior using the Clinical Assessment of Fluctuation (CAF) [ Time Frame: 12 weeks ]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.
- Measuring the effects of K0706 on Behavior using the Irritability-Apathy Scale (IAS) [ Time Frame: 12 weeks ]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.
- Measuring the effects of K0706 on Behavior using the Problem Behaviors Assessment short form (PBA-s) [ Time Frame: 12 weeks ]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.
- Measuring the effects of K0706 on Motor Function by using the Unified Parkinson's Disease Rating Scale (UPDRS)-I-III. [ Time Frame: 12 weeks ]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.
- Measuring the effects of K0706 on Motor Function by using the Timed-Up-And-Go (TUG). [ Time Frame: 12 weeks ]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.
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|Ages Eligible for Study:||25 Years to 90 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Written informed consent
- Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative (LAR)
- Age of 25-90 years, medically stable
- Clinical diagnosis of DLB according to McKeith et al (https://www.ncbi.nlm.nih.gov/pubmed/28592453) with both dementia MoCA≥14 and Parkinsonian defined as bradykinesia in combination with rest tremor, rigidity or both UPDRS I-III ≤ 50 and UPDRS-III between 20-40.
- Dementia and Parkinsonism must be present with at least one other symptom such as fluctuation, visual hallucinations or REM sleep behavioral disorder (RBD)
- Stable on Levodopa no more than 800mg daily, acetylcholinesterase inhibitors, dopamine agonists for at least 6 weeks
- Stable on monoamine oxidase inhibitors (MOA-B) for at least 4 weeks before enrollment and during the trial
- Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI
- Corrected QT interval (QTc) 350-470 ms, inclusive
- Participants must be willing to undergo Lumbar puncture (LP) at baseline and 3 months after treatment.
- Medical history of liver or pancreatic disease, GI ulcers and Chron's disease, kidney, GI, or blood problems
- Abnormal liver function defined as Aspartate aminotransferase ( AST) and/or Alanine aminotransferase (ALT) > 100% the upper limit of the normal
- Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal or proteinuria
- History of Human immunodeficiency virus (HIV), clinically significant chronic hepatitis, or other active infection
- Hypokalemia, hypomagnesaemia, or long QT syndrome- QTc≥471 ms or concomitant drugs known to prolong the QTc interval and history of any cardiovascular disease, including myocardial infarction or cardiac failure, angina, arrhythmia
- 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.
- 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.). Should treatment with any of these agents be required, therapy with K0706 should be interrupted.
- Females must not be lactating, pregnant or with possible pregnancy
- Clinical signs indicating syndromes other than DLB including, 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
- Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or Diagnostic and Statistical Manual of Mental Disorders 4th Edition ( DSM-IV) criteria for any active major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
- 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.
- 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)
- 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.
- Must not be on any immunosuppressant medications
- Must not be enrolled as an active participant in another clinical study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03996460
|Contact: Myrna Joy J Arellano, RN||(202)-firstname.lastname@example.org|
|Contact: Sara Matar, BSemail@example.com|
|United States, District of Columbia|
|MedStar Georgetown University Hospital||Recruiting|
|Washington, District of Columbia, United States, 20007|
|Contact: Fernando L Pagan, MD 202-444-8525 firstname.lastname@example.org|
|Contact: Sara Matar, BS 202-687-7581 email@example.com|
|Principal Investigator: Fernando L Pagan, MD|
|Sub-Investigator: Charbel E Moussa, MD,PhD|
|Principal Investigator:||Fernando L Pagan, MD||Georgetown University|
|Responsible Party:||Fernando Pagan MD, Associate Professor Of Neurology , Director of Movement Disorder Program, Medical Director of NPF COE at GUH , Fellowship Director, Georgetown University|
|Other Study ID Numbers:||
|First Posted:||June 24, 2019 Key Record Dates|
|Last Update Posted:||October 19, 2022|
|Last Verified:||October 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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