K0706 for Patients Diagnosed With Dementia With Lewy Bodies

• Status: Recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Georgetown University
• Collaborator: Sun Pharma Advanced Research Company Limited

Criteria

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 (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.

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. Stable on Levodopa no more than 800mg daily, acetylcholinesterase inhibitors, dopamine agonists for at least 6 weeks

7. Stable on monoamine oxidase inhibitors (MOA-B) for at least 4 weeks before enrollment and during the trial

8. Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI

9. Corrected QT interval (QTc) 350-470 ms, inclusive

10. Participants must be willing to undergo Lumbar puncture (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 Aspartate aminotransferase ( AST) and/or Alanine aminotransferase (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 Human immunodeficiency virus (HIV), clinically significant chronic hepatitis, or other active infection

5. 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

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.). Should treatment with any of these agents be required, therapy with K0706 should be interrupted.

8. Females must not be lactating, pregnant or with possible pregnancy

9. 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

10. 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

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.