A Study of E2027 in Participants With Dementia With Lewy Bodies (DLB) or Parkinson's Disease Dementia (PDD) With or Without Amyloid Copathology
Condition: Lewy Body Disease; Parkinson Disease
MeSH terms: Parkinson Disease; Dementia; Lewy Body Disease
Intervention: E2027
Intervention description: Oral hypromellose capsules.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: E2027; Amyloid Copathology; Parkinson's Disease Dementia; Dementia With Lewy Bodies

Summary:

      The purpose of study is to demonstrate the pharmacodynamic (PD) effects of E2027 on
      cerebrospinal fluid (CSF) cyclic guanosine monophosphate (cGMP) in participants with DLB and
      PDD with and without amyloid copathology after 9 weeks of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, age 50 to 85 years, inclusive at time of consent

          2. Meet criteria for probable DLB (as defined by the 4th report of the DLB Consortium) or
             meet criteria for probable PDD (as defined by the task force of the Movement Disorder
             Society).

          3. Mini-mental state examination (MMSE) greater than (>) 14 and less than (<) 26 at
             Screening Visit

          4. For DLB participants, have experienced visual hallucinations since onset of their DLB

          5. If receiving acetylcholinesterase inhibitors (AChEIs), must have been on a stable dose
             for at least 12 weeks before Screening Visit, with no plans for dose adjustment during
             the study. Treatment naive participants can be entered into the study but there should
             be no plans to initiate treatment with AChEIs from Screening to the end of the study.

          6. If receiving memantine, must have been on a stable dose for at least 12 weeks before
             Screening Visit, with no plans for dose adjustment during the study. Treatment naive
             participants can be entered into the study but there should be no plans to initiate
             treatment with memantine from Screening to the end of the study.

          7. If receiving Parkinson's disease medications, must have been on a stable dose for at
             least 4 weeks before Screening Visit, with no plans for dose adjustment during the
             study.

          8. Must have an identified caregiver or informant who is willing and able to provide
             follow up information on the participant throughout the course of the study.

          9. Provide written informed consent.

        Exclusion Criteria:

          1. Any neurological condition that may be contributing to cognitive impairment above and
             beyond those caused by the participant's DLB or PDD, including any comorbidities
             detected by clinical assessment or magnetic resonance imaging (MRI) (identification of
             amyloid copathology is not exclusionary)

          2. History of transient ischemic attacks or stroke within 12 months of Screening

          3. Modified Hachinski Ischemic Scale >4

          4. Parkinsonian (extrapyramidal) features with Hoehn and Yahr Scale (HYS) stage 4 or
             higher

          5. Any major psychiatric diagnosis, including schizophrenia, bipolar disorder and current
             major depressive disorder as per Diagnostic and Statistical Manual of Mental Disorders
             Fifth Edition

          6. Geriatric Depression Scale (GDS) score >8

          7. Severe visual or hearing impairment that may interfere with the participant study
             assessments including cognitive testing

          8. Any contraindications to lumbar puncture

          9. History of deep brain stimulation or other neurosurgical procedure for Parkinson's
             disease

         10. Has thyroid stimulating hormone (TSH) above normal range

         11. Abnormally low serum vitamin B12 levels (< the lower limit of normal [LLN]) for the
             testing laboratory

         12. Contraindications to MRI scanning

         13. Evidence of other clinically significant lesions that suggest a dementia diagnosis
             other than DLB or PDD on brain MRI at Screening

         14. Other significant pathological findings on brain MRI at Screening

         15. Hypersensitivity to E2027 or any of the excipients

         16. A prolonged corrected QT interval calculated using Fridericia's formula (QTcF) as
             demonstrated by triplicate ECG at the Screening or Baseline Visit (that is, mean value
             >450 millisecond [msec])

         17. Had symptomatic orthostatic hypotension or symptomatic orthostatic tachycardia which
             resulted in hospitalization or urgent medical review in hospital in the past 12 months
             before Screening

         18. Any other clinically significant abnormalities in vital signs, ECG and laboratory
             values that in the opinion of the investigator, require further investigation or
             treatment or that may interfere with study procedures or safety

         19. Malignant neoplasms within 3 years of Screening (except for basal or squamous cell
             carcinoma of the skin, or localized prostate cancer in male participants).
             Participants who had malignant neoplasms but who have had at least 3 years of
             documented uninterrupted remission before Screening need not be excluded.

         20. Has a "yes" answer to C-SSRS suicidal ideation Type 4 or 5, or any suicidal behavior
             assessment within 6 months before Screening, at Screening, or at the Baseline Visit,
             or has been hospitalized or treated for suicidal behavior in the past 5 years before
             Screening

         21. Known or suspected history of drug or alcohol dependency or abuse within 2 years
             before Screening, current use of recreational drugs or a positive urine drug test at
             Screening.

         22. Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal
             disease) which are not stably and adequately controlled, or which in the opinion of
             the investigator may affect the participant's safety or interfere with the study
             assessments

         23. Taking any of the prohibited medications or not meeting the requirements regarding
             stable doses of permitted medications

         24. Participation in a clinical study involving any investigational drug/device for DLB or
             PDD within 6 months before Screening or any other investigational drug/device in the 8
             weeks or 5 half-lives (whichever is longer) of the study medication before Screening
             unless it can be documented that the participant was in a placebo treatment arm

         25. Planned surgery which requires general, spinal or epidural anesthesia that will take
             place during the study.

         26. Males who have not had a successful vasectomy (confirmed azoospermia) if their female
             partners are of childbearing potential and are not willing to use a highly effective
             contraceptive method throughout the study period and for 98 days after study drug
             discontinuation. No sperm donation is allowed during the study period and for 98 days
             after study drug discontinuation.

         27. Females who are breastfeeding or pregnant at Screening or Baseline

         28. Females of childbearing potential who:

               -  Within 28 days before study entry, did not use a highly effective method of
                  contraception

               -  Do not agree to use a highly effective method of contraception throughout the
                  entire study period and for 28 days after study drug discontinuation