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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Oral hypromellose capsules.
Banner Sun Health Research Institute
Sun City, Arizona, United States
JEM Research Institute
Atlantis, Florida, United States
Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9
cGMP was measured in CSF samples using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantitative at 0.500 nanogram per milliliter (ng/ml). Evaluation of cGMP following dosing of E2027 was based on relative percent change from baseline.
Time frame: Baseline, Week 9
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation
A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE is continuous. Severe TEAE was defined as inability to work or to perform normal daily activity. A Serious TEAE was any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was medically important due to other reasons than the above mentioned criteria. An AE was defined as any untoward medical occurrence in a participant administered an investigational product. AE resulting in study discontinuation was defined as AE due to which the study medication was stopped.
Time frame: From first dose of study drug up to Week 16
Number of Participants With Treatment Emergent Orthostatic Hypotension
Orthostatic hypotension was defined based on the following criteria per protocol: Drop in standing systolic blood pressure (SBP) greater than or equal to (\>=) 20 millimeter of mercury (mmHg) compared to supine or drop in standing diastolic blood pressure (DBP) \>=10 mmHg compared to supine. Treatment-emergent orthostatic hypotension was defined as: if at baseline participant did not have SBP drop \>=20 mmHg and no DBP drop \>=10 mmHg, but developed one or more of these two events during post baseline visits.
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Elias Research Associates (Allied Biomedical Research Institute)
Miami, Florida, United States
Napa Research
Pompano Beach, Florida, United States
University of South Florida, Department of Psychiatry and Behavioral Neurosciences
Tampa, Florida, United States
Alzheimer's Research and Treatment Center
Wellington, Florida, United States
University of Kentucky, Dept of Neurology, Sanders Brown Center on Aging
Lexington, Kentucky, United States
Advanced Memory Research Institute of NJPC
Toms River, New Jersey, United States
Neurological Associates of Albany, PC
Albany, New York, United States
Columbia University Medical Center
New York, New York, United States
...and 4 more locations
Time frame: Week 3, Week 6, Week 9, Week 12 and Week 16
Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia
Orthostatic tachycardia was defined by the following criteria per protocol: Standing heart rate (HR) increased by greater than (\>) 30 beats/min compared to supine and absolute standing HR was \>100 beats/min. A participant was counted as treatment-emergent if orthostatic tachycardia emerged during the treatment, having been absent at baseline (pretreatment).
Time frame: From first dose of study drug up to Week 16
Number of Participants With Markedly Abnormal Laboratory Values
A laboratory value was determined to be a markedly abnormal value if the postbaseline grade increased from baseline and the post-baseline grade was greater than or equal to 2. Markedly abnormal laboratory values were based on Common Terminology Criteria for Adverse events (CTCAE) Version 5.0.
Time frame: From first dose of study drug up to Week 16
Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Abnormal ECG findings were defined as follows: corrected QT interval calculated using Fridericia's formula (QTcF) prolonged by \>60 millisecond (ms) from baseline and absolute QTcF \>450 ms; QTcF prolonged to \>500 ms; Change from baseline of PR interval \>=25 percent (%) to an absolute PR value of \>220 ms; Change from baseline of QRS interval \>=25% to an absolute QRS value of \>120 ms.
Time frame: From first dose of study drug up to Week 16
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories); is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. C-SSRS assess whether participant experience any of the following: completed suicide; suicide attempt (response of "yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). Here, number of participants with positive response ("yes") to suicidal behavior or/and Ideation, any non-suicidal self-injurious behavior was reported.
Time frame: From first dose of study drug up to Week 16
Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III)
The UPDRS scale evaluates extrapyramidal features in motor function in Parkinson's disease. It contains 33 items in 18 categories: (1) speech, (2) facial expression, (3) rigidity, (4) finger tapping, (5) hand movements, (6) supinational and pronation movements of hands, (7) toe tapping, (8) leg agility, (9) arising from chair, (10) gait, (11) freezing of gait, (12) postural stability, (13) posture, (14) body bradykinesia, (15) postural tremor of hands, (16) kinetic tremor of hands, (17) rest tremor amplitude and (18) constancy of rest tremor. Each item is scored 0 to 4, giving a total score range 0 to 132. Higher scores indicating more severe symptoms.
Time frame: Baseline, Week 12 and Week 16