Lewy Body Disease, Parkinson Disease
Conditions
Keywords
E2027, Amyloid Copathology, Parkinson's Disease Dementia, Dementia With Lewy Bodies
Brief 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.
Interventions
DRUGE2027
Oral hypromellose capsules.
Sponsors
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9 | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 3, Week 6, Week 9, Week 12 and Week 16 | 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. |
| Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia | From first dose of study drug up to Week 16 | 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). |
| Number of Participants With Markedly Abnormal Laboratory Values | From first dose of study drug up to Week 16 | 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | From first dose of study drug up to Week 16 | 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. |
| Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | From first dose of study drug up to Week 16 | 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. |
| Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Baseline, Week 12 and Week 16 | 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. |
| Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | From first dose of study drug up to Week 16 | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants took part in the study at 15 investigative sites in the United States, and Canada from 25 Feb 2021 to 27 Jan 2022.
Pre-assignment details
A total of 83 participants were screened, of which 49 were screen failures and 34 participants received the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| DLB Without Amyloid Copathology Participants with DLB (without amyloid copathology) received E2027 50 mg capsules, orally, once daily up to 12 weeks. | 10 |
| DLB With Amyloid Copathology Participants with DLB (with amyloid copathology) received E2027 50 mg capsules, orally, once daily up to 12 weeks. | 11 |
| PDD Without Amyloid Copathology Participants with PDD (without amyloid copathology) received E2027 50 mg capsules, orally, once daily up to 12 weeks. | 10 |
| PDD With Amyloid Copathology Participants with PDD (with amyloid copathology) received E2027 50 mg capsules, orally, once daily up to 12 weeks. | 3 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 0 |
| Overall Study | Subject Choice | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | DLB Without Amyloid Copathology | DLB With Amyloid Copathology | PDD Without Amyloid Copathology | PDD With Amyloid Copathology | Total |
|---|---|---|---|---|---|
| Age, Continuous | 72.2 years STANDARD_DEVIATION 6.21 | 73.9 years STANDARD_DEVIATION 6.07 | 74.4 years STANDARD_DEVIATION 6.4 | 78.3 years STANDARD_DEVIATION 2.52 | 73.9 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 11 Participants | 9 Participants | 2 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 11 Participants | 9 Participants | 3 Participants | 33 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 5 Participants | 1 Participants | 13 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 5 Participants | 2 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 10 | 0 / 11 | 0 / 10 | 0 / 3 |
| other Total, other adverse events | 5 / 10 | 4 / 11 | 3 / 10 | 2 / 3 |
| serious Total, serious adverse events | 1 / 10 | 0 / 11 | 0 / 10 | 0 / 3 |
Outcome results
Primary
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
Population: Pharmacodynamic (PD) analysis set included participants who had sufficient PD data to derive at least 1 PD parameter.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DLB Without Amyloid Copathology | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9 | 230.412 Percent Change in CSF (ng/mL) | Standard Error 20.417 |
| DLB With Amyloid Copathology | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9 | 250.434 Percent Change in CSF (ng/mL) | Standard Error 17.015 |
| PDD Without Amyloid Copathology | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9 | 186.869 Percent Change in CSF (ng/mL) | Standard Error 24.374 |
| PDD With Amyloid Copathology | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9 | 362.519 Percent Change in CSF (ng/mL) | Standard Error 40.764 |
95% CI: [-77.635, 37.591]
95% CI: [-287.407, -63.893]
Secondary
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
Population: Safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post baseline safety assessment. Here number analyzed n are the participants who were evaluable for the outcome measure for given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DLB Without Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Baseline | 21.1 score on a scale | Standard Deviation 9.81 |
| DLB Without Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Change at Week 16 | 1.1 score on a scale | Standard Deviation 13.92 |
| DLB Without Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Change at Week 12 | 5.0 score on a scale | Standard Deviation 4.61 |
| DLB With Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Baseline | 24.6 score on a scale | Standard Deviation 12.33 |
| DLB With Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Change at Week 16 | 2.1 score on a scale | Standard Deviation 8.01 |
| DLB With Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Change at Week 12 | 6.5 score on a scale | Standard Deviation 7.2 |
| PDD Without Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Change at Week 12 | 2.8 score on a scale | Standard Deviation 10.67 |
| PDD Without Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Baseline | 28.9 score on a scale | Standard Deviation 12.35 |
| PDD Without Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Change at Week 16 | 4.3 score on a scale | Standard Deviation 17.01 |
| PDD With Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Baseline | 38.0 score on a scale | Standard Deviation 19 |
| PDD With Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Change at Week 16 | 2.3 score on a scale | Standard Deviation 2.31 |
| PDD With Amyloid Copathology | Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) | Change at Week 12 | -4.0 score on a scale | Standard Deviation 5.29 |
Secondary
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
Population: Safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post baseline safety assessment. Number analyzed n are the participants who were evaluable for the outcome measure for given categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DLB Without Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Potassium: Markedly Abnormal High | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Lymphocytes: Markedly Abnormal Low | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Creatinine: Markedly Abnormal High | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Lymphocytes: Markedly Abnormal Low | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Creatinine: Markedly Abnormal High | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Potassium: Markedly Abnormal High | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Creatinine: Markedly Abnormal High | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Potassium: Markedly Abnormal High | 1 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Lymphocytes: Markedly Abnormal Low | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Lymphocytes: Markedly Abnormal Low | 1 Participants |
| PDD With Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Creatinine: Markedly Abnormal High | 2 Participants |
| PDD With Amyloid Copathology | Number of Participants With Markedly Abnormal Laboratory Values | Potassium: Markedly Abnormal High | 0 Participants |
Secondary
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
Population: Safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post baseline safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DLB Without Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | QTcF prolongation by >60 ms from baseline and absolute QTcF >450 ms | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | QTcF prolonged to >500 ms | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Change from baseline of PR >= 25% to an absolute PR value of >220 msec | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Change from baseline of QRS >= 25% to an absolute QRS value of >120 msec | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | QTcF prolonged to >500 ms | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Change from baseline of PR >= 25% to an absolute PR value of >220 msec | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Change from baseline of QRS >= 25% to an absolute QRS value of >120 msec | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | QTcF prolongation by >60 ms from baseline and absolute QTcF >450 ms | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Change from baseline of PR >= 25% to an absolute PR value of >220 msec | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | QTcF prolonged to >500 ms | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Change from baseline of QRS >= 25% to an absolute QRS value of >120 msec | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | QTcF prolongation by >60 ms from baseline and absolute QTcF >450 ms | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Change from baseline of QRS >= 25% to an absolute QRS value of >120 msec | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | QTcF prolonged to >500 ms | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | QTcF prolongation by >60 ms from baseline and absolute QTcF >450 ms | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings | Change from baseline of PR >= 25% to an absolute PR value of >220 msec | 0 Participants |
Secondary
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
Population: Safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post baseline safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DLB Without Amyloid Copathology | Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia | 1 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia | 0 Participants |
Secondary
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
Population: Safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post baseline safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DLB Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active Thoughts with Plan and Intent | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual Suicidal Thoughts with Method; No Intent | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active Thoughts with Intent | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Preparatory Actions Towards Imminent Suicidal Behavior | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Completed Suicide | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior; No Intent | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Wish to Die | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual Suicidal Thoughts; Non-specific | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicide Attempt | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Preparatory Actions Towards Imminent Suicidal Behavior | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Wish to Die | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual Suicidal Thoughts with Method; No Intent | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicide Attempt | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active Thoughts with Intent | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active Thoughts with Plan and Intent | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Completed Suicide | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior; No Intent | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual Suicidal Thoughts; Non-specific | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Wish to Die | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Completed Suicide | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicide Attempt | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Preparatory Actions Towards Imminent Suicidal Behavior | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual Suicidal Thoughts; Non-specific | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual Suicidal Thoughts with Method; No Intent | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active Thoughts with Intent | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active Thoughts with Plan and Intent | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior; No Intent | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual Suicidal Thoughts; Non-specific | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Wish to Die | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious Behavior; No Intent | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active Thoughts with Plan and Intent | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Preparatory Actions Towards Imminent Suicidal Behavior | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Suicide Attempt | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual Suicidal Thoughts with Method; No Intent | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Completed Suicide | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active Thoughts with Intent | 0 Participants |
Secondary
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
Population: Safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post baseline safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DLB Without Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | TEAEs | 6 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | Serious TEAEs | 1 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | AE Leading to Discontinuation from Study | 1 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | Severe TEAEs | 1 Participants |
| DLB With Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | AE Leading to Discontinuation from Study | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | TEAEs | 4 Participants |
| DLB With Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | Severe TEAEs | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | Serious TEAEs | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | AE Leading to Discontinuation from Study | 1 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | Serious TEAEs | 0 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | TEAEs | 3 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | Severe TEAEs | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | TEAEs | 2 Participants |
| PDD With Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | Severe TEAEs | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | Serious TEAEs | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation | AE Leading to Discontinuation from Study | 0 Participants |
Secondary
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.
Time frame: Week 3, Week 6, Week 9, Week 12 and Week 16
Population: Safety analysis set included participants who received at least 1 dose of study drug and had at least 1 post baseline safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DLB Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 12 | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 6 | 0 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 16 | 1 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 9 | 2 Participants |
| DLB Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 3 | 0 Participants |
| DLB With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 9 | 1 Participants |
| DLB With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 12 | 3 Participants |
| DLB With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 16 | 3 Participants |
| DLB With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 6 | 3 Participants |
| DLB With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 3 | 1 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 9 | 1 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 3 | 1 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 6 | 1 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 12 | 2 Participants |
| PDD Without Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 16 | 1 Participants |
| PDD With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 12 | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 6 | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 3 | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 9 | 0 Participants |
| PDD With Amyloid Copathology | Number of Participants With Treatment Emergent Orthostatic Hypotension | Week 16 | 0 Participants |