Study To Evaluate the Efficacy, Safety and Tolerability of E2027 (Hereinafter Referred to as Irsenontrine) in Participants With Dementia With Lewy Bodies

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03467152
• Collaborator: (none)
• Enrollment: 326
• Locations: 74
• Arms: 2
• Actual Duration (Months): 23.4
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will be conducted to compare Irsenontrine to placebo on the cognitive endpoint of Montreal Cognitive Assessment (MoCA) and the global clinical endpoint of Clinician's Interview Based Impression of Change Plus (CIBIC-Plus) Caregiver Input in participants with dementia with Lewy bodies after 12 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Dementia With Lewy Bodies	Drug: Irsenontrine; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 326 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Placebo-Controlled, Double-Blind, Parallel-Group, Randomized, Study To Evaluate the Efficacy, Safety and Tolerability of E2027 in Subjects With Dementia With Lewy Bodies
• Actual Study Start Date: May 4, 2018
• Actual Primary Completion Date: Apr 15, 2020
• Actual Study Completion Date: Apr 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Irsenontrine Participants will be randomized to receive a 50 milligram (mg) once daily oral dose of Irsenontrine for 12 weeks.	Drug: Irsenontrine; Oral hypromellose capsules.; Other Names: E2027
Placebo Comparator: Placebo Participants will be randomized to receive a 50 mg once daily oral dose of Irsenontrine-matched placebo for 12 weeks.	Drug: Placebo; Oral hypromellose capsules.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Week 12 of Treatment [Baseline and Week 12]

   The MoCA scale is used for detecting cognitive impairment. The scores range between 0 to 30 points; a score of 26 or above was considered normal. Higher values represent a better outcome.

2. Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment [Week 12]

   Number of participants are reported categorized in grades based on the CIBIC-Plus scale. The CIBIC-Plus scale is designed to measure various domains that describe participant function: general, mental/cognitive state, behavior, and activities of daily living. It is a semi-structured global rating derived from a comprehensive interview with the participant and caregiver or informant by an independent rater who has no access to the source data or other psychometric test scores conducted post-randomization as part of the protocol. The CIBIC-Plus was a 7-point scale and scores were: 1 (marked improvement), 2 (moderate improvement), 3 (minimal improvement), 4 (no change), 5 (minimal worsening), 6 (moderate worsening), and 7 (marked worsening). Higher values represent a worse outcome.

Secondary Outcome Measures

1. Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment [Week 12]

   Number of participants are reported categorized in grades based on the CGIC-DLB scale. The CGIC-DLB scale provided an overall clinician-determined summary measure of change from the participant's clinical status that takes into account all available information from the efficacy endpoints (which include cognitive function, non-cognitive symptoms, behavior, and the impact of the symptoms on the participant's ability to function) and safety data. The (CGIC-DLB) was a 7-point scale and scores were: 1 (marked improvement), 2 (moderate improvement), 3 (minimal improvement), 4 (no change), 5 (minimal worsening), 6 (moderate worsening), and 7 (marked worsening). Higher values represent a worse outcome.

2. Mean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment [Baseline and Week 12]

   The CFI scale assessed cognitive fluctuation. It evaluates fluctuation in various domains including attention, ability to perform daily functions, orientation, verbal communication and behavior. The score was based on frequency and severity with a score range of 0 to 12. The scale also assessed the degree of caregiver or informant distress engendered by the symptoms. Higher scores indicating greater impairment.

3. Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Total Score Week 12 of Treatment [Baseline and Week 12]

   The MMSE is a 30-point scale that measured orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. The total score ranges from 0 (most impaired) to 30 (no impairment). The lower score means severe cognitive deficit and higher score indicates better function.

4. Mean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment [Baseline and Week 12]

   The NPI-12 scale assessed the frequency and severity of 12 neuropsychiatric symptoms commonly described in dementia participants: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating changes. The scale also assessed the degree of caregiver or informant distress engendered by each of the symptoms. The sum of the composite scores for the 12 domains yielded the NPI-12 total score. NPI-12 total score ranged from 0 (minimum severity) to 144 (maximum severity); higher score indicates greater neuropsychiatric disturbance.

5. Change From Baseline in NPI-4 Subscore at Week 12 [Baseline and Week 12]

   The NPI scale assesses the frequency and severity of 12 neuropsychiatric symptoms commonly described in dementia participants: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating changes. NPI-4 is the subscore covering the domains of delusions, hallucinations, apathy and depression. NPI-4 total subscore ranged from 0 to 48, with higher scores indicating a greater neuropsychiatric disturbance.

6. Change From Baseline in NPI-10 Subscore at Week 12 [Baseline and Week 12]

   The NPI-10 assessed range of behaviors seen in dementia for both frequency and severity. It is a 10 item questionnaire with the following domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/liability and aberrant motor behavior. The total score was a sum of the 10 domains, where the score of each domain was calculated as frequency (scale: 1=occasionally to 4=very frequently)*Severity (scale: 1=Mild to 3=Severe). Each domain has a maximum score of 12 and all domains were equally weighted for total score, the range for total score is 0 to 120. Higher scores indicating a greater neuropsychiatric disturbance.

7. Change From Baseline in NPI-D (Caregiver Distress) Total Score at Week 12 [Baseline and Week 12]

   The NPI-D scale assesses the frequency and severity of 12 neuropsychiatric symptoms commonly described in dementia participants: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating changes. The scale assesses the degree of caregiver distress engendered by each of the symptoms. The caregiver distress (NPI-D) is rated by caregiver based on his or her own stress on a five point scale from 0 to 5, where: 0(no distress), 1(minimal), 2(mild), 3(moderate), 4(moderately severe), 5(very severe or extreme). NPI-D total score is calculated by summing the scores of the 12 sub-scale distress scores. The NPI-D total scores ranges from 0 to 60 with higher scores indicating greater distress.

8. 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 or worsened in severity relative to baseline during treatment or within 28 days after the last dose of study drug. Severe TEAE was defined as inability to work or to perform normal daily activity. A Serious TEAE is any untoward medical occurrence that at any dose: results in death; is life threatening (that is, the participant was at immediate risk of death from the adverse event as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria. An adverse event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product.

9. Number of Participants With Orthostatic Hypotension [Week 2, Week 4, Week 6, Week 9 and Week 12]

   Orthostatic hypotension was defined as drop in standing systolic blood pressure greater than or equal to (>=) 20 Millimeter of mercury (mmHg) compared to supine, or drop in standing diastolic blood pressure >=10 mmHg compared to supine.

10. Number of Participants With Orthostatic Tachycardia [From first dose of study drug up to Week 16]

    Orthostatic tachycardia by numerical criteria was defined by the following numerical criteria: Standing heart rate (HR) increased by >30 beats/min compared to supine and absolute standing HR was >100 beats/min.

11. 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 common toxicity criteria grade increased from baseline and the post-baseline grade was greater than or equal to 2.

12. Number of Participants With Abnormal Electrocardiogram (ECG) Findings [From first dose of study drug up to Week 16]

13. 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.

14. Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) [Baseline up to 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, age 50 to 85 years, inclusive at time of consent.

• Meet criteria for probable dementia with Lewy bodies (DLB) (as defined by the 4th report of the DLB Consortium).

• Mini-Mental State Examination greater than or equal to (≥)14 and less than or equal to (≤) 26 at Screening Visit.

• Has experienced visual hallucinations during the past 4 weeks before Screening Visit.

• If receiving acetylcholinesterase inhibitors (AChEI), 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.

• 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.

• 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.

• Provide written informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, as required in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study, they will not be enrolled.

Exclusion Criteria:

• Any neurological condition that may be contributing to cognitive impairment above and beyond those caused by the participant's DLB, including any comorbidities detected by clinical assessment or magnetic resonance imaging (MRI).

• History of transient ischemic attacks or stroke within 12 months of Screening.

• Modified Hachinski Ischemic Scale greater than (>) 4.

• Parkinsonian (extrapyramidal) features with Hoehn and Yahr stage 4 intravenous or higher.

• Any major psychiatric diagnosis, including schizophrenia, bipolar disorder and current major depressive disorder as per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition.

• Geriatric Depression Scale score > 8.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Sun Health Research Institute	Sun City	Arizona	United States	85351
2	Advanced Research Center Inc	Anaheim	California	United States	92805
3	Parkinsons and Movement Disorders Institute	Fountain Valley	California	United States	92708
4	Paradigm Clinical Research Centers, Inc	San Diego	California	United States	92117
5	Syrentis Clinical Research	Santa Ana	California	United States	92705
6	New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
7	Miami Jewish Health-Clinical Research	Miami	Florida	United States	33137
8	Elias Research Associates (Allied Biomedical Research Institute)	Miami	Florida	United States	33155
9	Pharmax Research of South Florida; Elias Research Associates	Miami	Florida	United States	33175
10	Compass Research-Bioclinica	Orlando	Florida	United States	32806
11	Neurology Associates of Ormond Beach	Ormond Beach	Florida	United States	32174
12	Advanced Research Consultants, Inc.	Palm Beach Gardens	Florida	United States	33410
13	Anchor Neuroscience	Pensacola	Florida	United States	32502
14	Compass Research-Bioclinica	The Villages	Florida	United States	32162
15	Indiana University, Dept of Neurology	Indianapolis	Indiana	United States	46202
16	University of Kentucky, Dept of Neurology Sanders Brown Center on Aging	Lexington	Kentucky	United States	40504
17	University of Michigan	Ann Arbor	Michigan	United States	48106
18	Neurological Associates of Albany, PC	Albany	New York	United States	12208
19	Columbia University	New York	New York	United States	10032
20	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina	United States	27103
21	Cleveland Clinic, Lou Ruvo Center for Brain Health at Lakewood Hospital	Lakewood	Ohio	United States	44107
22	Summit Research Network (Oregon) Inc.	Portland	Oregon	United States	97210
23	New Orleans Center for Clinical Research	Knoxville	Tennessee	United States	37920
24	Kerwin Research Center, LLC	Dallas	Texas	United States	75231-4350
25	University of Virginia Adult Neurology	Charlottesville	Virginia	United States	22903
26	CHRU Nancy- CMRR de lorraine Hôpital de Brabois-Service de Gériatrie	Vandœuvre-lès-Nancy	Meurthe-et-Moselle	France	54500
27	Centre de Recherche Clinique - Viellissement-Cerveau-Fragilite (CRC-VCF), Hopital des Charpennes	Lyon	Villeurbanne	France	69100
28	Centre Memoire du CHRU de Lille	Lille		France	59037
29	Hopital Neurologique de Lyon	Lyon		France	69677
30	University Hospital de la Timone	Marseille		France	13385
31	Centre d'Investigation Clinique (CIC) Hopitaux universitaires Strasbourg HOPITAL DE HAUTEPIERRE - BATIMENT AX5	Strasbourg		France	67000
32	Eisai Trial Site #3	Berlin		Germany	12203
33	Eisai Trial Site #1	Kassel		Germany	34128
34	Eisai Trial Site #2	Westerstede		Germany	26655
35	Universita Chieti, CeSI Met	Chieti		Italy	66100
36	Clinica Neurologica Azienda Ospedaliera di Padova	Padova		Italy	35128
37	Eisai Trial Site #20	Chiba-shi	Chiba	Japan	263-0043
38	Eisai Trial Site #17	Fukuoka-shi	Fukuoka	Japan	814-0180
39	Eisai Trial Site #8	Fujioka-shi	Gunma	Japan	375-0017
40	Eisai Trial Site #12	Maebashi-shi	Gunma	Japan	371-8511
41	Eisai Trial Site #14	Miyoshi-shi	Hiroshima	Japan	728-0013
42	Eisai Trial Site #4	Otake-shi	Hiroshima	Japan	739-0651
43	Eisai Trial Site #2	Himeji-shi	Hyogo	Japan	670-0981
44	Eisai Trial Site #23	Yokohama-shi	Kanagawa	Japan	225-0013
45	Eisai Trial Site #11	Kumamoto-shi	Kumamoto	Japan	860-8556
46	Eisai Trial Site #5	Nishisonogigun	Nagasaki	Japan	851-2103
47	Eisai Trial Site #9	Nagaoka-shi	Niigata	Japan	940-2302
48	Eisai Trial Site #3	Kurashiki-shi	Okayama	Japan	710-0813
49	Eisai Trial Site #1	Naniwa-ku	Osaka	Japan	556-0017
50	Eisai Trial Site #16	Sakai-ku, Sakai-shi	Osaka	Japan	590-0018
51	Eisai Trial Site #24	Suita-shi	Osaka	Japan	565-0871
52	Eisai Trial Site #13	Suita-shi	Osaka	Japan	565-0874
53	Eisai Trial Site #6	Kanzaki-gun	Saga	Japan	842-0192
54	Eisai Trial Site #10	Bunkyo-ku	Tokyo	Japan	113-0034
55	Eisai Trial Site #22	Mitaka-shi	Tokyo	Japan	181-0013
56	Eisai Trial Site #18	Setagaya-Ku	Tokyo	Japan	158-0098
57	Eisai Trial Site #19	Yanai-shi	Yamaguchi	Japan	742-1352
58	Eisai Trial Site #25	Hiroshima		Japan	732-0066
59	Eisai Trial Site #21	Osaka		Japan	550-0012
60	Hospital Mutua de Terrassa	Terrassa	Barcelona	Spain	08221
61	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid	Spain	28222
62	Institut Internacional de Neurociències Aplicades	Barcelona		Spain	08006
63	Fundacio ACE	Barcelona		Spain	08228
64	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08235
65	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
66	Dementia Research Unit	Crowborough	East Sussex	United Kingdom	TN6 1HB
67	Memory Assessment and Research Centre, Moorgreen Hospital	Southampton	Hampshire	United Kingdom	S030 3JB
68	Clinical Research Centre (CRC)	Dundee	Scotland	United Kingdom	DD1 9SY
69	Queen Elizabeth University Hospital	Glasgow	Scotland	United Kingdom	G51 4TF
70	West London Mental Health Trust	Isleworth		United Kingdom	TW7 6FY
71	Kings College	London		United Kingdom	SE5 8AF
72	Cognition Health	London		United Kingdom	W1G 9JF
73	Manchester Mental Health and Social Care Trust	Manchester		United Kingdom	M25 3BL
74	Newcastle General Hospital	Newcastle		United Kingdom	NE45PL

Sponsors and Collaborators

• Eisai Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 3, 2020
• Statistical Analysis Plan - Apr 14, 2020

More Information

Publications

None provided.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT03467152
• Other Study ID Numbers: E2027-G000-201; 2017-003728-64
• First Posted: Mar 15, 2018
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eisai Inc.: Irsenontrine; Montreal Cognitive Assessment; Neuropsychiatric Inventory; Mini-Mental State Examination; Cognitive Fluctuation Inventory
• Additional relevant MeSH terms: Dementia; Lewy Body Disease

Study Results

Participant Flow

Recruitment Details

Participants took part in the study at 65 investigative sites in the United States, Japan, United Kingdom, France, Spain, Germany, and Italy from 04 May 2018 to 15 April 2020.

Pre-assignment Detail

A total of 326 participants were enrolled (signed informed consent form), of which 120 were screen failures and 206 were randomized, out of which 196 were treated. 6 participants were randomized at a site that was subsequently closed for serious compliance issues. The treatment arms to which these 6 participants were randomized is unknown and no data was collected for the Baseline, Outcome Measures, and Adverse Events module. These 6 participants were excluded from all analyses.

Arm/Group Title	Placebo	Irsenontrine 50 mg	Randomised, Not Treated Due to Site Closure
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.	6 participants were randomized at a site that was subsequently closed for serious compliance issues. The treatment arms to which these 6 participants were randomized is unknown and no data was collected for the Baseline, Outcome Measures, and Adverse Events module.
Period Title: Overall Study
STARTED	100	100	6
Treated	97	99	0
COMPLETED	84	89	0
NOT COMPLETED	16	11	6

Baseline Characteristics

Arm/Group Title	Placebo	Irsenontrine 50 mg	Total
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.	Total of all reporting groups
Overall Participants	97	99	196
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	73.8 (6.60)	75.3 (6.44)	74.5 (6.54)
Sex: Female, Male (Count of Participants)
Female	36 37.1%	37 37.4%	73 37.2%
Male	61 62.9%	62 62.6%	123 62.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 11.3%	17 17.2%	28 14.3%
Not Hispanic or Latino	73 75.3%	76 76.8%	149 76%
Unknown or Not Reported	13 13.4%	6 6.1%	19 9.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	33 34%	34 34.3%	67 34.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1%	1 1%	2 1%
White	48 49.5%	55 55.6%	103 52.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	15 15.5%	9 9.1%	24 12.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Week 12 of Treatment
Description	The MoCA scale is used for detecting cognitive impairment. The scores range between 0 to 30 points; a score of 26 or above was considered normal. Higher values represent a better outcome.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included the group of randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post randomization coprimary efficacy measurement. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure and number analyzed "n" are the participants who were evaluable for the outcome measure for given time points.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	92	96
Baseline	13.9 (5.40)	13.8 (5.18)
Change at Week 12	-0.6 (2.63)	-0.4 (3.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Irsenontrine 50 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6909
	Comments	Mixed Models for Repeated Measures Analysis (MMRM)
	Method	MMRM
	Comments

2. Primary Outcome

Title	Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment
Description	Number of participants are reported categorized in grades based on the CIBIC-Plus scale. The CIBIC-Plus scale is designed to measure various domains that describe participant function: general, mental/cognitive state, behavior, and activities of daily living. It is a semi-structured global rating derived from a comprehensive interview with the participant and caregiver or informant by an independent rater who has no access to the source data or other psychometric test scores conducted post-randomization as part of the protocol. The CIBIC-Plus was a 7-point scale and scores were: 1 (marked improvement), 2 (moderate improvement), 3 (minimal improvement), 4 (no change), 5 (minimal worsening), 6 (moderate worsening), and 7 (marked worsening). Higher values represent a worse outcome.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included the group of randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post randomization coprimary efficacy measurement. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	86	89
Marked improvement	0 0%	0 0%
Moderate improvement	5 5.2%	3 3%
Minimal improvement	13 13.4%	18 18.2%
No change	32 33%	32 32.3%
Minimal worsening	30 30.9%	28 28.3%
Moderate worsening	6 6.2%	8 8.1%
Marked worsening	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Irsenontrine 50 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8251
	Comments	Generalized Linear Mixed Models Analysis (GLMM)
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.018
	Confidence Interval	(2-Sided) 95%; 0.695 to 1.492
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment
Description	Number of participants are reported categorized in grades based on the CGIC-DLB scale. The CGIC-DLB scale provided an overall clinician-determined summary measure of change from the participant's clinical status that takes into account all available information from the efficacy endpoints (which include cognitive function, non-cognitive symptoms, behavior, and the impact of the symptoms on the participant's ability to function) and safety data. The (CGIC-DLB) was a 7-point scale and scores were: 1 (marked improvement), 2 (moderate improvement), 3 (minimal improvement), 4 (no change), 5 (minimal worsening), 6 (moderate worsening), and 7 (marked worsening). Higher values represent a worse outcome.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included the group of randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post randomization coprimary efficacy measurement. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	83	90
Marked improvement	1 1%	0 0%
Moderate improvement	3 3.1%	10 10.1%
Minimal improvement	20 20.6%	15 15.2%
No change	36 37.1%	30 30.3%
Minimal worsening	22 22.7%	27 27.3%
Moderate worsening	1 1%	8 8.1%
Marked worsening	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Irsenontrine 50 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3003
	Comments	Generalized Linear Mixed Models Analysis (GLMM)
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.853
	Confidence Interval	(2-Sided) 95%; 0.584 to 1.247
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment
Description	The CFI scale assessed cognitive fluctuation. It evaluates fluctuation in various domains including attention, ability to perform daily functions, orientation, verbal communication and behavior. The score was based on frequency and severity with a score range of 0 to 12. The scale also assessed the degree of caregiver or informant distress engendered by the symptoms. Higher scores indicating greater impairment.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included the group of randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post randomization coprimary efficacy measurement. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure and number analyzed "n" are the participants who were evaluable for the outcome measure for given time points.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	92	96
Baseline	3.4 (2.68)	3.1 (2.48)
Change at Week 12	0.1 (3.20)	0.3 (3.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Irsenontrine 50 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9198
	Comments	Mixed Models for Repeated Measures Analysis (MMRM)
	Method	MMRM
	Comments

5. Secondary Outcome

Title	Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Total Score Week 12 of Treatment
Description	The MMSE is a 30-point scale that measured orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. The total score ranges from 0 (most impaired) to 30 (no impairment). The lower score means severe cognitive deficit and higher score indicates better function.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included the group of randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post randomization coprimary efficacy measurement. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure and number analyzed "n" are the participants who were evaluable for the outcome measure for given time points.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	93	96
Baseline	21.0 (3.63)	21.1 (3.22)
Change at Week 12	-1.1 (3.63)	-1.7 (3.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Irsenontrine 50 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2909
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Mean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment
Description	The NPI-12 scale assessed the frequency and severity of 12 neuropsychiatric symptoms commonly described in dementia participants: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating changes. The scale also assessed the degree of caregiver or informant distress engendered by each of the symptoms. The sum of the composite scores for the 12 domains yielded the NPI-12 total score. NPI-12 total score ranged from 0 (minimum severity) to 144 (maximum severity); higher score indicates greater neuropsychiatric disturbance.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included the group of randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post randomization coprimary efficacy measurement. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure and number analyzed "n" are the participants who were evaluable for the outcome measure for given time points.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	93	96
Baseline	17.6 (14.32)	19.1 (16.07)
Change at Week 12	-0.2 (11.07)	-2.0 (15.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Irsenontrine 50 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6127
	Comments	Mixed Models for Repeated Measures Analysis (MMRM)
	Method	MMRM
	Comments

7. Secondary Outcome

Title	Change From Baseline in NPI-4 Subscore at Week 12
Description	The NPI scale assesses the frequency and severity of 12 neuropsychiatric symptoms commonly described in dementia participants: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating changes. NPI-4 is the subscore covering the domains of delusions, hallucinations, apathy and depression. NPI-4 total subscore ranged from 0 to 48, with higher scores indicating a greater neuropsychiatric disturbance.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included the group of randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post randomization coprimary efficacy measurement. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure and number analyzed "n" are the participants who were evaluable for the outcome measure for given time points.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	93	96
Baseline	8.2 (6.40)	8.6 (7.18)
Change at Week 12	-0.4 (5.15)	-0.6 (6.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Irsenontrine 50 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8780
	Comments	Mixed Models for Repeated Measures Analysis (MMRM)
	Method	MMRM
	Comments

8. Secondary Outcome

Title	Change From Baseline in NPI-10 Subscore at Week 12
Description	The NPI-10 assessed range of behaviors seen in dementia for both frequency and severity. It is a 10 item questionnaire with the following domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/liability and aberrant motor behavior. The total score was a sum of the 10 domains, where the score of each domain was calculated as frequency (scale: 1=occasionally to 4=very frequently)*Severity (scale: 1=Mild to 3=Severe). Each domain has a maximum score of 12 and all domains were equally weighted for total score, the range for total score is 0 to 120. Higher scores indicating a greater neuropsychiatric disturbance.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included the group of randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post randomization coprimary efficacy measurement. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure and number analyzed "n" are the participants who were evaluable for the outcome measure for given time points.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	93	96
Baseline	13.5 (11.22)	14.9 (13.54)
Change at Week 12	0.6 (9.32)	-1.4 (12.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Irsenontrine 50 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4090
	Comments	Mixed Models for Repeated Measures Analysis (MMRM)
	Method	MMRM
	Comments

9. Secondary Outcome

Title	Change From Baseline in NPI-D (Caregiver Distress) Total Score at Week 12
Description	The NPI-D scale assesses the frequency and severity of 12 neuropsychiatric symptoms commonly described in dementia participants: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating changes. The scale assesses the degree of caregiver distress engendered by each of the symptoms. The caregiver distress (NPI-D) is rated by caregiver based on his or her own stress on a five point scale from 0 to 5, where: 0(no distress), 1(minimal), 2(mild), 3(moderate), 4(moderately severe), 5(very severe or extreme). NPI-D total score is calculated by summing the scores of the 12 sub-scale distress scores. The NPI-D total scores ranges from 0 to 60 with higher scores indicating greater distress.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included the group of randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post randomization coprimary efficacy measurement. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure and number analyzed "n" are the participants who were evaluable for the outcome measure for given time points.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	93	96
Baseline	8.8 (7.65)	9.4 (8.44)
Change at Week 12	-0.2 (6.18)	-0.6 (7.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Irsenontrine 50 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8736
	Comments	Mixed Models for Repeated Measures Analysis (MMRM)
	Method	MMRM
	Comments

10. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation
Description	A TEAE was defined as an AE that emerged or worsened in severity relative to baseline during treatment or within 28 days after the last dose of study drug. Severe TEAE was defined as inability to work or to perform normal daily activity. A Serious TEAE is any untoward medical occurrence that at any dose: results in death; is life threatening (that is, the participant was at immediate risk of death from the adverse event as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria. An adverse event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product.
Time Frame	From first dose of study drug up to Week 16

Outcome Measure Data

Analysis Population Description

The safety analysis set included the group of participants who received at least 1 dose of study drug and had at least 1 post randomization safety assessment.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	97	99
TEAEs	67 69.1%	70 70.7%
Severe TEAEs	6 6.2%	2 2%
Serious TEAEs	9 9.3%	7 7.1%
AE Leading to Discontinuation from Study	7 7.2%	6 6.1%

11. Secondary Outcome

Title	Number of Participants With Orthostatic Hypotension
Description	Orthostatic hypotension was defined as drop in standing systolic blood pressure greater than or equal to (>=) 20 Millimeter of mercury (mmHg) compared to supine, or drop in standing diastolic blood pressure >=10 mmHg compared to supine.
Time Frame	Week 2, Week 4, Week 6, Week 9 and Week 12

Outcome Measure Data

Analysis Population Description

The safety analysis set included the group of participants who received at least 1 dose of study drug and had at least 1 post randomization safety assessment.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	97	99
Week 2	10 10.3%	2 2%
Week 4	9 9.3%	7 7.1%
Week 6	6 6.2%	11 11.1%
Week 9	13 13.4%	9 9.1%
Week 12	7 7.2%	9 9.1%

12. Secondary Outcome

Title	Number of Participants With Orthostatic Tachycardia
Description	Orthostatic tachycardia by numerical criteria was defined by the following numerical criteria: Standing heart rate (HR) increased by >30 beats/min compared to supine and absolute standing HR was >100 beats/min.
Time Frame	From first dose of study drug up to Week 16

Outcome Measure Data

Analysis Population Description

The safety analysis set included the group of participants who received at least 1 dose of study drug and had at least 1 post randomization safety assessment.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	97	99
Count of Participants [Participants]	1 1%	0 0%

13. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Laboratory Values
Description	A laboratory value was determined to be a markedly abnormal value if the postbaseline common toxicity criteria grade increased from baseline and the post-baseline grade was greater than or equal to 2.
Time Frame	From first dose of study drug up to Week 16

Outcome Measure Data

Analysis Population Description

The safety analysis set included the group of participants who received at least 1 dose of study drug and had at least 1 post randomization safety assessment. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure. Number analyzed "n" are the participants who were evaluable for the outcome measure for given categories.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	94	97
Albumin: Markedly Abnormal Low	1 1%	0 0%
Bilirubin: Markedly Abnormal High	1 1%	0 0%
Calcium: Markedly Abnormal Low	1 1%	0 0%
Creatinine: Markedly Abnormal High	0 0%	2 2%
Gamma Glutamyl Transferase: Markedly Abnormal High	2 2.1%	0 0%
Hemoglobin: Markedly Abnormal Low	0 0%	1 1%
Leukocytes: Markedly Abnormal Low	0 0%	1 1%
Lymphocytes: Markedly Abnormal Low	4 4.1%	1 1%
Neutrophils: Markedly Abnormal Low	1 1%	1 1%
Phosphate: Markedly Abnormal Low	0 0%	1 1%
Potassium: Markedly Abnormal Low	1 1%	0 0%
Potassium: Markedly Abnormal High	2 2.1%	0 0%

14. Secondary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time Frame	From first dose of study drug up to Week 16

Outcome Measure Data

Analysis Population Description

The safety analysis set included the group of participants who received at least 1 dose of study drug and had at least 1 post randomization safety assessment. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	96	98
QTcF prolongation by >60 milliseconds (ms) from baseline and absolute QTcF >450 ms	2 2.1%	0 0%
QTcF prolongation to >500 ms	2 2.1%	0 0%
Change from baseline of PR >= 25 percent (%) to an absolute PR value of >220 msec	1 1%	1 1%
Change from baseline of QRS >= 25% to an absolute QRS value of >120 msec	1 1%	0 0%

15. Secondary Outcome

Title	Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)
Description	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

Outcome Measure Data

Analysis Population Description

The safety analysis set included the group of participants who received at least 1 dose of study drug and had at least 1 post randomization safety assessment. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	95	98
Completed Suicide	0 0%	0 0%
Suicide Attempt	0 0%	0 0%
Preparatory Actions Towards Imminent Suicidal Behavior	0 0%	2 2%
Wish to Die	6 6.2%	8 8.1%
Actual Suicidal Thoughts; Non-specific	1 1%	1 1%
Actual Suicidal Thoughts with Method; No Intent	0 0%	1 1%
Active Thoughts with Intent	0 0%	0 0%
Active Thoughts with Plan and Intent	0 0%	0 0%
Self-injurious Behavior; No Intent	0 0%	0 0%

16. Secondary Outcome

Title	Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III)
Description	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 up to Week 16

Outcome Measure Data

Analysis Population Description

The safety analysis set included the group of participants who received at least 1 dose of study drug and had at least 1 post randomization safety assessment. Here number analyzed "n" are the participants who were evaluable for the outcome measure for given time points.

Arm/Group Title	Placebo	Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Measure Participants	97	99
Baseline	31.3 (18.51)	34.5 (18.12)
Change at Week 16	-1.2 (10.97)	1.0 (9.22)

Adverse Events

Time Frame	From first dose of study drug up to follow up (Week 16)
Arm/Group Title	Placebo		Irsenontrine 50 mg
Arm/Group Description	Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.		Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
All Cause Mortality
	Placebo		Irsenontrine 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/97 (1%)		0/99 (0%)
Serious Adverse Events
	Placebo		Irsenontrine 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/97 (9.3%)		7/99 (7.1%)
Gastrointestinal disorders
Constipation	0/97 (0%)	0	1/99 (1%)	1
Ileal perforation	1/97 (1%)	1	0/99 (0%)	0
Infections and infestations
Influenza	1/97 (1%)	1	0/99 (0%)	0
Peritonitis	1/97 (1%)	1	0/99 (0%)	0
Pneumonia	1/97 (1%)	1	0/99 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	1/97 (1%)	1	0/99 (0%)	0
Femur fracture	1/97 (1%)	1	0/99 (0%)	0
Ligament sprain	1/97 (1%)	1	0/99 (0%)	0
Periprosthetic fracture	0/97 (0%)	0	1/99 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/97 (1%)	1	0/99 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/97 (1%)	1	0/99 (0%)	0
Dementia with Lewy bodies	1/97 (1%)	1	2/99 (2%)	2
Psychiatric disorders
Aggression	0/97 (0%)	0	1/99 (1%)	1
Delirium	0/97 (0%)	0	1/99 (1%)	1
Respiratory, thoracic and mediastinal disorders
Haemoptysis	0/97 (0%)	0	1/99 (1%)	2
Pneumonia aspiration	0/97 (0%)	0	1/99 (1%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/97 (0%)	0	1/99 (1%)	1
Vascular disorders
Hypotension	0/97 (0%)	0	1/99 (1%)	1
Orthostatic hypotension	1/97 (1%)	1	0/99 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Irsenontrine 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/97 (67%)		68/99 (68.7%)
Blood and lymphatic system disorders
Blood loss anaemia	1/97 (1%)	1	0/99 (0%)	0
Disseminated intravascular coagulation	0/97 (0%)	0	1/99 (1%)	1
Lymphopenia	1/97 (1%)	1	0/99 (0%)	0
Neutropenia	1/97 (1%)	1	0/99 (0%)	0
Cardiac disorders
Atrial fibrillation	2/97 (2.1%)	2	0/99 (0%)	0
Palpitations	0/97 (0%)	0	1/99 (1%)	1
Ear and labyrinth disorders
Ear haemorrhage	0/97 (0%)	0	1/99 (1%)	1
Eye disorders
Cataract	1/97 (1%)	1	0/99 (0%)	0
Dry eye	0/97 (0%)	0	1/99 (1%)	1
Eye discharge	0/97 (0%)	0	1/99 (1%)	1
Lacrimation increased	1/97 (1%)	1	0/99 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	1/97 (1%)	1	0/99 (0%)	0
Anal incontinence	2/97 (2.1%)	2	0/99 (0%)	0
Constipation	4/97 (4.1%)	4	1/99 (1%)	1
Dental caries	1/97 (1%)	1	0/99 (0%)	0
Diarrhoea	3/97 (3.1%)	3	4/99 (4%)	4
Dry mouth	0/97 (0%)	0	1/99 (1%)	1
Nausea	3/97 (3.1%)	3	1/99 (1%)	1
Stomatitis	1/97 (1%)	1	0/99 (0%)	0
Vomiting	2/97 (2.1%)	2	2/99 (2%)	2
General disorders
Chest discomfort	0/97 (0%)	0	1/99 (1%)	1
Fatigue	2/97 (2.1%)	2	1/99 (1%)	1
Malaise	1/97 (1%)	1	2/99 (2%)	2
Non-cardiac chest pain	1/97 (1%)	1	0/99 (0%)	0
Oedema peripheral	2/97 (2.1%)	2	3/99 (3%)	4
Pyrexia	1/97 (1%)	1	0/99 (0%)	0
Infections and infestations
Bronchitis	2/97 (2.1%)	2	1/99 (1%)	1
Cystitis	2/97 (2.1%)	2	1/99 (1%)	1
Folliculitis	1/97 (1%)	1	0/99 (0%)	0
Gastroenteritis	1/97 (1%)	1	0/99 (0%)	0
Herpes zoster	1/97 (1%)	1	0/99 (0%)	0
Nasopharyngitis	3/97 (3.1%)	3	5/99 (5.1%)	5
Oral herpes	0/97 (0%)	0	1/99 (1%)	1
Pharyngitis	0/97 (0%)	0	1/99 (1%)	1
Pneumonia	1/97 (1%)	1	0/99 (0%)	0
Sinusitis	1/97 (1%)	1	1/99 (1%)	1
Tinea pedis	1/97 (1%)	1	0/99 (0%)	0
Tooth abscess	0/97 (0%)	0	1/99 (1%)	1
Tooth infection	0/97 (0%)	0	2/99 (2%)	3
Upper respiratory tract infection	1/97 (1%)	1	2/99 (2%)	2
Urinary tract infection	5/97 (5.2%)	5	4/99 (4%)	4
Injury, poisoning and procedural complications
Contusion	3/97 (3.1%)	4	1/99 (1%)	1
Facial bones fracture	1/97 (1%)	1	0/99 (0%)	0
Fall	15/97 (15.5%)	15	10/99 (10.1%)	14
Femur fracture	1/97 (1%)	2	0/99 (0%)	0
Foot fracture	2/97 (2.1%)	2	0/99 (0%)	0
Joint dislocation	0/97 (0%)	0	1/99 (1%)	1
Rib fracture	1/97 (1%)	1	1/99 (1%)	1
Skin abrasion	1/97 (1%)	1	0/99 (0%)	0
Skin laceration	1/97 (1%)	1	1/99 (1%)	1
Spinal compression fracture	1/97 (1%)	1	0/99 (0%)	0
Thermal burn	1/97 (1%)	1	0/99 (0%)	0
Upper limb fracture	0/97 (0%)	0	1/99 (1%)	1
Wound	1/97 (1%)	2	1/99 (1%)	1
Ligament sprain	1/97 (1%)	1	0/99 (0%)	0
Investigations
Alanine aminotransferase increased	1/97 (1%)	1	0/99 (0%)	0
Blood pressure decreased	0/97 (0%)	0	1/99 (1%)	1
Blood triglycerides increased	0/97 (0%)	0	1/99 (1%)	1
Electrocardiogram QT prolonged	2/97 (2.1%)	2	2/99 (2%)	2
Electrocardiogram T wave inversion	0/97 (0%)	0	1/99 (1%)	1
Haemoglobin decreased	1/97 (1%)	1	0/99 (0%)	0
Liver function test increased	0/97 (0%)	0	1/99 (1%)	1
Lymphocyte count decreased	1/97 (1%)	2	0/99 (0%)	0
Norovirus test positive	1/97 (1%)	1	0/99 (0%)	0
Prostatic specific antigen increased	1/97 (1%)	1	0/99 (0%)	0
Red blood cell count decreased	1/97 (1%)	1	0/99 (0%)	0
Weight decreased	1/97 (1%)	1	0/99 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/97 (0%)	0	1/99 (1%)	1
Dehydration	1/97 (1%)	1	0/99 (0%)	0
Diabetes mellitus	1/97 (1%)	1	1/99 (1%)	1
Folate deficiency	0/97 (0%)	0	1/99 (1%)	1
Hyperglycaemia	0/97 (0%)	0	2/99 (2%)	2
Hyperkalaemia	1/97 (1%)	1	0/99 (0%)	0
Hypophosphataemia	0/97 (0%)	0	1/99 (1%)	1
Vitamin D deficiency	1/97 (1%)	1	0/99 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/97 (2.1%)	2	0/99 (0%)	0
Flank pain	1/97 (1%)	1	0/99 (0%)	0
Joint range of motion decreased	1/97 (1%)	1	0/99 (0%)	0
Lumbar spinal stenosis	1/97 (1%)	1	0/99 (0%)	0
Mobility decreased	1/97 (1%)	1	0/99 (0%)	0
Muscular weakness	1/97 (1%)	1	1/99 (1%)	1
Musculoskeletal pain	0/97 (0%)	0	1/99 (1%)	1
Neck pain	1/97 (1%)	1	0/99 (0%)	0
Periarthritis	0/97 (0%)	0	1/99 (1%)	1
Polymyalgia rheumatica	0/97 (0%)	0	1/99 (1%)	1
Arthralgia	1/97 (1%)	1	1/99 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	0/97 (0%)	0	1/99 (1%)	1
Prostate cancer	1/97 (1%)	1	0/99 (0%)	0
Nervous system disorders
Cognitive disorder	1/97 (1%)	1	1/99 (1%)	1
Dementia with Lewy bodies	0/97 (0%)	0	4/99 (4%)	4
Disturbance in attention	1/97 (1%)	1	0/99 (0%)	0
Dizziness	1/97 (1%)	4	5/99 (5.1%)	5
Dizziness postural	1/97 (1%)	1	0/99 (0%)	0
Headache	1/97 (1%)	1	2/99 (2%)	2
Hypersomnia	0/97 (0%)	0	1/99 (1%)	1
Hypoaesthesia	0/97 (0%)	0	1/99 (1%)	1
Loss of consciousness	1/97 (1%)	1	1/99 (1%)	2
Nystagmus	0/97 (0%)	0	1/99 (1%)	1
Paraesthesia	1/97 (1%)	1	0/99 (0%)	0
Parkinsonism	2/97 (2.1%)	2	1/99 (1%)	1
Petit mal epilepsy	1/97 (1%)	1	0/99 (0%)	0
Restless legs syndrome	1/97 (1%)	1	0/99 (0%)	0
Somnolence	1/97 (1%)	1	3/99 (3%)	3
Syncope	0/97 (0%)	0	1/99 (1%)	1
Tremor	2/97 (2.1%)	2	1/99 (1%)	1
Visuospatial deficit	1/97 (1%)	1	0/99 (0%)	0
Psychiatric disorders
Affective disorder	0/97 (0%)	0	1/99 (1%)	1
Aggression	0/97 (0%)	0	2/99 (2%)	2
Attention deficit/hyperactivity disorder	0/97 (0%)	0	1/99 (1%)	1
Behaviour disorder	0/97 (0%)	0	2/99 (2%)	3
Confusional state	2/97 (2.1%)	2	3/99 (3%)	3
Delirium	1/97 (1%)	1	1/99 (1%)	1
Delusion	1/97 (1%)	1	0/99 (0%)	0
Depressed mood	1/97 (1%)	1	1/99 (1%)	1
Depression	2/97 (2.1%)	2	0/99 (0%)	0
Euphoric mood	0/97 (0%)	0	1/99 (1%)	1
Hallucination, auditory	0/97 (0%)	0	1/99 (1%)	1
Hallucination, visual	9/97 (9.3%)	11	7/99 (7.1%)	8
Irritability	2/97 (2.1%)	2	0/99 (0%)	0
Libido increased	0/97 (0%)	0	1/99 (1%)	1
Neuropsychiatric symptoms	0/97 (0%)	0	1/99 (1%)	1
Nightmare	1/97 (1%)	1	0/99 (0%)	0
Panic attack	1/97 (1%)	1	0/99 (0%)	0
Paranoia	2/97 (2.1%)	2	0/99 (0%)	0
Rapid eye movement sleep behaviour disorder	0/97 (0%)	0	1/99 (1%)	1
Sexually inappropriate behaviour	1/97 (1%)	1	0/99 (0%)	0
Sleep disorder	1/97 (1%)	1	0/99 (0%)	0
Suicidal ideation	2/97 (2.1%)	2	2/99 (2%)	2
Renal and urinary disorders
Acute kidney injury	1/97 (1%)	1	0/99 (0%)	0
Dysuria	1/97 (1%)	1	1/99 (1%)	1
Pollakiuria	1/97 (1%)	1	1/99 (1%)	1
Urinary incontinence	2/97 (2.1%)	2	2/99 (2%)	2
Urinary retention	1/97 (1%)	1	0/99 (0%)	0
Respiratory, thoracic and mediastinal disorders
Alveolar lung disease	0/97 (0%)	0	1/99 (1%)	1
Atelectasis	0/97 (0%)	0	2/99 (2%)	2
Cough	1/97 (1%)	1	1/99 (1%)	1
Dyspnoea	1/97 (1%)	1	1/99 (1%)	1
Oropharyngeal pain	2/97 (2.1%)	2	0/99 (0%)	0
Orthopnoea	0/97 (0%)	0	1/99 (1%)	1
Pulmonary mass	0/97 (0%)	0	1/99 (1%)	1
Rales	1/97 (1%)	1	0/99 (0%)	0
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/97 (0%)	0	2/99 (2%)	2
Dermatitis allergic	0/97 (0%)	0	1/99 (1%)	1
Dermatitis bullous	0/97 (0%)	0	1/99 (1%)	1
Eczema asteatotic	2/97 (2.1%)	2	0/99 (0%)	0
Papule	0/97 (0%)	0	1/99 (1%)	1
Pruritus	2/97 (2.1%)	2	0/99 (0%)	0
Rash macular	1/97 (1%)	1	0/99 (0%)	0
Skin lesion	0/97 (0%)	0	2/99 (2%)	4
Skin ulcer	0/97 (0%)	0	1/99 (1%)	1
Xeroderma	0/97 (0%)	0	1/99 (1%)	1
Vascular disorders
Aortic aneurysm	0/97 (0%)	0	1/99 (1%)	1
Haematoma	1/97 (1%)	1	0/99 (0%)	0
Hypertension	0/97 (0%)	0	1/99 (1%)	1
Orthostatic hypotension	0/97 (0%)	0	3/99 (3%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.