Trial Outcomes & Findings for Study To Evaluate the Efficacy, Safety and Tolerability of E2027 (Hereinafter Referred to as Irsenontrine) in Participants With Dementia With Lewy Bodies (NCT NCT03467152)

Last Updated: 2022-08-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

326 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2022-08-01

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.	Randomised, Not Treated Due to Site Closure 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.
Overall Study STARTED	100	100	6
Overall Study Treated	97	99	0
Overall Study COMPLETED	84	89	0
Overall Study NOT COMPLETED	16	11	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.	Randomised, Not Treated Due to Site Closure 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.
Overall Study Adverse Event	4	5	0
Overall Study Subject Choice	1	3	0
Overall Study Lost to Follow-up	1	0	0
Overall Study Withdrawal by Subject	4	2	0
Overall Study Others	3	0	0
Overall Study Not treated	3	1	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=97 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=99 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.	Total n=196 Participants Total of all reporting groups
Age, Continuous	73.8 Years STANDARD_DEVIATION 6.60 • n=5 Participants	75.3 Years STANDARD_DEVIATION 6.44 • n=7 Participants	74.5 Years STANDARD_DEVIATION 6.54 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	37 Participants n=7 Participants	73 Participants n=5 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	62 Participants n=7 Participants	123 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	73 Participants n=5 Participants	76 Participants n=7 Participants	149 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	6 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	33 Participants n=5 Participants	34 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	48 Participants n=5 Participants	55 Participants n=7 Participants	103 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=96 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Change From Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Week 12 of Treatment Baseline	13.9 score on a scale Standard Deviation 5.40	13.8 score on a scale Standard Deviation 5.18
Change From Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Week 12 of Treatment Change at Week 12	-0.6 score on a scale Standard Deviation 2.63	-0.4 score on a scale Standard Deviation 3.41

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=86 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=89 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment Marked improvement	0 Participants	0 Participants
Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment Moderate improvement	5 Participants	3 Participants
Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment Minimal improvement	13 Participants	18 Participants
Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment No change	32 Participants	32 Participants
Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment Minimal worsening	30 Participants	28 Participants
Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment Moderate worsening	6 Participants	8 Participants
Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment Marked worsening	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=90 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment Marked improvement	1 Participants	0 Participants
Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment Moderate improvement	3 Participants	10 Participants
Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment Minimal improvement	20 Participants	15 Participants
Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment No change	36 Participants	30 Participants
Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment Minimal worsening	22 Participants	27 Participants
Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment Moderate worsening	1 Participants	8 Participants
Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment Marked worsening	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=96 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Mean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment Baseline	3.4 score on a scale Standard Deviation 2.68	3.1 score on a scale Standard Deviation 2.48
Mean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment Change at Week 12	0.1 score on a scale Standard Deviation 3.20	0.3 score on a scale Standard Deviation 3.25

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=96 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Total Score Week 12 of Treatment Baseline	21.0 score on a scale Standard Deviation 3.63	21.1 score on a scale Standard Deviation 3.22
Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Total Score Week 12 of Treatment Change at Week 12	-1.1 score on a scale Standard Deviation 3.63	-1.7 score on a scale Standard Deviation 3.58

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=96 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment Baseline	17.6 score on a scale Standard Deviation 14.32	19.1 score on a scale Standard Deviation 16.07
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment Change at Week 12	-0.2 score on a scale Standard Deviation 11.07	-2.0 score on a scale Standard Deviation 15.36

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=96 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Change From Baseline in NPI-4 Subscore at Week 12 Baseline	8.2 score on a scale Standard Deviation 6.40	8.6 score on a scale Standard Deviation 7.18
Change From Baseline in NPI-4 Subscore at Week 12 Change at Week 12	-0.4 score on a scale Standard Deviation 5.15	-0.6 score on a scale Standard Deviation 6.79

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=96 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Change From Baseline in NPI-10 Subscore at Week 12 Baseline	13.5 score on a scale Standard Deviation 11.22	14.9 score on a scale Standard Deviation 13.54
Change From Baseline in NPI-10 Subscore at Week 12 Change at Week 12	0.6 score on a scale Standard Deviation 9.32	-1.4 score on a scale Standard Deviation 12.53

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=96 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Change From Baseline in NPI-D (Caregiver Distress) Total Score at Week 12 Baseline	8.8 score on a scale Standard Deviation 7.65	9.4 score on a scale Standard Deviation 8.44
Change From Baseline in NPI-D (Caregiver Distress) Total Score at Week 12 Change at Week 12	-0.2 score on a scale Standard Deviation 6.18	-0.6 score on a scale Standard Deviation 7.28

SECONDARY outcome

Timeframe: From first dose of study drug up to Week 16

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=99 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation TEAEs	67 Participants	70 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation Severe TEAEs	6 Participants	2 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation Serious TEAEs	9 Participants	7 Participants
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	7 Participants	6 Participants

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 6, Week 9 and Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=99 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Number of Participants With Orthostatic Hypotension Week 2	10 Participants	2 Participants
Number of Participants With Orthostatic Hypotension Week 4	9 Participants	7 Participants
Number of Participants With Orthostatic Hypotension Week 6	6 Participants	11 Participants
Number of Participants With Orthostatic Hypotension Week 9	13 Participants	9 Participants
Number of Participants With Orthostatic Hypotension Week 12	7 Participants	9 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to Week 16

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=99 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Number of Participants With Orthostatic Tachycardia	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to Week 16

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=97 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Number of Participants With Markedly Abnormal Laboratory Values Albumin: Markedly Abnormal Low	1 Participants	0 Participants
Number of Participants With Markedly Abnormal Laboratory Values Bilirubin: Markedly Abnormal High	1 Participants	0 Participants
Number of Participants With Markedly Abnormal Laboratory Values Calcium: Markedly Abnormal Low	1 Participants	0 Participants
Number of Participants With Markedly Abnormal Laboratory Values Creatinine: Markedly Abnormal High	0 Participants	2 Participants
Number of Participants With Markedly Abnormal Laboratory Values Gamma Glutamyl Transferase: Markedly Abnormal High	2 Participants	0 Participants
Number of Participants With Markedly Abnormal Laboratory Values Hemoglobin: Markedly Abnormal Low	0 Participants	1 Participants
Number of Participants With Markedly Abnormal Laboratory Values Leukocytes: Markedly Abnormal Low	0 Participants	1 Participants
Number of Participants With Markedly Abnormal Laboratory Values Lymphocytes: Markedly Abnormal Low	4 Participants	1 Participants
Number of Participants With Markedly Abnormal Laboratory Values Neutrophils: Markedly Abnormal Low	1 Participants	1 Participants
Number of Participants With Markedly Abnormal Laboratory Values Phosphate: Markedly Abnormal Low	0 Participants	1 Participants
Number of Participants With Markedly Abnormal Laboratory Values Potassium: Markedly Abnormal Low	1 Participants	0 Participants
Number of Participants With Markedly Abnormal Laboratory Values Potassium: Markedly Abnormal High	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to Week 16

Outcome measures

Outcome measures
Measure	Placebo n=96 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=98 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings QTcF prolongation by >60 milliseconds (ms) from baseline and absolute QTcF >450 ms	2 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings QTcF prolongation to >500 ms	2 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Change from baseline of PR >= 25 percent (%) to an absolute PR value of >220 msec	1 Participants	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Change from baseline of QRS >= 25% to an absolute QRS value of >120 msec	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=98 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) Completed Suicide	0 Participants	0 Participants
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) Suicide Attempt	0 Participants	0 Participants
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	2 Participants
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) Wish to Die	6 Participants	8 Participants
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) Actual Suicidal Thoughts; Non-specific	1 Participants	1 Participants
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	1 Participants
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	0 Participants
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	0 Participants
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	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=99 Participants Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) Baseline	31.3 score on a scale Standard Deviation 18.51	34.5 score on a scale Standard Deviation 18.12
Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III) Change at Week 16	-1.2 score on a scale Standard Deviation 10.97	1.0 score on a scale Standard Deviation 9.22

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 65 other events

Deaths: 1 deaths

Irsenontrine 50 mg

Serious events: 7 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Eisai Medical Information

Eisai, Inc.

Phone: +1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=97 participants at risk Participants received Irsenontrine-matched placebo capsule, orally, once daily for 12 weeks.	Irsenontrine 50 mg n=99 participants at risk Participants received Irsenontrine 50 milligram (mg), capsule, once daily for 12 weeks.
Gastrointestinal disorders Constipation	0.00% 0/97 • From first dose of study drug up to follow up (Week 16)	1.0% 1/99 • Number of events 1 • From first dose of study drug up to follow up (Week 16)
Gastrointestinal disorders Ileal perforation	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)
Infections and infestations Influenza	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)
Infections and infestations Peritonitis	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)
Infections and infestations Pneumonia	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)
Injury, poisoning and procedural complications Accidental overdose	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)
Injury, poisoning and procedural complications Femur fracture	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)
Injury, poisoning and procedural complications Ligament sprain	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)
Injury, poisoning and procedural complications Periprosthetic fracture	0.00% 0/97 • From first dose of study drug up to follow up (Week 16)	1.0% 1/99 • Number of events 1 • From first dose of study drug up to follow up (Week 16)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)
Nervous system disorders Cerebrovascular accident	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)
Nervous system disorders Dementia with Lewy bodies	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	2.0% 2/99 • Number of events 2 • From first dose of study drug up to follow up (Week 16)
Psychiatric disorders Aggression	0.00% 0/97 • From first dose of study drug up to follow up (Week 16)	1.0% 1/99 • Number of events 1 • From first dose of study drug up to follow up (Week 16)
Psychiatric disorders Delirium	0.00% 0/97 • From first dose of study drug up to follow up (Week 16)	1.0% 1/99 • Number of events 1 • From first dose of study drug up to follow up (Week 16)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/97 • From first dose of study drug up to follow up (Week 16)	1.0% 1/99 • Number of events 2 • From first dose of study drug up to follow up (Week 16)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/97 • From first dose of study drug up to follow up (Week 16)	1.0% 1/99 • Number of events 1 • From first dose of study drug up to follow up (Week 16)
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/97 • From first dose of study drug up to follow up (Week 16)	1.0% 1/99 • Number of events 1 • From first dose of study drug up to follow up (Week 16)
Vascular disorders Hypotension	0.00% 0/97 • From first dose of study drug up to follow up (Week 16)	1.0% 1/99 • Number of events 1 • From first dose of study drug up to follow up (Week 16)
Vascular disorders Orthostatic hypotension	1.0% 1/97 • Number of events 1 • From first dose of study drug up to follow up (Week 16)	0.00% 0/99 • From first dose of study drug up to follow up (Week 16)