CompletedPhase 2Results posted

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

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

Lead sponsor

Eisai Inc.

Asset

Irsenontrine

Listed sites

Recruiting sites

Enrollment

326

actual

Study population

Lewy body dementia

Key I/E criteria

•Dementia with Lewy bodies•Study partner/caregiver required•Background AD symptomatic therapy, if used: stable ≥12 weeks

Primary endpoints

•Montreal Cognitive Assessment (MoCA)•Number of Participants

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2017-003728-64

Org study IDE2027-G000-201

NCT IDNCT03467152

Timeline

Milestones

Study first posted2018-03-15actual

Study start2018-05-04actual

Primary completion2020-04-15actual

Study completion2020-04-15actual

Last update posted2022-08-01actual

Results first posted2022-08-01actual

Assets

Drug assets

Irsenontrine

Study populations

Who this study enrolls

Lewy body dementia

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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.

Endpoints (32)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Behavior / neuropsychiatric

Global cognition

Executive function / language

Safety / tolerability / PK

Other (unclassified)

Function / daily living

Other clinical outcomes

Global cognition

6 endpoints

Primary/protocol endpoint

Change From Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Week 12 of Treatment

Time frame:Baseline and Week 12

Montreal Cognitive Assessment (MoCA)

change from baseline, improvement

Primary/registry result

Change From Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Week 12 of Treatment

Time frame:Baseline and Week 12

Montreal Cognitive Assessment (MoCA)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboBaselinen=92 Participants	13.9	5.40
Change at Week 12n=81 Participants	-0.6	2.63
Irsenontrine 50 mgBaselinen=96 Participants	13.8	5.18
Change at Week 12n=87 Participants	-0.4	3.41

p0.6909MMRM

Secondary/protocol endpoint

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

Time frame:Week 12

event count, event

Secondary/protocol endpoint

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

Time frame:Baseline and Week 12

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

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

Time frame:Week 12

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboMarked improvementn=83 Participants	1	-
Moderate improvementn=83 Participants	3	-
Minimal improvementn=83 Participants	20	-
No changen=83 Participants	36	-
Minimal worseningn=83 Participants	22	-
Moderate worseningn=83 Participants	1	-
Marked worseningn=83 Participants	0	-
Irsenontrine 50 mgMarked improvementn=90 Participants	0	-
Moderate improvementn=90 Participants	10	-
Minimal improvementn=90 Participants	15	-
No changen=90 Participants	30	-
Minimal worseningn=90 Participants	27	-
Moderate worseningn=90 Participants	8	-
Marked worseningn=90 Participants	0	-

Odds Ratio (OR)0.85395% CI0.584 - 1.247p0.3003GLMM

Secondary/registry result

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

Time frame:Baseline and Week 12

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboBaselinen=93 Participants	21.0	3.63
Change at Week 12n=85 Participants	-1.1	3.63
Irsenontrine 50 mgBaselinen=96 Participants	21.1	3.22
Change at Week 12n=92 Participants	-1.7	3.58

p0.2909ANCOVA

Executive function / language

4 endpoints

Secondary/protocol endpoint

Mean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment

Time frame:Baseline and Week 12

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Baseline up to Week 16

change from baseline, improvement

Secondary/registry result

Mean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment

Time frame:Baseline and Week 12

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboBaselinen=92 Participants	3.4	2.68
Change at Week 12n=86 Participants	0.1	3.20
Irsenontrine 50 mgBaselinen=96 Participants	3.1	2.48
Change at Week 12n=89 Participants	0.3	3.25

p0.9198MMRM

Secondary/registry result

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

Time frame:Baseline up to Week 16

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboBaselinen=97 Participants	31.3	18.51
Change at Week 16n=81 Participants	-1.2	10.97
Irsenontrine 50 mgBaselinen=99 Participants	34.5	18.12
Change at Week 16n=84 Participants	1.0	9.22

Function / daily living

2 endpoints

Primary/protocol endpoint

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

Time frame:Week 12

event count, event

Primary/registry result

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

Time frame:Week 12

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboMarked improvementn=86 Participants	0	-
Moderate improvementn=86 Participants	5	-
Minimal improvementn=86 Participants	13	-
No changen=86 Participants	32	-
Minimal worseningn=86 Participants	30	-
Moderate worseningn=86 Participants	6	-
Marked worseningn=86 Participants	0	-
Irsenontrine 50 mgMarked improvementn=89 Participants	0	-
Moderate improvementn=89 Participants	3	-
Minimal improvementn=89 Participants	18	-
No changen=89 Participants	32	-
Minimal worseningn=89 Participants	28	-
Moderate worseningn=89 Participants	8	-
Marked worseningn=89 Participants	0	-

Odds Ratio (OR)1.01895% CI0.695 - 1.492p0.8251GLMM

Behavior / neuropsychiatric

10 endpoints

Secondary/protocol endpoint

Mean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment

Time frame:Baseline and Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in NPI-4 Subscore at Week 12

Time frame:Baseline and Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in NPI-10 Subscore at Week 12

Time frame:Baseline and Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in NPI-D (Caregiver Distress) Total Score at Week 12

Time frame:Baseline and Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:From first dose of study drug up to Week 16

event count, event

Secondary/registry result

Mean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment

Time frame:Baseline and Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboBaselinen=93 Participants	17.6	14.32
Change at Week 12n=86 Participants	-0.2	11.07
Irsenontrine 50 mgBaselinen=96 Participants	19.1	16.07
Change at Week 12n=89 Participants	-2.0	15.36

p0.6127MMRM

Secondary/registry result

Change From Baseline in NPI-4 Subscore at Week 12

Time frame:Baseline and Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboBaselinen=93 Participants	8.2	6.40
Change at Week 12n=86 Participants	-0.4	5.15
Irsenontrine 50 mgBaselinen=96 Participants	8.6	7.18
Change at Week 12n=89 Participants	-0.6	6.79

p0.8780MMRM

Secondary/registry result

Change From Baseline in NPI-10 Subscore at Week 12

Time frame:Baseline and Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboBaselinen=93 Participants	13.5	11.22
Change at Week 12n=86 Participants	0.6	9.32
Irsenontrine 50 mgBaselinen=96 Participants	14.9	13.54
Change at Week 12n=89 Participants	-1.4	12.53

p0.4090MMRM

Secondary/registry result

Change From Baseline in NPI-D (Caregiver Distress) Total Score at Week 12

Time frame:Baseline and Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
PlaceboBaselinen=93 Participants	8.8	7.65
Change at Week 12n=86 Participants	-0.2	6.18
Irsenontrine 50 mgBaselinen=96 Participants	9.4	8.44
Change at Week 12n=89 Participants	-0.6	7.28

p0.8736MMRM

Secondary/registry result

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

Time frame:From first dose of study drug up to Week 16

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboCompleted Suiciden=95 Participants	0	-
Suicide Attemptn=95 Participants	0	-
Preparatory Actions Towards Imminent Suicidal Behaviorn=95 Participants	0	-
Wish to Dien=95 Participants	6	-
Actual Suicidal Thoughts; Non-specificn=95 Participants	1	-
Actual Suicidal Thoughts with Method; No Intentn=95 Participants	0	-
Active Thoughts with Intentn=95 Participants	0	-
Active Thoughts with Plan and Intentn=95 Participants	0	-
Self-injurious Behavior; No Intentn=95 Participants	0	-
Irsenontrine 50 mgCompleted Suiciden=98 Participants	0	-
Suicide Attemptn=98 Participants	0	-
Preparatory Actions Towards Imminent Suicidal Behaviorn=98 Participants	2	-
Wish to Dien=98 Participants	8	-
Actual Suicidal Thoughts; Non-specificn=98 Participants	1	-
Actual Suicidal Thoughts with Method; No Intentn=98 Participants	1	-
Active Thoughts with Intentn=98 Participants	0	-
Active Thoughts with Plan and Intentn=98 Participants	0	-
Self-injurious Behavior; No Intentn=98 Participants	0	-

Safety / tolerability / PK

4 endpoints

Secondary/protocol endpoint

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation

Time frame:From first dose of study drug up to Week 16

event count, event

Secondary/protocol endpoint

Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Time frame:From first dose of study drug up to Week 16

event count, event

Secondary/registry result

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation

Time frame:From first dose of study drug up to Week 16

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboTEAEsn=97 Participants	67	-
Severe TEAEsn=97 Participants	6	-
Serious TEAEsn=97 Participants	9	-
AE Leading to Discontinuation from Studyn=97 Participants	7	-
Irsenontrine 50 mgTEAEsn=99 Participants	70	-
Severe TEAEsn=99 Participants	2	-
Serious TEAEsn=99 Participants	7	-
AE Leading to Discontinuation from Studyn=99 Participants	6	-

Secondary/registry result

Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Time frame:From first dose of study drug up to Week 16

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboQTcF prolongation by >60 milliseconds (ms) from baseline and absolute QTcF >450 msn=96 Participants	2	-
QTcF prolongation to >500 msn=96 Participants	2	-
Change from baseline of PR >= 25 percent (%) to an absolute PR value of >220 msecn=96 Participants	1	-
Change from baseline of QRS >= 25% to an absolute QRS value of >120 msecn=96 Participants	1	-
Irsenontrine 50 mgQTcF prolongation by >60 milliseconds (ms) from baseline and absolute QTcF >450 msn=98 Participants	0	-
QTcF prolongation to >500 msn=98 Participants	0	-
Change from baseline of PR >= 25 percent (%) to an absolute PR value of >220 msecn=98 Participants	1	-
Change from baseline of QRS >= 25% to an absolute QRS value of >120 msecn=98 Participants	0	-

Other clinical outcomes

2 endpoints

Secondary/protocol endpoint

Number of Participants With Orthostatic Hypotension

Time frame:Week 2, Week 4, Week 6, Week 9 and Week 12

event count, event

Secondary/registry result

Number of Participants With Orthostatic Hypotension

Time frame:Week 2, Week 4, Week 6, Week 9 and Week 12

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboWeek 2n=97 Participants	10	-
Week 4n=97 Participants	9	-
Week 6n=97 Participants	6	-
Week 9n=97 Participants	13	-
Week 12n=97 Participants	7	-
Irsenontrine 50 mgWeek 2n=99 Participants	2	-
Week 4n=99 Participants	7	-
Week 6n=99 Participants	11	-
Week 9n=99 Participants	9	-
Week 12n=99 Participants	9	-

Other (unclassified)

4 endpoints

Secondary/protocol endpoint/low confidence

Number of Participants With Orthostatic Tachycardia

Time frame:From first dose of study drug up to Week 16

event count, event

Secondary/protocol endpoint/low confidence

Number of Participants With Markedly Abnormal Laboratory Values

Time frame:From first dose of study drug up to Week 16

event count, event

Secondary/registry result/low confidence

Number of Participants With Orthostatic Tachycardia

Time frame:From first dose of study drug up to Week 16

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Placebon=97 Participants	1	-
Irsenontrine 50 mgn=99 Participants	0	-

Secondary/registry result/low confidence

Number of Participants With Markedly Abnormal Laboratory Values

Time frame:From first dose of study drug up to Week 16

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboAlbumin: Markedly Abnormal Lown=94 Participants	1	-
Bilirubin: Markedly Abnormal Highn=94 Participants	1	-
Calcium: Markedly Abnormal Lown=94 Participants	1	-
Creatinine: Markedly Abnormal Highn=94 Participants	0	-
Gamma Glutamyl Transferase: Markedly Abnormal Highn=94 Participants	2	-
Hemoglobin: Markedly Abnormal Lown=94 Participants	0	-
Leukocytes: Markedly Abnormal Lown=94 Participants	0	-
Lymphocytes: Markedly Abnormal Lown=94 Participants	4	-
Neutrophils: Markedly Abnormal Lown=94 Participants	1	-
Phosphate: Markedly Abnormal Lown=94 Participants	0	-
Potassium: Markedly Abnormal Lown=94 Participants	1	-
Potassium: Markedly Abnormal Highn=94 Participants	2	-
Irsenontrine 50 mgAlbumin: Markedly Abnormal Lown=96 Participants	0	-
Bilirubin: Markedly Abnormal Highn=96 Participants	0	-
Calcium: Markedly Abnormal Lown=96 Participants	0	-
Creatinine: Markedly Abnormal Highn=96 Participants	2	-
Gamma Glutamyl Transferase: Markedly Abnormal Highn=96 Participants	0	-
Hemoglobin: Markedly Abnormal Lown=96 Participants	1	-
Leukocytes: Markedly Abnormal Lown=96 Participants	1	-
Lymphocytes: Markedly Abnormal Lown=96 Participants	1	-
Neutrophils: Markedly Abnormal Lown=96 Participants	1	-
Phosphate: Markedly Abnormal Lown=96 Participants	1	-
Potassium: Markedly Abnormal Lown=97 Participants	0	-
Potassium: Markedly Abnormal Highn=97 Participants	0	-

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Oosthoek M, In 't Veld SGJG, Vermunt L, Ye Y, van Ingen M, Koel-Simmelink M, Vijverberg EGB, Saxena S, Hersch S, Irizarry M, Sachdev P, Teunissen CE. Effects of the novel phosphodiesterase 9 inhibitor irsenontrine on CSF proteomics profile in Abeta+ and Abeta- dementia with Lewy bodies patients. Alzheimers Res Ther. 2026 Apr 24;18(1):139. doi: 10.1186/s13195-026-02065-w.
PMID42026627via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.