CClinicalTrials.gg
Sign In
CompletedNCT03467152Updated Aug 1, 2022Results posted

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

A Phase 2 interventional study of Irsenontrine and Placebo in Dementia With Lewy Bodies, sponsored by Eisai Inc.. Completed at 74 sites in 7 countries. Open to participants aged 50 Years to 85 Years. Per ClinicalTrials.gov, last updated 2022-08-01.

Sponsored by Eisai Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
326
Allocation
Randomized
Ages
50 Years to 85 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Dementia With Lewy Bodies

Keywords

  • Irsenontrine
  • Montreal Cognitive Assessment
  • Neuropsychiatric Inventory
  • Mini-Mental State Examination
  • Cognitive Fluctuation Inventory
03

Who can participate

Ages eligible
50 Years to 85 Years
Sexes eligible
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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
326 participants (actual)

Study arms

  • Experimental
    Irsenontrine

    Participants will be randomized to receive a 50 milligram (mg) once daily oral dose of Irsenontrine for 12 weeks.

    Drug: Irsenontrine

  • 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

Interventions

  • DrugIrsenontrine

    Oral hypromellose capsules.

    Also known as: E2027

  • DrugPlacebo

    Oral hypromellose capsules.

05

What researchers measure

Primary outcomes

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

    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

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

    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

Secondary outcomes

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

    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

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

    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

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

    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

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

    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

  5. Change From Baseline in NPI-4 Subscore at 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.

    Time frame: Baseline and Week 12

  6. Change From Baseline in NPI-10 Subscore at 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.

    Time frame: Baseline and Week 12

  7. Change From Baseline in NPI-D (Caregiver Distress) Total Score at 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.

    Time frame: Baseline and Week 12

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

    A TEAE was defined as an AE that emerged 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

  9. Number of Participants With Orthostatic Hypotension

    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

  10. Number of Participants With Orthostatic Tachycardia

    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

  11. Number of Participants With Markedly Abnormal Laboratory Values

    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

  12. Number of Participants With Abnormal Electrocardiogram (ECG) Findings

    Time frame: 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)

    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

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

    The UPDRS scale evaluates extrapyramidal features in motor function in Parkinson's disease. It contains 33 items in 18 categories: (1) speech, (2) facial expression, (3) rigidity, (4) finger tapping, (5) hand movements, (6) supinational and pronation movements of hands, (7) toe tapping, (8) leg agility, (9) arising from chair, (10) gait, (11) freezing of gait, (12) postural stability, (13) posture, (14) body bradykinesia, (15) postural tremor of hands, (16) kinetic tremor of hands, (17) rest tremor amplitude and (18) constancy of rest tremor. Each item is scored 0 to 4, giving a total score range 0 to 132. Higher scores indicating more severe symptoms.

    Time frame: Baseline up to Week 16

06

Results

Posted Aug 1, 2022

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.

Participant flow — Overall Study
MilestonePlaceboIrsenontrine 50 mgRandomised, Not Treated Due to Site Closure
Started1001006
Treated97990
Completed84890
Not completed16116
Withdrew: Adverse event450
Withdrew: Subject choice130
Withdrew: Lost to follow-up100
Withdrew: Withdrawal by subject420
Withdrew: Others300
Withdrew: Not treated316

Outcome measures

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

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
Reported as:
Mean · score on a scale
Change From Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Week 12 of Treatment
score on a scalePlaceboIrsenontrine 50 mg
Baseline13.9 ± 5.4013.8 ± 5.18
Change at Week 12-0.6 ± 2.63-0.4 ± 3.41
Statistical analysis
  • Placebo vs Irsenontrine 50 mg · MMRM · p = 0.6909 (Mixed Models for Repeated Measures Analysis (MMRM))
PrimaryNumber of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment

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
Reported as:
Count of participants · Participants
Number of Participants Based on Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale at Week 12 of Treatment
ParticipantsPlaceboIrsenontrine 50 mg
Marked improvement00
Moderate improvement53
Minimal improvement1318
No change3232
Minimal worsening3028
Moderate worsening68
Marked worsening00
Statistical analysis
  • Placebo vs Irsenontrine 50 mg · GLMM · p = 0.8251 (Generalized Linear Mixed Models Analysis (GLMM)) · Odds ratio (or): 1.018 · 95% CI 0.695 to 1.492
SecondaryClinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment

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
Reported as:
Count of participants · Participants
Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale at Week 12 of Treatment
ParticipantsPlaceboIrsenontrine 50 mg
Marked improvement10
Moderate improvement310
Minimal improvement2015
No change3630
Minimal worsening2227
Moderate worsening18
Marked worsening00
Statistical analysis
  • Placebo vs Irsenontrine 50 mg · GLMM · p = 0.3003 (Generalized Linear Mixed Models Analysis (GLMM)) · Odds ratio (or): 0.853 · 95% CI 0.584 to 1.247
SecondaryMean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment

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
Reported as:
Mean · score on a scale
Mean Change From Baseline in the Cognitive Fluctuation Inventory (CFI) Score at Week 12 of Treatment
score on a scalePlaceboIrsenontrine 50 mg
Baseline3.4 ± 2.683.1 ± 2.48
Change at Week 120.1 ± 3.200.3 ± 3.25
Statistical analysis
  • Placebo vs Irsenontrine 50 mg · MMRM · p = 0.9198 (Mixed Models for Repeated Measures Analysis (MMRM))
SecondaryMean Change From Baseline in the Mini-Mental State Examination (MMSE) Total Score Week 12 of Treatment

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
Reported as:
Mean · score on a scale
Mean Change From Baseline in the Mini-Mental State Examination (MMSE) Total Score Week 12 of Treatment
score on a scalePlaceboIrsenontrine 50 mg
Baseline21.0 ± 3.6321.1 ± 3.22
Change at Week 12-1.1 ± 3.63-1.7 ± 3.58
Statistical analysis
  • Placebo vs Irsenontrine 50 mg · ANCOVA · p = 0.2909
SecondaryMean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment

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
Reported as:
Mean · score on a scale
Mean Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Total Score at Week 12 of Treatment
score on a scalePlaceboIrsenontrine 50 mg
Baseline17.6 ± 14.3219.1 ± 16.07
Change at Week 12-0.2 ± 11.07-2.0 ± 15.36
Statistical analysis
  • Placebo vs Irsenontrine 50 mg · MMRM · p = 0.6127 (Mixed Models for Repeated Measures Analysis (MMRM))
SecondaryChange From Baseline in NPI-4 Subscore at 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.

Time frame:
Baseline and Week 12
Reported as:
Mean · score on a scale
Change From Baseline in NPI-4 Subscore at Week 12
score on a scalePlaceboIrsenontrine 50 mg
Baseline8.2 ± 6.408.6 ± 7.18
Change at Week 12-0.4 ± 5.15-0.6 ± 6.79
Statistical analysis
  • Placebo vs Irsenontrine 50 mg · MMRM · p = 0.8780 (Mixed Models for Repeated Measures Analysis (MMRM))
SecondaryChange From Baseline in NPI-10 Subscore at 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.

Time frame:
Baseline and Week 12
Reported as:
Mean · score on a scale
Change From Baseline in NPI-10 Subscore at Week 12
score on a scalePlaceboIrsenontrine 50 mg
Baseline13.5 ± 11.2214.9 ± 13.54
Change at Week 120.6 ± 9.32-1.4 ± 12.53
Statistical analysis
  • Placebo vs Irsenontrine 50 mg · MMRM · p = 0.4090 (Mixed Models for Repeated Measures Analysis (MMRM))
SecondaryChange From Baseline in NPI-D (Caregiver Distress) Total Score at 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.

Time frame:
Baseline and Week 12
Reported as:
Mean · score on a scale
Change From Baseline in NPI-D (Caregiver Distress) Total Score at Week 12
score on a scalePlaceboIrsenontrine 50 mg
Baseline8.8 ± 7.659.4 ± 8.44
Change at Week 12-0.2 ± 6.18-0.6 ± 7.28
Statistical analysis
  • Placebo vs Irsenontrine 50 mg · MMRM · p = 0.8736 (Mixed Models for Repeated Measures Analysis (MMRM))
SecondaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation

A TEAE was defined as an AE that emerged 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
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation
ParticipantsPlaceboIrsenontrine 50 mg
TEAEs6770
Severe TEAEs62
Serious TEAEs97
AE Leading to Discontinuation from Study76
SecondaryNumber of Participants With Orthostatic Hypotension

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
Reported as:
Count of participants · Participants
Number of Participants With Orthostatic Hypotension
ParticipantsPlaceboIrsenontrine 50 mg
Week 2102
Week 497
Week 6611
Week 9139
Week 1279
SecondaryNumber of Participants With Orthostatic Tachycardia

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
Reported as:
Count of participants · Participants
Number of Participants With Orthostatic Tachycardia
ParticipantsPlaceboIrsenontrine 50 mg
Number of Participants With Orthostatic Tachycardia10
SecondaryNumber of Participants With Markedly Abnormal Laboratory Values

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
Reported as:
Count of participants · Participants
Number of Participants With Markedly Abnormal Laboratory Values
ParticipantsPlaceboIrsenontrine 50 mg
Albumin: Markedly Abnormal Low10
Bilirubin: Markedly Abnormal High10
Calcium: Markedly Abnormal Low10
Creatinine: Markedly Abnormal High02
Gamma Glutamyl Transferase: Markedly Abnormal High20
Hemoglobin: Markedly Abnormal Low01
Leukocytes: Markedly Abnormal Low01
Lymphocytes: Markedly Abnormal Low41
Neutrophils: Markedly Abnormal Low11
Phosphate: Markedly Abnormal Low01
Potassium: Markedly Abnormal Low10
Potassium: Markedly Abnormal High20
SecondaryNumber of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame:
From first dose of study drug up to Week 16
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
ParticipantsPlaceboIrsenontrine 50 mg
QTcF prolongation by >60 milliseconds (ms) from baseline and absolute QTcF >450 ms20
QTcF prolongation to >500 ms20
Change from baseline of PR >= 25 percent (%) to an absolute PR value of >220 msec11
Change from baseline of QRS >= 25% to an absolute QRS value of >120 msec10
SecondaryNumber of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)

The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories); is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. C-SSRS assess whether participant experience any of the following: completed suicide; suicide attempt (response of "yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). Here, number of participants with positive response ("yes") to suicidal behavior or/and Ideation, any non-suicidal self-injurious behavior was reported.

Time frame:
From first dose of study drug up to Week 16
Reported as:
Count of participants · Participants
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)
ParticipantsPlaceboIrsenontrine 50 mg
Completed Suicide00
Suicide Attempt00
Preparatory Actions Towards Imminent Suicidal Behavior02
Wish to Die68
Actual Suicidal Thoughts; Non-specific11
Actual Suicidal Thoughts with Method; No Intent01
Active Thoughts with Intent00
Active Thoughts with Plan and Intent00
Self-injurious Behavior; No Intent00
SecondaryChange From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III)

The UPDRS scale evaluates extrapyramidal features in motor function in Parkinson's disease. It contains 33 items in 18 categories: (1) speech, (2) facial expression, (3) rigidity, (4) finger tapping, (5) hand movements, (6) supinational and pronation movements of hands, (7) toe tapping, (8) leg agility, (9) arising from chair, (10) gait, (11) freezing of gait, (12) postural stability, (13) posture, (14) body bradykinesia, (15) postural tremor of hands, (16) kinetic tremor of hands, (17) rest tremor amplitude and (18) constancy of rest tremor. Each item is scored 0 to 4, giving a total score range 0 to 132. Higher scores indicating more severe symptoms.

Time frame:
Baseline up to Week 16
Reported as:
Mean · score on a scale
Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III)
score on a scalePlaceboIrsenontrine 50 mg
Baseline31.3 ± 18.5134.5 ± 18.12
Change at Week 16-1.2 ± 10.971.0 ± 9.22

Adverse events

Collected over From first dose of study drug up to follow up (Week 16). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo1/97 (1%)9/97 (9.3%)65/97 (67%)
Irsenontrine 50 mg0/99 (0%)7/99 (7.1%)68/99 (68.7%)
Most frequent serious events
Showing 10 of 19
Most frequent serious events
EventPlaceboIrsenontrine 50 mg
Dementia with Lewy bodiesNervous system disorders1/972/99
Ileal perforationGastrointestinal disorders1/970/99
InfluenzaInfections and infestations1/970/99
PeritonitisInfections and infestations1/970/99
PneumoniaInfections and infestations1/970/99
Accidental overdoseInjury, poisoning and procedural complications1/970/99
Femur fractureInjury, poisoning and procedural complications1/970/99
Ligament sprainInjury, poisoning and procedural complications1/970/99
Colon cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/970/99
Cerebrovascular accidentNervous system disorders1/970/99
Most frequent other events
Showing 10 of 155
Most frequent other events
EventPlaceboIrsenontrine 50 mg
FallInjury, poisoning and procedural complications15/9710/99
Hallucination, visualPsychiatric disorders9/977/99
Urinary tract infectionInfections and infestations5/974/99
NasopharyngitisInfections and infestations3/975/99
DizzinessNervous system disorders1/975/99
ConstipationGastrointestinal disorders4/971/99
DiarrhoeaGastrointestinal disorders3/974/99
Dementia with Lewy bodiesNervous system disorders0/974/99
NauseaGastrointestinal disorders3/971/99
ContusionInjury, poisoning and procedural complications3/971/99

Baseline characteristics

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.

Age, Continuous
Age, Continuous(Years)PlaceboIrsenontrine 50 mgTotal
Mean73.8 ± 6.6075.3 ± 6.4474.5 ± 6.54
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboIrsenontrine 50 mgTotal
Female363773
Male6162123
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboIrsenontrine 50 mgTotal
Hispanic or Latino111728
Not Hispanic or Latino7376149
Unknown or Not Reported13619
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboIrsenontrine 50 mgTotal
American Indian or Alaska Native000
Asian333467
Native Hawaiian or Other Pacific Islander000
Black or African American112
White4855103
More than one race000
Unknown or Not Reported15924
07

Study locations

74 sites
  • Banner Sun Health Research Institute
    Sun City, Arizona 85351, United States
  • Advanced Research Center Inc
    Anaheim, California 92805, United States
  • Parkinsons and Movement Disorders Institute
    Fountain Valley, California 92708, United States
  • Paradigm Clinical Research Centers, Inc
    San Diego, California 92117, United States
  • Syrentis Clinical Research
    Santa Ana, California 92705, United States
  • New England Institute for Clinical Research
    Stamford, Connecticut 06905, United States
  • Miami Jewish Health-Clinical Research
    Miami, Florida 33137, United States
  • Elias Research Associates (Allied Biomedical Research Institute)
    Miami, Florida 33155, United States
  • Pharmax Research of South Florida; Elias Research Associates
    Miami, Florida 33175, United States
  • Compass Research-Bioclinica
    Orlando, Florida 32806, United States
  • Neurology Associates of Ormond Beach
    Ormond Beach, Florida 32174, United States
  • Advanced Research Consultants, Inc.
    Palm Beach Gardens, Florida 33410, United States
  • Anchor Neuroscience
    Pensacola, Florida 32502, United States
  • Compass Research-Bioclinica
    The Villages, Florida 32162, United States
  • Indiana University, Dept of Neurology
    Indianapolis, Indiana 46202, United States
  • University of Kentucky, Dept of Neurology Sanders Brown Center on Aging
    Lexington, Kentucky 40504, United States
  • University of Michigan
    Ann Arbor, Michigan 48106, United States
  • Neurological Associates of Albany, PC
    Albany, New York 12208, United States
  • Columbia University
    New York, New York 10032, United States
  • PMG Research of Winston-Salem, LLC
    Winston-Salem, North Carolina 27103, United States
  • Cleveland Clinic, Lou Ruvo Center for Brain Health at Lakewood Hospital
    Lakewood, Ohio 44107, United States
  • Summit Research Network (Oregon) Inc.
    Portland, Oregon 97210, United States
  • New Orleans Center for Clinical Research
    Knoxville, Tennessee 37920, United States
  • Kerwin Research Center, LLC
    Dallas, Texas 75231-4350, United States
  • University of Virginia Adult Neurology
    Charlottesville, Virginia 22903, United States
  • CHRU Nancy- CMRR de lorraine Hôpital de Brabois-Service de Gériatrie
    Vandœuvre-lès-Nancy, Meurthe-et-Moselle 54500, France
  • Centre de Recherche Clinique - Viellissement-Cerveau-Fragilite (CRC-VCF), Hopital des Charpennes
    Lyon, Villeurbanne 69100, France
  • Centre Memoire du CHRU de Lille
    Lille, 59037, France
  • Hopital Neurologique de Lyon
    Lyon, 69677, France
  • University Hospital de la Timone
    Marseille, 13385, France
  • Centre d'Investigation Clinique (CIC) Hopitaux universitaires Strasbourg HOPITAL DE HAUTEPIERRE - BATIMENT AX5
    Strasbourg, 67000, France
  • Eisai Trial Site #3
    Berlin, 12203, Germany
  • Eisai Trial Site #1
    Kassel, 34128, Germany
  • Eisai Trial Site #2
    Westerstede, 26655, Germany
  • Universita Chieti, CeSI Met
    Chieti, 66100, Italy
  • Clinica Neurologica Azienda Ospedaliera di Padova
    Padova, 35128, Italy
  • Eisai Trial Site #20
    Chiba-shi, Chiba 263-0043, Japan
  • Eisai Trial Site #17
    Fukuoka-shi, Fukuoka 814-0180, Japan
  • Eisai Trial Site #8
    Fujioka-shi, Gunma 375-0017, Japan
  • Eisai Trial Site #12
    Maebashi-shi, Gunma 371-8511, Japan
  • Eisai Trial Site #14
    Miyoshi-shi, Hiroshima 728-0013, Japan
  • Eisai Trial Site #4
    Otake-shi, Hiroshima 739-0651, Japan
  • Eisai Trial Site #2
    Himeji-shi, Hyogo 670-0981, Japan
  • Eisai Trial Site #23
    Yokohama-shi, Kanagawa 225-0013, Japan
  • Eisai Trial Site #11
    Kumamoto-shi, Kumamoto 860-8556, Japan
  • Eisai Trial Site #5
    Nishisonogigun, Nagasaki 851-2103, Japan
  • Eisai Trial Site #9
    Nagaoka-shi, Niigata 940-2302, Japan
  • Eisai Trial Site #3
    Kurashiki-shi, Okayama 710-0813, Japan
  • Eisai Trial Site #1
    Naniwa-ku, Osaka 556-0017, Japan
  • Eisai Trial Site #16
    Sakai-ku, Sakai-shi, Osaka 590-0018, Japan
  • Eisai Trial Site #24
    Suita-shi, Osaka 565-0871, Japan
  • Eisai Trial Site #13
    Suita-shi, Osaka 565-0874, Japan
  • Eisai Trial Site #6
    Kanzaki-gun, Saga 842-0192, Japan
  • Eisai Trial Site #10
    Bunkyo-ku, Tokyo 113-0034, Japan
  • Eisai Trial Site #22
    Mitaka-shi, Tokyo 181-0013, Japan
  • Eisai Trial Site #18
    Setagaya-Ku, Tokyo 158-0098, Japan
  • Eisai Trial Site #19
    Yanai-shi, Yamaguchi 742-1352, Japan
  • Eisai Trial Site #25
    Hiroshima, 732-0066, Japan
  • Eisai Trial Site #21
    Osaka, 550-0012, Japan
  • Hospital Mutua de Terrassa
    Terrassa, Barcelona 08221, Spain
  • Hospital Universitario Puerta de Hierro - Majadahonda
    Majadahonda, Madrid 28222, Spain
  • Institut Internacional de Neurociències Aplicades
    Barcelona, 08006, Spain
  • Fundacio ACE
    Barcelona, 08228, Spain
  • Hospital Universitari Vall d'Hebron
    Barcelona, 08235, Spain
  • Hospital General Universitario Gregorio Maranon
    Madrid, 28007, Spain
  • Dementia Research Unit
    Crowborough, East Sussex TN6 1HB, United Kingdom
  • Memory Assessment and Research Centre, Moorgreen Hospital
    Southampton, Hampshire S030 3JB, United Kingdom
  • Clinical Research Centre (CRC)
    Dundee, Scotland DD1 9SY, United Kingdom
  • Queen Elizabeth University Hospital
    Glasgow, Scotland G51 4TF, United Kingdom
  • West London Mental Health Trust
    Isleworth, TW7 6FY, United Kingdom
  • Kings College
    London, SE5 8AF, United Kingdom
  • Cognition Health
    London, W1G 9JF, United Kingdom
  • Manchester Mental Health and Social Care Trust
    Manchester, M25 3BL, United Kingdom
  • Newcastle General Hospital
    Newcastle, NE45PL, United Kingdom
08

References and documents

Study documents

  • Study protocol · Jan 3, 2020
  • Statistical analysis plan · Apr 14, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03467152
Lead sponsor
Eisai Inc.
Responsible party
Sponsor
First posted
Mar 15, 2018
Start date
May 4, 2018
Primary completion
Apr 15, 2020
Completion
Apr 15, 2020
Results posted
Aug 1, 2022
Last update
Aug 1, 2022

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Dementia→

Other studies from this sponsor

Eisai Inc.

Start the discussion