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Trial record 4 of 81 for:    dementia with lewy bodies

Study To Evaluate the Efficacy, Safety and Tolerability of E2027 in Participants With Dementia With Lewy Bodies

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ClinicalTrials.gov Identifier: NCT03467152
Recruitment Status : Recruiting
First Posted : March 15, 2018
Last Update Posted : October 29, 2018
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
This study will be conducted to compare E2027 to placebo on the cognitive endpoint of Montreal Cognitive Assessment (MoCA) and the global clinical endpoint of Clinician's Interview Based Impression of Change Plus (CIBIC-Plus) Caregiver Input in participants with dementia with Lewy bodies after 12 weeks of treatment.

Condition or disease Intervention/treatment Phase
Dementia With Lewy Bodies Drug: E2027 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled, Double-Blind, Parallel-Group, Randomized, Study To Evaluate the Efficacy, Safety and Tolerability of E2027 in Subjects With Dementia With Lewy Bodies
Actual Study Start Date : May 4, 2018
Estimated Primary Completion Date : March 11, 2020
Estimated Study Completion Date : March 11, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: E2027
Participants will be randomized to receive a 50 milligram (mg) once daily oral dose of E2027 for 12 weeks.
Drug: E2027
Oral hypromellose capsules.
Other Name: 7-(2-Methoxy-3,5-dimethylpyridin-4-yl)-1-[(3S)-tetrahydrofuran-3-yl]-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one maleate

Placebo Comparator: Placebo
Participants will be randomized to receive a 50 mg once daily oral dose of E2027-matched placebo for 12 weeks.
Drug: Placebo
Oral hypromellose capsules




Primary Outcome Measures :
  1. Mean Change from Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at 12 Weeks of Treatment [ Time Frame: Baseline; Week 12 ]
    The MoCA scale assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. It is useful to characterize global cognitive impairment in dementia with Lewy bodies. The total possible score is 30 points; a score of 26 or above is considered normal.

  2. Mean Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-Plus) Scale Score at 12 Weeks of Treatment [ Time Frame: Baseline; Week 12 ]
    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 scores are: 1 (marked improvement), 2 (moderate improvement), 3 (minimal improvement), 4 (no change), 5 (minimal worsening), 6 (moderate worsening), and 7 (marked worsening).


Secondary Outcome Measures :
  1. Mean Change from Baseline in the Neuropsychiatric Inventory (NPI) Total Score at 12 Weeks of Treatment [ Time Frame: Baseline; Week 12 ]
    This 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. The scale also assesses the degree of caregiver or informant distress engendered by each of the symptoms. It is rated from 0 to 144, with higher scores indicating a greater neuropsychiatric disturbance. A subscore covering the domains of delusions, hallucinations, apathy, and depression (NPI-4) will also be derived.

  2. Mean Change from Baseline in the NPI Subscore at 12 Weeks of Treatment [ Time Frame: Baseline; 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. The NPI subscore covers the 4 domains of delusions, hallucinations, apathy, and depression.

  3. Mean Change from Baseline in the NPI Caregiver Score at 12 Weeks of Treatment [ Time Frame: Baseline; 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. The scale also assesses the degree of caregiver distress engendered by each of the symptoms. It is rated from 0 to 144, with higher scores indicating a greater neuropsychiatric disturbance.

  4. Mean Change from Baseline in the Mini-Mental State Examination (MMSE) Total Score at 12 Weeks of Treatment [ Time Frame: Baseline; Week 12 ]
    The MMSE is a 30-point scale that measures orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. Scores range from 0 (most impaired) to 30 (no impairment).

  5. Mean Change from Baseline in the Cognitive Fluctuation Inventory (CFI) Score at 12 Weeks of Treatment [ Time Frame: Baseline; Week 12 ]
    The CFI scale assesses cognitive fluctuation with the same format as the NPI. It evaluates fluctuation in various domains including attention, ability to perform daily functions, orientation, verbal communication and behavior. It is scored based on frequency and severity with a score range of 0 to 12. The scale also assesses the degree of caregiver or informant distress engendered by the symptoms.

  6. Mean Clinician's Global Impression of Change - In Dementia With Lewy Bodies (CGIC-DLB) Scale Score at 12 Weeks of Treatment [ Time Frame: Baseline; Week 12 ]
    The CGIC-DLB scale provides an overall clinician-determined summary measure of change from the participant's clinical status at the Baseline Visit 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.

  7. Percentage of Participants with Adverse Events (AEs), including Severe Adverse Events, Serious AEs, AEs Resulting in Study Discontinuation [ Time Frame: Up to 22 Weeks ]
    Adverse Events (AEs) will be graded for severity on a 3-point scale of mild, moderate, and severe. Severe AEs defined as those AEs that are incapacitating, with inability to work or to perform normal daily activity. A Serious AE is any untoward medical occurrence that at any dose: results in death; is life threatening (ie, 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.

  8. Percentage of Participants with Orthostatic Hypotension and Orthostatic Tachycardia [ Time Frame: Up to 22 Weeks ]
  9. Percentage of Participants with Markedly Abnormal Laboratory Values and Shift from Baseline in Laboratory Values [ Time Frame: Up to 22 Weeks ]
  10. Percentage of Participants with Abnormal Electrocardiogram (ECG) Parameters and ECG Findings [ Time Frame: Up to 22 Weeks ]
  11. Percentage of Participants with Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to 22 Weeks ]
    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 will be reported.

  12. Change from Baseline in Total Score of Unified Parkinson's Disease Rating Scale part III: Motor Examination (UPDRS-III) [ Time Frame: Baseline, Week 12, and Week 16 ]
    The UPDRS scale evaluates extrapyramidal features in motor function in Parkinson's disease. It contains 33 items in 18 categories: (1) speech, (2) facial expression, (3) rigidity, (4) finger tapping, (5) hand movements, (6) supinational and pronation movements of hands, (7) toe tapping, (8) leg agility, (9) arising from chair, (10) gait, (11) freezing of gait, (12) postural stability, (13) posture, (14) body bradykinesia, (15) postural tremor of hands, (16) kinetic tremor of hands, (17) rest tremor amplitude and (18) constancy of rest tremor. Each item is scored 0 to 4, giving a total score range 0 to 132.



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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 ≥14 and ≤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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03467152


Contacts
Contact: Eisai Medical Information 1-888-274-2378 esi_medinfo@eisai.com

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Sponsors and Collaborators
Eisai Inc.

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT03467152     History of Changes
Other Study ID Numbers: E2027-G000-201
2017-003728-64 ( EudraCT Number )
First Posted: March 15, 2018    Key Record Dates
Last Update Posted: October 29, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eisai Inc.:
E2027
Montreal Cognitive Assessment
Neuropsychiatric Inventory
Mini-Mental State Examination
Cognitive Fluctuation Inventory

Additional relevant MeSH terms:
Dementia
Lewy Body Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Movement Disorders
Neurodegenerative Diseases