A Study of Donepezil Hydrochloride in Patients With Dementia Associated With Cerebrovascular Disease

December 20, 2019 updated by: Eisai Co., Ltd.

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Donepezil Hydrochloride (E2020) in Patients With Dementia Associated With Cerebrovascular Disease

The primary objectives are to confirm that donepezil hydrochloride has superior efficacy compared with placebo in improving cognitive function, as measured by Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog), and to demonstrate that donepezil hydrochloride has superior efficacy compared with placebo in improving global function, as measured by Clinician's Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus), in patients with dementia associated with cerebrovascular disease (VaD).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a multi-center, randomized, double-blind, placebo-controlled, parallel-group study with an open-label extension. The study consists of 3 phases; screening phase (1 to 4 weeks), double-blind phase (24 weeks), and Open-label extension phase (24 weeks). Participants, who have completed the double-blind phase and want to continue the study participation, can be enrolled in the 24-week open-label extension phase.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
302

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
    • Buk-gu
      • Daegu-si, Buk-gu, Korea, Republic of
    • Bundang-gu
      • Seongnam-si, Bundang-gu, Korea, Republic of
    • Dong-gu
      • Gwangju-si, Dong-gu, Korea, Republic of
    • Dongjak-gu
      • Seoul-si, Dongjak-gu, Korea, Republic of
    • Gangdong-gu
      • Seoul-si, Gangdong-gu, Korea, Republic of
    • Gangnam-gu
      • Seoul-si, Gangnam-gu, Korea, Republic of
    • Gangwon-do
      • Chuncheon-si, Gangwon-do, Korea, Republic of
    • Gwangjin-gu
      • Seoul-si, Gwangjin-gu, Korea, Republic of
    • Gyeonggi-do
      • Anyang-si, Gyeonggi-do, Korea, Republic of
      • Bucheon-si, Gyeonggi-do, Korea, Republic of
      • Goyang-si, Gyeonggi-do, Korea, Republic of
      • Seongnam-si, Gyeonggi-do, Korea, Republic of
      • Suwon-si, Gyeonggi-do, Korea, Republic of
      • Wonmi-Gu, Gyeonggi-do, Korea, Republic of
    • Gyeongsangnam-do
      • Changwon-si, Gyeongsangnam-do, Korea, Republic of
      • Yangsan-si, Gyeongsangnam-do, Korea, Republic of
    • Jongro-gu
      • Seoul-si, Jongro-gu, Korea, Republic of
    • Jung-gu
      • Daegu-si, Jung-gu, Korea, Republic of
      • Incheon-si, Jung-gu, Korea, Republic of
    • Jungnang-Gu
      • Seoul-si, Jungnang-Gu, Korea, Republic of
    • Nam-gu
      • Daegu-si, Nam-gu, Korea, Republic of
    • Namdong-gu
      • Incheon-si, Namdong-gu, Korea, Republic of
    • Seo-gu
      • Busan-si, Seo-gu, Korea, Republic of
    • Seocho-gu
      • Seoul-si, Seocho-gu, Korea, Republic of
    • Seodaemun-Gu
      • Seoul-si, Seodaemun-Gu, Korea, Republic of
    • Seongbuk-gu
      • Seoul-si, Seongbuk-gu, Korea, Republic of
    • Seongdong-gu
      • Seoul-si, Seongdong-gu, Korea, Republic of
    • Seoul
      • Jongno-Gu, Seoul, Korea, Republic of
    • Songpa-Gu
      • Seoul-si, Songpa-Gu, Korea, Republic of
    • Yangcheon-gu
      • Seoul-si, Yangcheon-gu, Korea, Republic of
    • Yeongdeungpo-gu
      • Seoul-si, Yeongdeungpo-gu, Korea, Republic of

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients who meet all of the following criteria will be eligible for inclusion in the study:

  1. Male or female, age greater than or equal to (>=) 40 years at the time of informed consent.
  2. Possible or probable dementia associated with cerebrovascular disease as defined by National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria (NINDS-AIREN Criteria) with dementia of greater than 3 months duration.
  3. Radiological evidence of cerebrovascular disease.
  4. Mini-Mental Status Examination (MMSE) score is ≥ 10 and ≤ 24.
  5. Clinical Dementia Rating (CDR) ≥ 1.
  6. Outpatients who are physically healthy, and ambulatory or ambulatory-aided (i.e., walker, cane or wheelchair).
  7. Written informed consent (IC) is obtained from the patient (if possible) and from the patient's legal guardian prior to being exposed to any study-related procedures. The caregiver must separately provide IC for his/her own participation in the study.
  8. Patients having caregivers who submit written consent to cooperate with this study, have regular contact with the patient (i.e., an average of ≥ 4 hours/day and ≥ 3 days/week), provide patients' information necessary for this study, ensure the regular administration of assigned donepezil, as well as all concomitant therapies, at the correct dose, and escort the patients on required visits to study institution.
  9. Comorbid medical conditions are clinically stable prior to Baseline, unless otherwise specified.

Exclusion Criteria

Patients who meet any of the following criteria will be excluded:

  1. Anti-dementia drug therapy (cholinesterase inhibitors or memantine) within 12 weeks prior to Screening.
  2. Clinical and/or radiological evidence for other serious degenerative neurological disorders or neuropsychiatric disorders.
  3. Known human immunodeficiency virus disease, neurosyphilis, or a history of significant head trauma followed by persistent neurological deficits or known structural brain abnormalities.
  4. Hypothyroidism at Screening.
  5. Vitamin B12 or folate deficiency at Screening.
  6. Evidence of a new transient ischemic attack (TIA) or stroke that occurs within 12 weeks prior to Screening, even if the symptoms are minor and do not require hospitalization, are excluded.
  7. Supine diastolic blood pressure ≥ 95 mmHg.
  8. Complication of sick sinus syndrome, abnormal auricular and atrioventricular (AV) junction conductions (AV block, ≥ II ventricular block, etc.), or with a prolonged QT/QTc interval (> 450 ms) as demonstrated by a repeated electrocardiogram (ECG).
  9. A history of life-threatening arrhythmias.
  10. A history of malignant neoplasms treated within 5 years prior to study entry, current evidence of malignant neoplasm, recurrent, or metastatic disease.
  11. A known or suspected history of drug or alcohol dependency or abuse.
  12. Abnormal clinical laboratory values which are judged clinically significant by the investigator.
  13. Patients who cannot swallow or who have difficulty swallowing whole tablets, as tablets should not be broken or crushed.
  14. Known plan for elective surgery that would require general anesthesia and administration of neuromuscular blocking agents.
  15. Pregnant women, lactating women, or women of child-bearing potential who don't agree to practice effective contraception throughout the entire study period and for 30 days after donepezil discontinuation, or who don't have a negative serum â-Human chorionic gonadotropin (HCG) test result or a negative urine pregnancy test result.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Double Blind Phase: Placebo
Participants will receive donepezil matching placebo, once daily in the evening during the double blind period.
Drug: Donepezil matching placebo
Experimental: Double Blind Phase: Donepezil
Participants will receive donepezil 5 milligram (mg), once daily in the evening during the titration phase and then the dose will be increased to 10 mg at Week 4 during the double blind period. During the maintenance period, dose reduction to 5 mg/day will be permitted only when 10 mg/day is intolerable due to adverse events.
Drug: Donepezil hydrochloride
Other Names:
  • Aricept
  • E2020
Experimental: Open-Label Extension Phase: Donepezil
All participants who will complete the double-blind phase and want to continue the study participation, can be enrolled in the 24-week open-label extension phase. In this phase, treatment will be initiated at 5 mg/day, and the dose will be maintained until Week 6 (Day 28-42). After assessing clinical response during the period by examination, the dose can be increased to 10 mg/day. Dose reduction (from 10 mg/day to 5 mg/day) will be permitted when the investigator judges it difficult to continue the 10 mg/day administration. It will be possible to increase the dose to 10 mg/day again.
Drug: Donepezil hydrochloride
Other Names:
  • Aricept
  • E2020

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Double Blind (DB) Phase: Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score (LOCF) at Week 24
Time Frame: Baseline and Week 24
The ADAS-Cog was a validated psychometric instrument that evaluates memory (word recall, word recognition), attention, reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). The ADAS-cog scores range from 0 to 70, with negative change from baseline indicating clinical improvement. LOCF=last observation carried forward.
Baseline and Week 24
Double Blind (DB) Phase: Clinicians Interview-based Impression of Change-plus Caregiver Input (CIBIC-plus) Score (LOCF)
Time Frame: Week 24
The CIBIC-plus rates change in global functioning relative to baseline on a scale. The score ranges from 1 (Marked improvement) to 7 (Marked worsening). A score of "4" represents no change from baseline. LOCF=last observation carried forward.
Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Double Blind (DB) Phase: Change From Baseline in Mini-mental State Examination (MMSE) Score (LOCF) at Week 24
Time Frame: Baseline and Week 24
MMSE is a well-known, gold standard test for measuring the cognitive state of dementia participants. It includes items evaluating orientation to time and place, recall of objects, attention, language, and conversational abilities. The total score ranges from 0 (most impaired) to 30 (no impairment). The lower score means severe cognitive deficit. A positive change score indicated improvement from baseline. LOCF=last observation carried forward.
Baseline and Week 24
Double Blind (DB) Phase: Change From Baseline in Executive Function Test (Korean Trail Making Test Elderly [K-TMT-e]) Score (LOCF) at Week 24
Time Frame: Baseline and Week 24
The trail making test (TMT) was an evaluation tool used to assess the cognitive function, especially for executive function. The K-TMT-e has two parts that are referred to as part A (component: serial numbers) and part B (component: serial numbers and days). The K-TMT-e was a timed test and the goal was to complete the tests accurately and as quickly as possible. Higher scores reveal greater impairment. K-TMT-e Score was measured as time taken by participants to complete goal. LOCF=last observation carried forward.
Baseline and Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eisai Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 5, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 13, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 21, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 18, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 18, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 21, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 10, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E2020-K082-418

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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