Dementia Associated With Cerebrovascular DiseasePhase 4NCT02660983

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

A Phase 4 study testing Donepezil hydrochloride in people with Dementia Associated With Cerebrovascular Disease, run by Eisai Co., Ltd. at 31 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 years and older
Conditions the study is for: Dementia Associated With Cerebrovascular Disease
What is being tested?: Donepezil hydrochloride
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 302 participants
Where: 31 sitesSouth Korea
Study dates: 5 Aug 2013to 21 Dec 2018
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients who meet all of the following criteria will be eligible for inclusion in the study:
Male or female, age greater than or equal to (>=) 40 years at the time of informed consent.
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.
Radiological evidence of cerebrovascular disease.
Mini-Mental Status Examination (MMSE) score is ≥ 10 and ≤ 24.
Clinical Dementia Rating (CDR) ≥ 1.

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Outpatients who are physically healthy, and ambulatory or ambulatory-aided (i.e., walker, cane or wheelchair).
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.
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.
Comorbid medical conditions are clinically stable prior to Baseline, unless otherwise specified.

Who cannot join

Patients who meet any of the following criteria will be excluded:
Anti-dementia drug therapy (cholinesterase inhibitors or memantine) within 12 weeks prior to Screening.
Clinical and/or radiological evidence for other serious degenerative neurological disorders or neuropsychiatric disorders.
Known human immunodeficiency virus disease, neurosyphilis, or a history of significant head trauma followed by persistent neurological deficits or known structural brain abnormalities.
Hypothyroidism at Screening.
Vitamin B12 or folate deficiency at Screening.

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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.
Supine diastolic blood pressure ≥ 95 mmHg.
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).
A history of life-threatening arrhythmias.
A history of malignant neoplasms treated within 5 years prior to study entry, current evidence of malignant neoplasm, recurrent, or metastatic disease.
A known or suspected history of drug or alcohol dependency or abuse.
Abnormal clinical laboratory values which are judged clinically significant by the investigator.
Patients who cannot swallow or who have difficulty swallowing whole tablets, as tablets should not be broken or crushed.
Known plan for elective surgery that would require general anesthesia and administration of neuromuscular blocking agents.
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.

Trial locations and contacts

31 sites in 1 country.

City, postcode or hospital

31 sites in 1 country

South Korea31 sites

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

Other trials in South Korea

About this study

Official title: 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).

Read the 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.

Conditions: Dementia Associated With Cerebrovascular Disease
Being tested: Donepezil hydrochloride, Donepezil matching placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Donepezil hydrochlorideDrug
Also called E2020, Aricept
Donepezil matching placeboDrug
Donepezil hydrochlorideDrug
Also called E2020, Aricept

Study groups in NCT02660983
Study group	Role	What they receive
Double Blind Phase: Placebo	Placebo comparator	Participants will receive donepezil matching placebo, once daily in the evening during the double blind period. Receives: Drug: Donepezil matching placebo
Double Blind Phase: Donepezil	Experimental	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. Receives: Drug: Donepezil hydrochloride
Open-Label Extension Phase: Donepezil	Experimental	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. Receives: Drug: Donepezil hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

Double Blind (DB) Phase: Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score (LOCF) at 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.
Measured: Baseline and Week 24
Double Blind (DB) Phase: Clinicians Interview-based Impression of Change-plus Caregiver Input (CIBIC-plus) Score (LOCF)
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.
Measured: Week 24

Secondary outcomes (2)

Double Blind (DB) Phase: Change From Baseline in Mini-mental State Examination (MMSE) Score (LOCF) at 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.
Measured: 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
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.
Measured: Baseline and Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Aug 201321 Dec 2018

First posted21 Jan 2016 (estimated)
Study start5 Aug 2013
Primary completion13 Jul 2018
Study completion21 Dec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Dementia Associated With Cerebrovascular DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 302 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02660983
Sponsor's protocol ID: E2020-K082-418
Status last verified: May 2018
First submitted: 18 Jan 2016
Last updated: 10 Jan 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Dementia Associated With Cerebrovascular Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Donepezil Hydrochloride (E2020) in Patients With Dementia Associated With Cerebrovascular Disease
ClinicalTrials.gov ID: NCT02660983
Acronym / sponsor ID: E2020-K082-418
Conditions: Dementia Associated With Cerebrovascular Disease
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 302 participants (actual)
Lead sponsor: Eisai Co., Ltd.Industry (pharma, biotech, devices)
Study start: 5 Aug 2013 (actual)
Primary completion: 13 Jul 2018 (actual)
Study completion: 21 Dec 2018 (actual)
First posted: 21 Jan 2016 (estimated)
Results: Posted 4 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Double Blind Phase: Placebo	Placebo comparator	Drug: Donepezil matching placeboParticipants will receive donepezil matching placebo, once daily in the evening during the double blind period.
Double Blind Phase: Donepezil	Experimental	Drug: Donepezil hydrochlorideParticipants 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.
Open-Label Extension Phase: Donepezil	Experimental	Drug: Donepezil hydrochlorideAll 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.

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Patients who meet all of the following criteria will be eligible for inclusion in the study:
Male or female, age greater than or equal to (>=) 40 years at the time of informed consent.
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.
Radiological evidence of cerebrovascular disease.
Mini-Mental Status Examination (MMSE) score is ≥ 10 and ≤ 24.

Key exclusion criteria (16 listed)

Anti-dementia drug therapy (cholinesterase inhibitors or memantine) within 12 weeks prior to Screening.
Clinical and/or radiological evidence for other serious degenerative neurological disorders or neuropsychiatric disorders.
Known human immunodeficiency virus disease, neurosyphilis, or a history of significant head trauma followed by persistent neurological deficits or known structural brain abnormalities.
Hypothyroidism at Screening.
Vitamin B12 or folate deficiency at Screening.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Donepezil hydrochlorideAlso: E2020, Aricept	Drug	Double Blind Phase: Donepezil
Donepezil matching placebo	Drug	Double Blind Phase: Placebo
Donepezil hydrochlorideAlso: E2020, Aricept	Drug	Open-Label Extension Phase: Donepezil

Primary outcome

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.
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.

2 secondary outcomes

Double Blind (DB) Phase: Change From Baseline in Mini-mental State Examination (MMSE) Score (LOCF) at Week 24
Time frame: 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

Results and safety

Results posted to the registry on 4 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo in DB Phase Then Donepezil in OLE Phase	154	130
Donepezil in DB Phase Then Donepezil in OLE Phase	148	122

Primary outcome: 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. Least squares mean (Standard Error). Unit: score on a scale

Measure	Double Blind (DB) Phase: Placebo n = 144	Double Blind (DB) Phase: Donepezil n = 133
Value	-2.06 (0.42)	-2.64 (0.44)

Double Blind (DB) Phase: Placebo vs Double Blind (DB) Phase: Donepezil: Difference in least square (LS) means: -0.58 (95% CI -1.79 to 0.63), p = 0.3455, ANCOVA

Population analysed: The FAS, LOCF, included all randomized participants who received at least one dose of study drug and had at least one postdose primary efficacy measurement. Overall number of participants analyzed included participants who were evaluable at a particular time point for this outcome measure.

Primary outcome: Double Blind (DB) Phase: Clinicians Interview-based Impression of Change-plus Caregiver Input (CIBIC-plus) Score (LOCF)

Time frame: Week 24. Least squares mean (Standard Error). Unit: score on a scale

Measure	Double Blind (DB) Phase: Placebo n = 146	Double Blind (DB) Phase: Donepezil n = 135
Value	3.85 (0.07)	3.73 (0.07)

Double Blind (DB) Phase: Placebo vs Double Blind (DB) Phase: Donepezil: Difference in LS means: -0.12 (95% CI -0.32 to 0.09), p = 0.2570, ANCOVA

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of study drug to 30 days after the last dose of study drug (up to 52 weeks [DB Phase: From the first dose of study drug till Week 24; OLE Phase: Post Week 24 till Week 52]). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Double Blind (DB) Phase: Placebo	24 of 153 (15.7%)	73 of 153 (47.7%)	1 of 153
Double Blind (DB) Phase: Donepezil	18 of 147 (12.2%)	86 of 147 (58.5%)	1 of 147
Open Label Extension (OLE) Phase: Donepezil	12 of 161 (7.5%)	63 of 161 (39.1%)	2 of 161

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

31 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Donepezil hydrochloride in people with Dementia Associated With Cerebrovascular Disease, run by Eisai Co., Ltd. at 31 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02660983.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2020.