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

NCT02660983 | Completed Phase 4 Results

• 1 other identifier: E2020-K082-418
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 31

Brief Summary

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).

Conditions

Dementia Associated With Cerebrovascular Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Week 24

Secondary Outcomes (2)

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

  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

  Baseline and Week 24

Study Arms (3)

Double Blind Phase: Placebo

PLACEBO COMPARATOR

Participants will receive donepezil matching placebo, once daily in the evening during the double blind period.

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.

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.

Drug: Donepezil hydrochloride

Interventions

Donepezil hydrochloride DRUG

Also known as: E2020, Aricept

Double Blind Phase: Donepezil

Donepezil matching placebo DRUG

Double Blind Phase: Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (31)

Unknown Facility

Daegu, Buk-gu, South Korea

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Seongnam-si, Bundang-gu, South Korea

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Gwangju, Dong-gu, South Korea

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Seoul, Dongjak-gu, South Korea

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Seoul, Gangdong-gu, South Korea

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Seoul, Gangnam-gu, South Korea

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Chuncheon, Gangwon-do, South Korea

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Seoul, Gwangjin-gu, South Korea

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Anyang-si, Gyeonggi-do, South Korea

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Bucheon-si, Gyeonggi-do, South Korea

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Goyang-si, Gyeonggi-do, South Korea

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Seongnam-si, Gyeonggi-do, South Korea

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Suwon, Gyeonggi-do, South Korea

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Wonmi-gu, Gyeonggi-do, South Korea

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Changwon-si, Gyeongsangnam-do, South Korea

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Yangsan, Gyeongsangnam-do, South Korea

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Seoul, Jongro-gu, South Korea

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Daegu, Jung-gu, South Korea

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Incheon, Jung-gu, South Korea

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Seoul, Jungnang-Gu, South Korea

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Daegu, Nam-gu, South Korea

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Incheon, Namdong-gu, South Korea

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Busan, Seo-gu, South Korea

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Seoul, Seocho-gu, South Korea

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Seoul, Seodaemun-Gu, South Korea

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Seoul, Seongbuk-gu, South Korea

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Seoul, Seongdong-gu, South Korea

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Jongno-Gu, Seoul, South Korea

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Seoul, Songpa-Gu, South Korea

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Seoul, Yangcheon-gu, South Korea

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Unknown Facility

Seoul, Yeongdeungpo-gu, South Korea

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MeSH Terms

Interventions

Donepezil

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Inquiry Service
• Organization: Eisai Co., Ltd.

eisai-chiken_hotline@hhc.eisai.co.jp

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2016
• First Posted: January 21, 2016
• Study Start: August 5, 2013
• Primary Completion: July 13, 2018
• Study Completion: December 21, 2018
• Last Updated: January 10, 2020
• Results First Posted: October 4, 2019

Record last verified: 2018-05

Locations

KR (31)