A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Donepezil Hydrochloride (E2020) in Patients With Dementia Associated With Cerebrovascular Disease
Overview
- Phase
- Phase 4
- Intervention
- Donepezil matching placebo
- Conditions
- Dementia Associated With Cerebrovascular Disease
- Sponsor
- Eisai Co., Ltd.
- Enrollment
- 302
- Primary Endpoint
- Double Blind (DB) Phase: Clinicians Interview-based Impression of Change-plus Caregiver Input (CIBIC-plus) Score (LOCF)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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).
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 ≤
- •Clinical Dementia Rating (CDR) ≥
- •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.
Exclusion Criteria
- Not provided
Arms & Interventions
Double Blind Phase: Placebo
Participants will receive donepezil matching placebo, once daily in the evening during the double blind period.
Intervention: Donepezil matching placebo
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.
Intervention: Donepezil hydrochloride
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.
Intervention: Donepezil hydrochloride
Outcomes
Primary Outcomes
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.
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.
Secondary Outcomes
- 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)
- Double Blind (DB) Phase: Change From Baseline in Mini-mental State Examination (MMSE) Score (LOCF) at Week 24(Baseline and Week 24)