Safety and Efficacy of Donepezil HCl 23 mg in Patients With Moderate to Severe Alzheimer's Disease (SAVE)

This is a multi-center, open-label, single-arm, prospective, phase IV trial, evaluating safety and efficacy of donepezil hydrochloride in patients with moderate to severe Alzheimer's disease.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Donepezil HCL

Detailed Description

This study consisted of pre-treatment and treatment phase. Pre-treatment phase was approximately 4 weeks including the screening and baseline process. In treatment phase, about 190 subjects received Donepezil HCl 23 mg once daily for 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
  • Daegu, Korea, Republic of
  • Daejeon, Korea, Republic of
  • Incheon, Korea, Republic of
  • Jeju, Korea, Republic of
  • Seoul, Korea, Republic of
  • Chungcheongbuk-do
    • Chungju, Chungcheongbuk-do, Korea, Republic of
  • Gyeonggi-do
    • Ansan, Gyeonggi-do, Korea, Republic of
    • Buchoen, Gyeonggi-do, Korea, Republic of
    • Seongnam, Gyeonggi-do, Korea, Republic of
  • Gyeongsangnam-do
    • Jinju, Gyeongsangnam-do, Korea, Republic of
  • Jeollabuk-do
    • Iksan, Jeollabuk-do, Korea, Republic of
  • Jeollanam-do
    • Hwasun, Jeollanam-do, Korea, Republic of

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Male or female aged 45 to 90 years
2. Patients have eligible conditions of dementia diagnosis listed in DSM-IV
3. Diagnosed as a probable Alzheimer's Disease patient according to NINCDS-ADRDA criteria
4. At the timing of screening, MMSE less than or equal to 20 AND CDR greater than or equal to 2 OR GDS greater than or equal to 4
5. Patients, who have been taking stable donepezil 10 mg for 3 months or longer before the start of the study (screening visit), are evaluated as eligible to take donepezil 23 mg by investigator
6. Patients who have not received any other medications for AD such as AChE inhibitors at least for 3 months prior to the screening visit excluding donepezil hydrochloride (However, concomitant use of memantine is allowed if taken at stable dose that are less than or equal to the approved dose range for at least 3 months prior to screening)
7. Medicines for cerebral activation such as Gingko Biloba is allowed to be taken if the patient has received it as stable dose for 3 months prior to the screening visit

Exclusion Criteria

1. Patients who have been participated in any other clinical trial 3 months prior to the screening visit
2. Patients who are having any severe psychiatric disorder or schizophrenia
3. Patients who are having a neurological disorder other than AD which affect the subject's cognition or ability to assess the cognition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: donepezil HCl 23 mg; Donepezil HCl 23 mg once daily, just before bed, for 24 weeks	Drug: Donepezil HCL; Donepezil HCl 23 mg once daily, just before bed, for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Summary of Adverse Events (AEs)	Safety of study drug was assessed by clinical laboratory assessments, vital signs, weight, 12-lead electrocardiogram (ECG), physical and neurological examination. Treatment-Emergent Adverse Events (TEAEs) were defined as any event not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Serious adverse events were defined as AEs that led to or were life-threatening, resulted in or prolonged hospitalization, caused important or long-lasting disability, caused congenital abnormality or malformation, or resulted in death. Adverse drug reactions were defined as any harmful or unintended reaction to study treatment and were considered possibly related or probably related to study drug. Specific AEs and SAEs due to changes in clinical laboratory assessments, vital signs, weight, ECG, and physical and neurological exam are listed in the safety section.	Baseline (Day 1) up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Mini-Mental State Examination (MMSE) Score	The MMSE was used to measure cognitive impairment. The MMSE can evaluate overall cognitive function, and is widely used for the assessment of cognitive impairment in dementia patients. The questionnaire consists of 11 items, and each item aims to evaluate different cognitive domains such as orientation, memory, attention, and construction. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from baseline. The mean change was analyzed by Wilcoxon's signed rank test.	Baseline, Week 12, and Week 24 (Final visit)
Change From Baseline in the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Distress Total Scores	The NPI-Q assessed twelve behavioral domains common in dementia including; hallucinations, delusions, agitation/aggression, dysphoria/depression, anxiety, irritability, disinhibition, euphoria, apathy, aberrant motor behavior, sleep/night-time behavior change, and appetite/eating change. The questionnaire is given by the clinician to the patient's caregiver who was asked if the behavior described is present in the patient. If "Yes", the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale (1 = mild, 2= moderate, and 3= severe) and the associated impact of the symptom manifestations on them (i.e. Caregiver Distress) using a 5-point scale (0 = not distressing at all, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = extreme or very severe). The total severity score represents the sum of individual scores and ranges from 0 to 36. The total distress score represents the sum of individual symptom scores and ranges from 0 to 60.	Baseline, Week 12, and Week 24 (Follow up visit)

Collaborators and Investigators

• Sponsor: Eisai Korea Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 25, 2014
• First Posted (ESTIMATE): March 26, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): June 27, 2016
• Last Update Submitted That Met QC Criteria: May 20, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Alzheimer's disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: ART-M082-401