Clinical trial NCT00566501: Open-Label Extension Study of 23 mg Donepezil SR in Participants With Moderate to Severe Alzheimer's Disease
Official title: Open-Label Extension Study of 23 mg Donepezil SR in Patients With Moderate to Severe Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: Moderate-to-severe
Alzheimer's
Disease
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Eisai Limited
First posted: 2007-12-03
Enrollment: 915
Sex: ALL
Minimum age (years): 45
Maximum age (years): 91
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of long-term administration of 23 milligram (mg) donepezil sustained release (SR) in participants with moderate to severe Alzheimer's disease. Participants who complete study E2020-G000-326 (NCT00478205) with no ongoing serious adverse events (SAEs) and no serious adverse drug reactions will be eligible to enter the open-label extension study.


Eligibility criteria: Inclusion Criteria for Participants:

1. Written informed consent from the participant (if possible) or from the participant's legal guardian or other representative at the time of the Baseline visit, prior to beginning any assessments or activities.
2. Completion of study E2020-G000-326 (NCT00478205) without ongoing SAEs or history of serious adverse drug reactions during study E2020-G000-326 (NCT00478205).
3. Participant must enroll in the present study within 3 days of completion of study E2020-G000-326 (NCT00478205).
4. Health: physically healthy and ambulatory or ambulatory-aided (that is, walker or cane); corrected vision and hearing sufficient for compliance with testing procedures.
5. Co-morbid medical conditions must be well-controlled as determined by the investigator.
6. Participants undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) may be included, provided that doses are within the approved dose range as specified in the Physician's Desk Reference or local equivalent
7. Concomitant Medications: Participants undergoing treatment with the following medications may be enrolled in the study provided the following conditions are met: chronic daily benzodiazepine use if doses are stable within an approved dose range; bronchodilator medications for treatment of chronic obstructive pulmonary disease (COPD) as long as drug is administered via metered dose inhaler within approved dose range; memantine if taken at doses of 20 mg/day or less, provided that the dose is stable.
8. The participants must have a relative/caregiver who supervises the regular taking of the drug at the correct dose and is alert for possible side effects, unless the participant's legal guardian takes on this task.

Inclusion Criteria for Caregivers. Written informed consent will be obtained from the designated caregiver for participation in study assessments. The caregiver must be sufficiently familiar with the participant (as determined by the investigator) to provide accurate data. Specifically, the caregiver must have sufficient contact with the participant to provide accurate reports of the participant's functioning, must be able to observe for possible adverse events, and must be able to accompany the participant to all visits. It is preferable that the caregiver be the same as in study E2020-G000-326 (NCT00478205). If no replacement caregiver is available who meets the caregiver inclusion/exclusion criteria, the participant must be discontinued from the study.

Exclusion Criteria for Participants:

1. No caregiver available to meet the inclusion criteria for caregivers.
2. Participants with any active or clinically-significant conditions affecting absorption, distribution, or metabolism of the study medication (example, inflammatory bowel disease, gastric or duodenal ulcers, hepatic disease, or severe lactose intolerance).
3. Known plan for elective surgery during the study period that would require general anesthesia and administration of neuromuscular blocking agents, such as succinylcholine, to induce paralysis/muscle relaxation. Minor surgery, such as colonoscopy or cataract surgery, will be permitted as long as it does not require the use of these paralytic agents.
4. Participants who are unwilling or unable to fulfill the requirements of the study.
5. Use of any prohibited prior or concomitant medications.
6. Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study.
7. Participant taking concomitant antidepressant medication known to have significant anticholinergic effects, such as tricyclic antidepressants prescribed at doses recommended for the treatment of major depression.
8. Participants who cannot swallow or who have difficulty swallowing whole tablets.
9. Participants taking any alternative medication such as vitamins and/or herbal products or alternative medical techniques such as acupuncture or acupressure specifically for the treatment of Alzheimer's disease.

Exclusion Criteria for Caregivers.

1. Caregivers who are unwilling or unable to give informed consent or otherwise to fulfill the requirements of the study.
2. Any condition that would make the caregiver, in the opinion of the investigator, unsuitable for the study.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From the enrollment of the study up to 30 days after last dose of the study drug (up to 2 years 3 months)
Secondary outcomes:
measure: Percentage of Participants With at Least 1 Treatment-Emergent Abnormal Laboratory Values (TEAVs): Hematology
timeFrame: From the first dose of study drug up to 2 years 3 months
measure: Percentage of Participants With at Least 1 TEAVs for Selected Parameters: Clinical Chemistry
timeFrame: From the first dose of study drug up to 2 years 3 months
measure: Change From Baseline in Severe Impairment Battery (SIB) Total Score
timeFrame: At Baseline, Month 3, Month 6, Month 9 and Month 12
measure: Change From Baseline in Mini-Mental State Examination (MMSE) Total Score
timeFrame: At Baseline, Month 3, Month 6, Month 9 and Month 12
measure: Change From Baseline in Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Severe Scale (ADCS-ADL) Total Score
timeFrame: At Baseline, Month 3, Month 6, Month 9 and Month 12
measure: Change From Baseline in Quality of Life-Alzheimer's Disease (Qol-AD) Total Score
timeFrame: At Baseline, Month 6 and Month 12
measure: Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Total Score
timeFrame: At Baseline, Month 6 and Month 12
measure: Change From Baseline in Screen for Caregiver Objective Burden (SCB) Total Score
timeFrame: At Baseline, Month 6 and Month 12
measure: Change From Baseline in Screen for Caregiver Subjective Burden (SCB) Total Score
timeFrame: At Baseline, Month 6 and Month 12
measure: Number of Participants With Treatment Outcome Scale (TOS) Score
timeFrame: At Months 6 and 12
measure: Goal Attainment Scaling (GAtS) Score Total Score
timeFrame: At Months 6 and 12
Other outcomes:
Locations:
city: Santa Ana
country: United States
facility: Apex Research Institute
state: California
Study officials:
affiliation: Eisai Limited
name: Jane Yardley, Ph.D
role: STUDY_DIRECTOR
References: