Alzheimer's Disease
Conditions
Keywords
memantine, Alzheimer's Disease, communication
Brief summary
The objective of this study is to evaluate the effect of memantine versus placebo on functional communication in patients with Alzheimer's Disease
Interventions
DRUGMemantine
Memantine 20mg (10mg twice daily) oral administration for 12 weeks
DRUGplacebo
Placebo oral administration twice daily for 12 weeks
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female outpatients, 50 years or older, native English speakers, meeting National Institute of Neurological and Communicative Disorders and Stroke--Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD with a Mini Mental State Examination (MMSE) score of 10 to 19 at Screening and Baseline
Exclusion criteria
* Current Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV) Axis I disorder other than AD * Previous imaging results not consistent with the diagnosis of AD * Modified Hachinski Ischemia Score greater than 4 * Evidence of other neurologic disorders * Clinically significant systemic disease * A known or suspected history of alcohol or drug abuse in the past 5 years * Taking excluded medication * Previous treatment with commercial memantine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Functional Linguistic Communication Inventory (FLCI) at Week 12 | Baseline to Week 12 | FLCI is a standardized & validated instrument for evaluating functional communication in pts with moderate-to-severe Alzheimer's that can be used to obtain Baseline information & to track patients' capabilities thereafter. The FLCI evaluates 10 areas: greeting and naming, answering questions, writing, sign comprehension, object-to-picture matching, word reading and comprehension, following commands, pantomime, gesture, and conversation. The FLCI total score ranges from 0 to 87, a higher score denotes better functional communication, and takes approximately 30 minutes to complete. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in American Speech-Language-Hearing Association Functional Assessment of Communication Skills for Adults (ASHA FACS) [Total Score of Social Communication and Communication of Basic Needs Subscores] at Week 12 | Baseline to Week 12 | The ASHA FACS assesses & measures functional communication skills of adults with speech, language, & cognitive communication disorders. The measure, which comprises 43 items and takes approximately 20 minutes to complete, assesses functional communication in four areas: social communication; communication of basic needs; reading, writing, and number concepts; and daily planning. Total score of subdomains \[Social Communication and Communication of Basic Needs\] ranges from 0-196. A higher score denotes better communication. |
Countries
Australia, New Zealand, South Africa
Participant flow
Recruitment details
The recruitment period was from May 24, 2007 to July 29, 2008 at 25 centers in three countries \[14 in Australia, 3 in New Zealand, 8 in South Africa\].
Pre-assignment details
Study consisted of up to 2 weeks single-blind placebo treatment followed by 12 weeks double-blind treatment. At end of single-blind placebo treatment, patients (pts) meeting entry criteria were randomized (1:1) to 1 of 2 double-blind treatment groups receiving memantine or placebo. Pts not meeting inclusion/exclusion criteria were not randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo, oral administration, twice daily for 12 weeks | 129 |
| Memantine Memantine 20mg (10mg twice daily), oral administration for 12 weeks | 135 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Total | Memantine | Placebo |
|---|---|---|---|
| Age Continuous | 74.9 years STANDARD_DEVIATION 8.35 | 74.8 years STANDARD_DEVIATION 8.05 | 75.1 years STANDARD_DEVIATION 8.68 |
| Age, Customized <=64 years | 32 participants | 13 participants | 19 participants |
| Age, Customized 65-74 years | 84 participants | 51 participants | 33 participants |
| Age, Customized 75-84 years | 115 participants | 56 participants | 59 participants |
| Age, Customized >=85 years | 33 participants | 15 participants | 18 participants |
| Region of Enrollment Australia | 110 participants | 55 participants | 55 participants |
| Region of Enrollment New Zealand | 34 participants | 18 participants | 16 participants |
| Region of Enrollment South Africa | 120 participants | 62 participants | 58 participants |
| Sex: Female, Male Female | 154 Participants | 80 Participants | 74 Participants |
| Sex: Female, Male Male | 110 Participants | 55 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 129 | 7 / 135 |
| serious Total, serious adverse events | 13 / 129 | 4 / 135 |
Outcome results
Primary
Change From Baseline in Functional Linguistic Communication Inventory (FLCI) at Week 12
FLCI is a standardized & validated instrument for evaluating functional communication in pts with moderate-to-severe Alzheimer's that can be used to obtain Baseline information & to track patients' capabilities thereafter. The FLCI evaluates 10 areas: greeting and naming, answering questions, writing, sign comprehension, object-to-picture matching, word reading and comprehension, following commands, pantomime, gesture, and conversation. The FLCI total score ranges from 0 to 87, a higher score denotes better functional communication, and takes approximately 30 minutes to complete.
Time frame: Baseline to Week 12
Population: Primary efficacy analysis was based on the Intent-to-Treat (ITT) Population. The ITT Population will consist of all patients in the Safety Population who had at least one post-Baseline assessment of the primary efficacy parameter, FLCI. The last-observation-carried-forward approach was used to impute missing post-Baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Functional Linguistic Communication Inventory (FLCI) at Week 12 | -0.6 Units on a scale | Standard Error 0.59 |
| Memantine | Change From Baseline in Functional Linguistic Communication Inventory (FLCI) at Week 12 | 0.7 Units on a scale | Standard Error 0.57 |
Comparison: The primary efficacy parameter was change from Baseline to Week 12 in FLCI total score. Missing FLCI total scores at Week 12 were imputed using the last-observation-carried-forward (LOCF) approach.p-value: 0.0795% CI: [-0.1, 2.8]ANCOVA
Secondary
Change From Baseline in American Speech-Language-Hearing Association Functional Assessment of Communication Skills for Adults (ASHA FACS) [Total Score of Social Communication and Communication of Basic Needs Subscores] at Week 12
The ASHA FACS assesses & measures functional communication skills of adults with speech, language, & cognitive communication disorders. The measure, which comprises 43 items and takes approximately 20 minutes to complete, assesses functional communication in four areas: social communication; communication of basic needs; reading, writing, and number concepts; and daily planning. Total score of subdomains \[Social Communication and Communication of Basic Needs\] ranges from 0-196. A higher score denotes better communication.
Time frame: Baseline to Week 12
Population: The secondary efficacy analysis was based on the ITT Population. The last-observation-carried-forward approach was used to impute missing post-Baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in American Speech-Language-Hearing Association Functional Assessment of Communication Skills for Adults (ASHA FACS) [Total Score of Social Communication and Communication of Basic Needs Subscores] at Week 12 | -5.3 Units on a scale | Standard Error 2.06 |
| Memantine | Change From Baseline in American Speech-Language-Hearing Association Functional Assessment of Communication Skills for Adults (ASHA FACS) [Total Score of Social Communication and Communication of Basic Needs Subscores] at Week 12 | 0.5 Units on a scale | Standard Error 1.99 |
Comparison: The secondary efficacy parameter was change from Baseline at Week 12 in the total score of the Social Communication subscale and Communication of Basic Needs subscale of the ASHA FACS. Missing scores at week 12 were imputed using the last-observation-carried-forward (LOCF) approach.p-value: 0.02295% CI: [0.9, 10.9]ANCOVA