Trial Outcomes & Findings for Effect of Memantine on Functional Communication in Patients With Alzheimer's Disease (NCT NCT00469456)

Last Updated: 2009-12-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

265 participants

Primary outcome timeframe

Baseline to Week 12

Results posted on

2009-12-24

Participant Flow

The recruitment period was from May 24, 2007 to July 29, 2008 at 25 centers in three countries \[14 in Australia, 3 in New Zealand, 8 in South Africa\].

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.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo, oral administration, twice daily for 12 weeks	Memantine Memantine 20mg (10mg twice daily), oral administration for 12 weeks
Overall Study STARTED	129	135
Overall Study COMPLETED	120	131
Overall Study NOT COMPLETED	9	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo, oral administration, twice daily for 12 weeks	Memantine Memantine 20mg (10mg twice daily), oral administration for 12 weeks
Overall Study Adverse Event	4	3
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	4	1

Baseline Characteristics

Effect of Memantine on Functional Communication in Patients With Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=129 Participants Matching placebo, oral administration, twice daily for 12 weeks	Memantine n=135 Participants Memantine 20mg (10mg twice daily), oral administration for 12 weeks	Total n=264 Participants Total of all reporting groups
Sex: Female, Male Female	74 Participants n=5 Participants	80 Participants n=7 Participants	154 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	55 Participants n=7 Participants	110 Participants n=5 Participants
Region of Enrollment Australia	55 participants n=5 Participants	55 participants n=7 Participants	110 participants n=5 Participants
Region of Enrollment South Africa	58 participants n=5 Participants	62 participants n=7 Participants	120 participants n=5 Participants
Region of Enrollment New Zealand	16 participants n=5 Participants	18 participants n=7 Participants	34 participants n=5 Participants
Age, Customized <=64 years	19 participants n=5 Participants	13 participants n=7 Participants	32 participants n=5 Participants
Age, Customized 65-74 years	33 participants n=5 Participants	51 participants n=7 Participants	84 participants n=5 Participants
Age, Customized 75-84 years	59 participants n=5 Participants	56 participants n=7 Participants	115 participants n=5 Participants
Age, Customized >=85 years	18 participants n=5 Participants	15 participants n=7 Participants	33 participants n=5 Participants
Age Continuous	75.1 years STANDARD_DEVIATION 8.68 • n=5 Participants	74.8 years STANDARD_DEVIATION 8.05 • n=7 Participants	74.9 years STANDARD_DEVIATION 8.35 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants Matching placebo, oral administration, twice daily for 12 weeks	Memantine n=133 Participants Memantine 20mg (10mg twice daily), oral administration for 12 weeks
Change From Baseline in Functional Linguistic Communication Inventory (FLCI) at Week 12	-0.6 Units on a scale Standard Error 0.59	0.7 Units on a scale Standard Error 0.57

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants Matching placebo, oral administration, twice daily for 12 weeks	Memantine n=133 Participants Memantine 20mg (10mg twice daily), oral administration for 12 weeks
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	0.5 Units on a scale Standard Error 1.99

Adverse Events

Placebo

Serious events: 13 serious events

Other events: 2 other events

Deaths: 0 deaths

Memantine

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=129 participants at risk Matching placebo, oral administration, twice daily for 12 weeks	Memantine n=135 participants at risk Memantine 20mg (10mg twice daily), oral administration for 12 weeks
Nervous system disorders Dizziness	1.6% 2/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	5.2% 7/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.

Additional Information

Stephen Graham, PhD

Forest Research Institute, a subsidiary of Forest Laboratories Inc.

Phone: 201-427-8156

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor can review results communications prior to public release \& can embargo communications re: results for 90 days from time submitted to sponsor for review. PI shall not disclose sponsor's confidential info. Upon sponsor's request, PI shall delete any proprietary info \& shall not include raw data in pub. On sponsor's request, PI shall delay submission for any pub while sponsor files patent apps. If trial is multi-center, PI agrees that first publication shall be a multi-center pub.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=129 participants at risk Matching placebo, oral administration, twice daily for 12 weeks	Memantine n=135 participants at risk Memantine 20mg (10mg twice daily), oral administration for 12 weeks
Nervous system disorders Syncope	1.6% 2/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Infections and infestations Urinary Tract Infection	1.6% 2/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Gastrointestinal disorders Abdominal Pain	0.00% 0/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.74% 1/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Cardiac disorders Angina Unstable	0.00% 0/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.74% 1/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Cardiac disorders Atrioventricular Block First Degree	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Hepatobiliary disorders Bile Duct Stone	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Nervous system disorders Cerebellar Infarction	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Gastrointestinal disorders Constipation	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Injury, poisoning and procedural complications Fall	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Injury, poisoning and procedural complications Femur Fracture	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Gastrointestinal disorders Gastric Ulcer	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Infections and infestations Gastrointeritis Yersinia	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Gastrointestinal disorders Hiatus Hernia	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Infections and infestations Pneumonia Aspiration	0.00% 0/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.74% 1/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma of Skin	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Infections and infestations Upper Respiratory Tract Infection	0.78% 1/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.00% 0/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Ear and labyrinth disorders Vestibular Disorder	0.00% 0/129 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.	0.74% 1/135 • Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.