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The primary objective of this study is to examine the efficacy of memantine on cognition and behavioural symptoms in outpatients with moderate to severe dementia of the Alzheimer's type.
Memantine is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Results from clinical trials in patients with moderate to severe Alzheimer's Disease (AD) have demonstrated memantine's efficacy and safety by showing positive treatment effects on cognitive, global and functional decline.
This 24-week randomised, double-blind, placebo-controlled, multicentre study examines the effect of memantine 20 mg, administered once daily, on cognitive and behavioural symptoms in outpatients diagnosed with moderate to severe AD and significant psychopathology.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Memantine | Experimental |
| |
| Placebo | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Memantine | Drug | 20 mg Oral Tablets Once Daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Memantine on Behavioural Symptoms in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the NPI - 12 Items Version Total Score. | Change from Baseline in Neuropsychiatric Inventory (NPI) total score. NPI is a validated scale that assesses behavioural disturbances in patients with dementia. The 12 item version consists of 10 behavioural and 2 neurovegetative areas. It provides both a total score as well as scores for a number of sub-scales. The frequency, severity and caregiver distress for each domain are measured. The NPI is based upon responses obtained from the caregiver. The total score is from 0 to 144. A higher score reflects more frequency and severity of the disturbances. | Baseline to Week 24 |
| Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score. | Change from Baseline in Severe Impairment Battery (SIB) total score. SIB is a validated scale used to assess cognitive function in patients with moderate to severe dementia. Items are single words or one-step commands combined with gestures. Nine domains are assessed, and the total score is between 0 and 100. A lower total score reflects the loss of cognitive function. | Baseline to Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Memantine on Global Condition Using CIBIC-plus. | Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus). Improvement evaluated with reference to Baseline. CIBIC-plus is a global rating that is derived through an independent, comprehensive interview with the patient and caregiver by a rater who is barred from knowledge of all other psychometric test scores conducted as part of this protocol as well as from reported safety data. The rating is made on a 7-point scale ranging from "1 = marked improvement" to "7 = marked worsening". A score of "4" indicates no change. |
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Inclusion Criteria:
Outpatients who:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Email contact via H. Lundbeck A/S | LundbeckClinicalTrials@lundbeck.com | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CA019 | Edmonton | Alberta | T5G 0B7 | Canada | ||
| CA033 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23472619 | Result | Herrmann N, Gauthier S, Boneva N, Lemming OM; 10158 Investigators. A randomized, double-blind, placebo-controlled trial of memantine in a behaviorally enriched sample of patients with moderate-to-severe Alzheimer's disease. Int Psychogeriatr. 2013 Jun;25(6):919-27. doi: 10.1017/S1041610213000239. Epub 2013 Mar 8. |
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At the Baseline Visit, the patients were randomised (1:1) to 24 weeks of treatment with placebo or memantine. Patients randomised to memantine were up-titrated in weekly increments of 5 mg over a 4-week dose-escalation period. The target dose of 20 mg/day was administered at the start of the fourth week and maintained for the rest of the study.
The patients were recruited from the investigators' outpatient clinics.
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| ID | Title | Description |
|---|---|---|
| FG000 | Memantine | 20 mg Oral Tablets Once Daily |
| FG001 | Placebo | Oral Tablets Once Daily |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo | Drug | Oral Tablets Once Daily |
|
| Baseline to Week 24 |
| Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score. | Change from Baseline on the Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) 19-item version total score. ADCS-ADL- 19 items version for moderate to severe AD will measure patient's functioning. This battery of ADL questions is used here to measure the functional capabilities of patients with dementia. The inventory is done by interviewing a person in close contact with the patient and covers the most usual and consistent performance of the patient over the preceding 4 weeks. Total score is from 0 to 54. The higher score, the lower impairment. | Baseline to Week 24 |
| Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score. | Change from Baseline on the Cohen-Mansfield Agitation Inventory (CMAI) - Long Form total score. CMAI - Long Form looks specifically at agitated behaviour in patients with cognitive impairment. It is a seven-point rating scale assessing the frequency of up to 29 agitated behaviours, ranging from "1 = Never" to "7 = Several times an hour". Rating is based on responses obtained from interviews with the caregiver. The total score ranges from 29 to 203, with a higher score reflecting more frequent behavioural disturbances. | Baseline to Week 24 |
| Kelowna |
| British Columbia |
| V1W 4V5 |
| Canada |
| CA034 | Winnipeg | Manitoba | R3M 0X9 | Canada |
| CA022 | Saint John | New Brunswick | Canada |
| CA046 | Kentville | Nova Scotia | B4N 4K9 | Canada |
| CA045 | Pictou | Nova Scotia | B0K 1H0 | Canada |
| CA032 | Burlington | Ontario | L7M 4Y1 | Canada |
| CA029 | Orangeville | Ontario | L9W 2E1 | Canada |
| CA004 | Ottawa | Ontario | K1N 5C8 | Canada |
| CA038 | Peterborough | Ontario | K9H 2P4 | Canada |
| CA009 | Toronto | Ontario | M3B 2W7 | Canada |
| CA037 | Windsor | Ontario | N8X 5A6 | Canada |
| CA005 | Beauport | Quebec | G1J 2G3 | Canada |
| CA023 | Greenfield Park | Quebec | J4V 2J2 | Canada |
| CA013 | Montreal | Quebec | H1T 2M4 | Canada |
| CA031 | Sherbrooke | Quebec | J1J 2B8 | Canada |
| CA012 | Sherbrooke | Quebec | J1J 3H5 | Canada |
| CA030 | Vanier | Quebec | G1M 2R9 | Canada |
| CA017 | Verdun | Quebec | H4H 1R3 | Canada |
| CA015 | Regina | Saskatchewan | S4T 1A5 | Canada |
| CA040 | Saskatoon | Saskatchewan | S7N 0W8 | Canada |
| CA043 | Kelowna | V1Y 3G8 | Canada |
| CA042 | Penticton | V2A 5C8 | Canada |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Memantine | 20 mg Oral Tablets Once Daily |
| BG001 | Placebo | Oral Tablets Once Daily |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| NPI: Baseline Total Score | The Neuropsychiatric Inventory (NPI) is a validated scale that assesses behavioural disturbances in patients with dementia. The 12 item version consists of 10 behavioural and 2 neurovegetative areas. It provides both a total score as well as scores for a number of sub-scales. The frequency, severity and caregiver distress for each domain are measured. The NPI is based upon responses obtained from the caregiver. The total score is from 0 to 144. A higher score reflects more frequency and severity of the disturbances. | Mean | Standard Deviation | Scores on a scale |
| ||||||||||||||
| SIB: Baseline Total Score | The Severe Impairment Battery (SIB) is a validated scale used to assess cognitive function in patients with moderate to severe dementia. Items are single words or one-step commands combined with gestures. Nine domains are assessed, and the total score is between 0 and 100. A lower total score reflects the loss of cognitive function. | Mean | Standard Deviation | Scores on a scale |
| ||||||||||||||
| CIBIC-plus: Baseline Severity Score | The Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus) is a global rating that is derived through an independent, comprehensive interview with the patient and caregiver by a rater who is barred from knowledge of all other psychometric test scores conducted as part of this protocol as well as from reported safety data. The rating is made on a 7-point scale ranging from "1 = marked improvement" to "7 = marked worsening". A score of "4" indicates no change. | Mean | Standard Deviation | Scores on a scale |
| ||||||||||||||
| ADCS-ADL - 19 items: Baseline Total Score | Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) - 19 items total score version for moderate to severe AD will measure patient's functioning. This battery of ADL questions is used here to measure the functional capabilities of patients with dementia. The inventory is done by interviewing a person in close contact with the patient and covers the most usual and consistent performance of the patient over the preceding 4 weeks. Total score is from 0 to 54. The higher score, the lower impairment. | Mean | Standard Deviation | Scores on a scale |
| ||||||||||||||
| CMAI - Long Form: Baseline Total Score | The Cohen-Mansfield Agitation Inventory (CMAI) - Long Form looks specifically at agitated behaviour in patients with cognitive impairment. It is a seven-point rating scale assessing the frequency of up to 29 agitated behaviours, ranging from "1 = Never" to "7 = Several times an hour". Rating is based on responses obtained from interviews with the caregiver. The total score ranges from 29 to 203, with a higher score reflecting more frequent behavioural disturbances. | Mean | Standard Deviation | Scores on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Efficacy of Memantine on Behavioural Symptoms in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the NPI - 12 Items Version Total Score. | Change from Baseline in Neuropsychiatric Inventory (NPI) total score. NPI is a validated scale that assesses behavioural disturbances in patients with dementia. The 12 item version consists of 10 behavioural and 2 neurovegetative areas. It provides both a total score as well as scores for a number of sub-scales. The frequency, severity and caregiver distress for each domain are measured. The NPI is based upon responses obtained from the caregiver. The total score is from 0 to 144. A higher score reflects more frequency and severity of the disturbances. | Full-analysis Set (FAS) - all randomised patients on current treatment with an acetylcholinesterase inhibitor (AChEI) who took at least one dose of investigational medicinal product (IMP) and had at least one post-baseline assessment on both co-primary efficacy variables. Last Observation Carried Forward (LOCF). | Posted | Mean | Standard Error | Scores on a scale | Baseline to Week 24 |
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| Primary | Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score. | Change from Baseline in Severe Impairment Battery (SIB) total score. SIB is a validated scale used to assess cognitive function in patients with moderate to severe dementia. Items are single words or one-step commands combined with gestures. Nine domains are assessed, and the total score is between 0 and 100. A lower total score reflects the loss of cognitive function. | FAS; LOCF | Posted | Mean | Standard Error | Scores on a scale | Baseline to Week 24 |
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| Secondary | Efficacy of Memantine on Global Condition Using CIBIC-plus. | Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus). Improvement evaluated with reference to Baseline. CIBIC-plus is a global rating that is derived through an independent, comprehensive interview with the patient and caregiver by a rater who is barred from knowledge of all other psychometric test scores conducted as part of this protocol as well as from reported safety data. The rating is made on a 7-point scale ranging from "1 = marked improvement" to "7 = marked worsening". A score of "4" indicates no change. | FAS; Observed Cases (OC). | Posted | Mean | Standard Error | Scores on a scale | Baseline to Week 24 |
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| Secondary | Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score. | Change from Baseline on the Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) 19-item version total score. ADCS-ADL- 19 items version for moderate to severe AD will measure patient's functioning. This battery of ADL questions is used here to measure the functional capabilities of patients with dementia. The inventory is done by interviewing a person in close contact with the patient and covers the most usual and consistent performance of the patient over the preceding 4 weeks. Total score is from 0 to 54. The higher score, the lower impairment. | FAS; OC | Posted | Mean | Standard Error | Scores on a scale | Baseline to Week 24 |
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| Secondary | Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score. | Change from Baseline on the Cohen-Mansfield Agitation Inventory (CMAI) - Long Form total score. CMAI - Long Form looks specifically at agitated behaviour in patients with cognitive impairment. It is a seven-point rating scale assessing the frequency of up to 29 agitated behaviours, ranging from "1 = Never" to "7 = Several times an hour". Rating is based on responses obtained from interviews with the caregiver. The total score ranges from 29 to 203, with a higher score reflecting more frequent behavioural disturbances. | FAS; OC | Posted | Mean | Standard Error | Scores on a scale | Baseline to Week 24 |
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Up to 28 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Memantine | 20 mg Oral Tablets Once Daily | 18 | 182 | 51 | 182 | ||
| EG001 | Placebo | Oral Tablets Once Daily | 11 | 187 | 35 | 187 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Bradyarrhythmia | Cardiac disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Gastric ulcer haemorrhage | Gastrointestinal disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Asthenia | General disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Local swelling | General disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Cholecystitis acute | Hepatobiliary disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Acute sinusitis | Infections and infestations | MedDRA Version 12.1 | Non-systematic Assessment |
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| Bronchitis viral | Infections and infestations | MedDRA Version 12.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 12.1 | Non-systematic Assessment |
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| Respiratory tract infection bacterial | Infections and infestations | MedDRA Version 12.1 | Non-systematic Assessment |
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| Urinary tract infection enterococcal | Infections and infestations | MedDRA Version 12.1 | Non-systematic Assessment |
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| Urosepsis | Infections and infestations | MedDRA Version 12.1 | Non-systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA Version 12.1 | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA Version 12.1 | Non-systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA Version 12.1 | Non-systematic Assessment |
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| Intentional overdose | Injury, poisoning and procedural complications | MedDRA Version 12.1 | Non-systematic Assessment |
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| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA Version 12.1 | Non-systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA Version 12.1 | Non-systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 12.1 | Non-systematic Assessment |
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| Ataxia | Nervous system disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Convulsion | Nervous system disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Dementia alzheimer's type | Nervous system disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Aggression | Psychiatric disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Agitation | Psychiatric disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Delirium | Psychiatric disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Hallucination, auditory | Psychiatric disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Major depression | Psychiatric disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Personality disorder | Psychiatric disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Urinary retention | Renal and urinary disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Swelling face | Skin and subcutaneous tissue disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Social stay hospitalisation | Social circumstances | MedDRA Version 12.1 | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA Version 12.1 | Non-systematic Assessment |
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| Weight decreased | Investigations | MedDRA Version 12.1 | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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| Agitation | Psychiatric disorders | MedDRA Version 12.1 | Non-systematic Assessment |
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Long recruitment, premature termination, substantial protocol changes; baseline imbalances (concomitant medication and severity of agitation). Variability across sites in reported events frequency (50% of agitation reports from a single site)
Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and H. Lundbeck A/S. Manuscripts and abstracts must be sent to H. Lundbeck A/S at least one month prior to submission for publication or presentation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| H. Lundbeck A/S | H. Lundbeck A/S | +45 3630 1311 | LundbeckClinicalTrials@lundbeck.com |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D008559 | Memantine |
| ID | Term |
|---|---|
| D000547 | Amantadine |
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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| Male |
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