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Please see explanation in the Detailed Description field.
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The primary objective of the study was to examine the safety and tolerability of memantine in outpatients with moderate to severe Alzheimer's Disease.
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.
The purpose of this 24-week open-label extension study was to collect additional long-term safety and tolerability data on memantine in patients who completed the lead-in double-blind placebo-controlled Study 10158.
In agreement with Health Canada the study was prematurely terminated due to recruitment difficulties in the lead-in Study 10158. Patients ongoing in the study when the decision to terminate was taken were allowed to complete it.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Memantine | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Memantine | Drug | 20 mg oral tablets once daily |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Adverse Events (AEs) | Overview of AEs | Baseline to Week 24 |
| Percentage of Patients Who Withdrew Due to Intolerance to Treatment | Baseline to Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Long-term Efficacy of Memantine on Behavioural Symptoms Using the Neuropsychiatric Inventory (NPI) - 12 Items Version Total Score. | Change from Baseline in the NPI total score. Analysed by descriptive methods only. 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. |
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Inclusion Criteria:
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 |
Placebo patients from Study 10158 were uptitrated in weekly increments of 5 mg over a 4-week, double-blind period. Target dose of 20 mg/day was reached at the start of the 4th week and maintained for the rest of the study. Memantine patients in Study 10158 continued on 20 mg/day. From the end of Week 4, the study was open-label.
This was an interventional, multi-centre, open-label, fixed-dose extension study to Study 10158. The Baseline visit in Study 10252 was scheduled to occur at the same time as the Week 24 Visit in Study 10158.
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| ID | Title | Description |
|---|---|---|
| FG000 | Memantine | 20 mg Oral Tablets Once Daily |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Baseline and Week 24 |
| Long-term Efficacy of Memantine on Cognition Using the Severe Impairment Battery (SIB) Total Score. | Change from Baseline in the SIB total score. Analysed by descriptive methods only. 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 and Week 24 |
| Long-term Efficacy of Memantine on Global Condition Using the Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus). | CIBIC-plus. Improvement evaluated with reference to Baseline. Analysed by descriptive methods only. 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. | Week 24 |
| Long-term Efficacy of Memantine on Functioning Using the Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) 19-item Version Total Score | Change from Baseline on the ADCS-ADL 19-item version total score. Analysed by descriptive methods only. 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 and Week 24 |
| Kelowna |
| British Columbia |
| V1W 4V5 |
| Canada |
| CA043 | Kelowna | British Columbia | V1Y 3G8 | Canada |
| CA042 | Penticton | British Columbia | V2A 5C8 | Canada |
| CA034 | Winnipeg | Manitoba | R3M 0X9 | Canada |
| CA022 | Saint John | New Brunswick | 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 |
| CA005 | Beauport | Quebec | G1J 2G3 | Canada |
| CA023 | Greenfield Park | Quebec | J4V 2J2 | Canada |
| CA013 | Montreal | Quebec | H1T 2M4 | 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 |
| CA044 | Chatham | N7L 1B7 | Canada |
| CA007 | Kentville | B4N 4K9 | Canada |
| CA046 | Kentville | B4N 4K9 | Canada |
| CA001 | Kingston | K7L 2V7 | Canada |
| CA003 | London | N6A 4V2 | Canada |
| CA002 | London | N6C5J1 | Canada |
| CA016 | Moncton | E1C 4B7 | Canada |
| CA024 | Montreal | H2X 3J4 | Canada |
| CA014 | Montreal | H3T 1E2 | Canada |
| CA011 | Montreal | H4H 1R3 | Canada |
| CA031 | Sherbrooke | J1J 2B8 | Canada |
| CA006 | Toronto | M6M 3Z5 | Canada |
| CA037 | Windsor | N8X 5A6 | Canada |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Memantine | 20 mg Oral Tablets Once Daily |
| 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 | 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 | The Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) 19-item version total score 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 |
|
| 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 | Number of Patients With Adverse Events (AEs) | Overview of AEs | Completers from lead-in study 10158 were eligible for this open-label extension study. We analysed the All-patients-treated Set (APTS) - all patients who took at least one dose of investigational medicinal product (IMP) | Posted | Number | participants | Baseline to Week 24 |
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| Secondary | Long-term Efficacy of Memantine on Behavioural Symptoms Using the Neuropsychiatric Inventory (NPI) - 12 Items Version Total Score. | Change from Baseline in the NPI total score. Analysed by descriptive methods only. 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. | APTS; Observed cases (OC) | Posted | Mean | Standard Deviation | Scores on a scale | Baseline and Week 24 |
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| Secondary | Long-term Efficacy of Memantine on Cognition Using the Severe Impairment Battery (SIB) Total Score. | Change from Baseline in the SIB total score. Analysed by descriptive methods only. 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. | APTS; OC | Posted | Mean | Standard Deviation | Scores on a scale | Baseline and Week 24 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Long-term Efficacy of Memantine on Global Condition Using the Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus). | CIBIC-plus. Improvement evaluated with reference to Baseline. Analysed by descriptive methods only. 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. | APTS; OC | Posted | Mean | Standard Deviation | Scores on a scale | Week 24 |
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| Secondary | Long-term Efficacy of Memantine on Functioning Using the Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) 19-item Version Total Score | Change from Baseline on the ADCS-ADL 19-item version total score. Analysed by descriptive methods only. 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. | APTS; OC | Posted | Mean | Standard Deviation | Scores on a scale | Baseline and Week 24 |
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| Primary | Percentage of Patients Who Withdrew Due to Intolerance to Treatment | APTS | Posted | Number | percentage of participants | Baseline to Week 24 |
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24 weeks plus 30 days safety follow-up period
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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 | 27 | 297 | 85 | 297 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 12.1 | Non-systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders |
| |||
| Bradycardia | Cardiac disorders |
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| Cardiac failure | Cardiac disorders |
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| Supraventricular tachycardia | Cardiac disorders |
| |||
| Asthenia | General disorders |
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| Bile duct stone | Hepatobiliary disorders |
| |||
| Gastroenteritis | Infections and infestations |
| |||
| Pneumonia | Infections and infestations |
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| Scrotal infection | Infections and infestations |
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| Urinary tract infection bacterial | Infections and infestations |
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| Acetabulum fracture | Injury, poisoning and procedural complications |
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| Fall | Injury, poisoning and procedural complications |
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| Hip fracture | Injury, poisoning and procedural complications |
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| Lumbar vertebral fracture | Injury, poisoning and procedural complications |
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| Upper limb fracture | Injury, poisoning and procedural complications |
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| Muscular weakness | Musculoskeletal and connective tissue disorders |
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| Oesophageal carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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| Dementia Alzheimer's type | Nervous system disorders |
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| Dizziness | Nervous system disorders |
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| Syncope | Nervous system disorders |
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| Abnormal behaviour | Psychiatric disorders |
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| Aggression | Psychiatric disorders |
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| Hallucination | Psychiatric disorders |
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| Restlessness | Psychiatric disorders |
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| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders |
| |||
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders |
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| Social stay hospitalisation | Social circumstances |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders |
| |||
| Diarrhoea | Gastrointestinal disorders |
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| Nausea | Gastrointestinal disorders |
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| Gait disturbance | General disorders |
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| Fall | Injury, poisoning and procedural complications |
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| Dizziness | Nervous system disorders |
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| Headache | Nervous system disorders |
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| Agitation | Psychiatric disorders |
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| Confusional state | Psychiatric disorders |
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Long recruitment, premature termination.
The main publication has to be published before any sub-publications. Order of authors has to be established. 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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| Title | Measurements |
|---|---|
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| Patients with Baseline Events |
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