Trial Outcomes & Findings for Efficacy and Safety of Memantine in Moderate to Severe Alzheimer's Disease (NCT NCT00857649)
NCT ID: NCT00857649
Last Updated: 2013-12-05
Results Overview
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.
TERMINATED
PHASE3
369 participants
Baseline to Week 24
2013-12-05
Participant Flow
The patients were recruited from the investigators' outpatient clinics.
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.
Participant milestones
| Measure |
Memantine
20 mg Oral Tablets Once Daily
|
Placebo
Oral Tablets Once Daily
|
|---|---|---|
|
Overall Study
STARTED
|
182
|
187
|
|
Overall Study
COMPLETED
|
151
|
155
|
|
Overall Study
NOT COMPLETED
|
31
|
32
|
Reasons for withdrawal
| Measure |
Memantine
20 mg Oral Tablets Once Daily
|
Placebo
Oral Tablets Once Daily
|
|---|---|---|
|
Overall Study
Adverse Event
|
15
|
10
|
|
Overall Study
Non-compliance
|
1
|
1
|
|
Overall Study
Protocol Violation
|
2
|
2
|
|
Overall Study
Withdrawal of Consent
|
10
|
7
|
|
Overall Study
Nursing Home Placement
|
2
|
9
|
|
Overall Study
Other Reasons
|
1
|
3
|
Baseline Characteristics
Efficacy and Safety of Memantine in Moderate to Severe Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Memantine
n=182 Participants
20 mg Oral Tablets Once Daily
|
Placebo
n=187 Participants
Oral Tablets Once Daily
|
Total
n=369 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
74.7 years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
75.1 years
STANDARD_DEVIATION 6.9 • n=7 Participants
|
74.9 years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
105 Participants
n=5 Participants
|
110 Participants
n=7 Participants
|
215 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
77 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
154 Participants
n=5 Participants
|
|
NPI: Baseline Total Score
|
30.9 Scores on a scale
STANDARD_DEVIATION 14.8 • n=5 Participants
|
29.2 Scores on a scale
STANDARD_DEVIATION 13.3 • n=7 Participants
|
30.1 Scores on a scale
STANDARD_DEVIATION 14.0 • n=5 Participants
|
|
SIB: Baseline Total Score
|
82.3 Scores on a scale
STANDARD_DEVIATION 14.6 • n=5 Participants
|
82.0 Scores on a scale
STANDARD_DEVIATION 12.9 • n=7 Participants
|
82.1 Scores on a scale
STANDARD_DEVIATION 13.7 • n=5 Participants
|
|
CIBIC-plus: Baseline Severity Score
|
4.4 Scores on a scale
STANDARD_DEVIATION 0.9 • n=5 Participants
|
4.4 Scores on a scale
STANDARD_DEVIATION 0.9 • n=7 Participants
|
4.4 Scores on a scale
STANDARD_DEVIATION 0.9 • n=5 Participants
|
|
ADCS-ADL - 19 items: Baseline Total Score
|
35.3 Scores on a scale
STANDARD_DEVIATION 9.9 • n=5 Participants
|
36.4 Scores on a scale
STANDARD_DEVIATION 8.6 • n=7 Participants
|
35.8 Scores on a scale
STANDARD_DEVIATION 9.3 • n=5 Participants
|
|
CMAI - Long Form: Baseline Total Score
|
46.8 Scores on a scale
STANDARD_DEVIATION 10.9 • n=5 Participants
|
47.0 Scores on a scale
STANDARD_DEVIATION 10.9 • n=7 Participants
|
46.9 Scores on a scale
STANDARD_DEVIATION 10.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 24Population: 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).
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.
Outcome measures
| Measure |
Memantine
n=159 Participants
20 mg Oral Tablets Once Daily
|
Placebo
n=165 Participants
Oral Tablets Once Daily
|
|---|---|---|
|
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.
|
-3.90 Scores on a scale
Standard Error 1.24
|
-5.13 Scores on a scale
Standard Error 1.23
|
PRIMARY outcome
Timeframe: Baseline to Week 24Population: FAS; LOCF
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.
Outcome measures
| Measure |
Memantine
n=159 Participants
20 mg Oral Tablets Once Daily
|
Placebo
n=165 Participants
Oral Tablets Once Daily
|
|---|---|---|
|
Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score.
|
-2.34 Scores on a scale
Standard Error 0.76
|
-1.86 Scores on a scale
Standard Error 0.75
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: FAS; Observed Cases (OC).
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.
Outcome measures
| Measure |
Memantine
n=135 Participants
20 mg Oral Tablets Once Daily
|
Placebo
n=140 Participants
Oral Tablets Once Daily
|
|---|---|---|
|
Efficacy of Memantine on Global Condition Using CIBIC-plus.
|
4.68 Scores on a scale
Standard Error 0.11
|
4.63 Scores on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: FAS; OC
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.
Outcome measures
| Measure |
Memantine
n=136 Participants
20 mg Oral Tablets Once Daily
|
Placebo
n=140 Participants
Oral Tablets Once Daily
|
|---|---|---|
|
Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score.
|
-4.36 Scores on a scale
Standard Error 0.67
|
-2.56 Scores on a scale
Standard Error 0.65
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: FAS; OC
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.
Outcome measures
| Measure |
Memantine
n=134 Participants
20 mg Oral Tablets Once Daily
|
Placebo
n=139 Participants
Oral Tablets Once Daily
|
|---|---|---|
|
Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score.
|
-0.26 Scores on a scale
Standard Error 0.79
|
-1.16 Scores on a scale
Standard Error 0.79
|
Adverse Events
Memantine
Placebo
Serious adverse events
| Measure |
Memantine
n=182 participants at risk
20 mg Oral Tablets Once Daily
|
Placebo
n=187 participants at risk
Oral Tablets Once Daily
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/182 • Up to 28 weeks
|
1.1%
2/187 • Up to 28 weeks
|
|
Cardiac disorders
Atrial fibrillation
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Cardiac disorders
Bradyarrhythmia
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
General disorders
Asthenia
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
General disorders
Local swelling
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Infections and infestations
Acute sinusitis
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Infections and infestations
Bronchitis viral
|
0.00%
0/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Infections and infestations
Pneumonia
|
0.00%
0/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Infections and infestations
Respiratory tract infection bacterial
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Infections and infestations
Urinary tract infection enterococcal
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Infections and infestations
Urosepsis
|
1.1%
2/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Infections and infestations
Viral infection
|
0.00%
0/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
1.1%
2/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.55%
1/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Nervous system disorders
Ataxia
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Nervous system disorders
Cerebrovascular accident
|
0.55%
1/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Nervous system disorders
Convulsion
|
0.00%
0/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Nervous system disorders
Dementia alzheimer's type
|
0.00%
0/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Psychiatric disorders
Aggression
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Psychiatric disorders
Agitation
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Psychiatric disorders
Confusional state
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Psychiatric disorders
Delirium
|
0.00%
0/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Psychiatric disorders
Hallucination, auditory
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Psychiatric disorders
Major depression
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Psychiatric disorders
Personality disorder
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
|
Social circumstances
Social stay hospitalisation
|
0.55%
1/182 • Up to 28 weeks
|
0.53%
1/187 • Up to 28 weeks
|
|
Vascular disorders
Hypertension
|
0.55%
1/182 • Up to 28 weeks
|
0.00%
0/187 • Up to 28 weeks
|
Other adverse events
| Measure |
Memantine
n=182 participants at risk
20 mg Oral Tablets Once Daily
|
Placebo
n=187 participants at risk
Oral Tablets Once Daily
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
2.2%
4/182 • Up to 28 weeks
|
5.9%
11/187 • Up to 28 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
10.4%
19/182 • Up to 28 weeks
|
4.3%
8/187 • Up to 28 weeks
|
|
Investigations
Weight decreased
|
6.0%
11/182 • Up to 28 weeks
|
2.7%
5/187 • Up to 28 weeks
|
|
Nervous system disorders
Somnolence
|
5.5%
10/182 • Up to 28 weeks
|
2.7%
5/187 • Up to 28 weeks
|
|
Psychiatric disorders
Agitation
|
8.2%
15/182 • Up to 28 weeks
|
3.7%
7/187 • Up to 28 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER