Trial Outcomes & Findings for A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease (NCT NCT00862940)
NCT ID: NCT00862940
Last Updated: 2012-09-03
Results Overview
Measures direct changes in total brain volume per visit interval (screening to Week 4, 42, or 52 or from Week 4 to Week 42 or 52)
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
277 participants
Primary outcome timeframe
Baseline to 1 year
Results posted on
2012-09-03
Participant Flow
The patients were recruited from each investigator's outpatient clinic.
After a 3-week run-in period during which MRI scans were performed, the patients were randomised to either placebo or memantine and stratified according to AChEI treatment. Memantine-treated patients started with 5 mg/day and were uptitrated by 5 mg/day every week for 4 weeks. The target dose of 20 mg/day was administered from the start of Week 4.
Participant milestones
| Measure |
Memantine 10 mg Tablets Twice Daily
|
Placebo Tablets Twice Daily
|
|---|---|---|
|
Overall Study
STARTED
|
133
|
144
|
|
Overall Study
COMPLETED
|
103
|
114
|
|
Overall Study
NOT COMPLETED
|
30
|
30
|
Reasons for withdrawal
| Measure |
Memantine 10 mg Tablets Twice Daily
|
Placebo Tablets Twice Daily
|
|---|---|---|
|
Overall Study
Adverse Event
|
15
|
12
|
|
Overall Study
Lack of Efficacy
|
1
|
3
|
|
Overall Study
Protocol Violation
|
2
|
5
|
|
Overall Study
Withdrawal by Subject
|
4
|
6
|
|
Overall Study
Non-compliance
|
4
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Administrative or other reason(s)
|
4
|
3
|
Baseline Characteristics
A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Memantine 10 mg Tablets Twice Daily
n=133 Participants
|
Placebo Tablets Twice Daily
n=144 Participants
|
Total
n=277 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
73.7 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
74.4 years
STANDARD_DEVIATION 7.7 • n=7 Participants
|
74.1 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
83 Participants
n=5 Participants
|
75 Participants
n=7 Participants
|
158 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
50 Participants
n=5 Participants
|
69 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
|
Controlled Oral Word Association Test (COWAT): Baseline Efficacy Scores
|
19.7 Number of words
STANDARD_DEVIATION 10.3 • n=5 Participants
|
19.2 Number of words
STANDARD_DEVIATION 8.8 • n=7 Participants
|
19.4 Number of words
STANDARD_DEVIATION 9.6 • n=5 Participants
|
|
Category Fluency Test (CFT): Baseline Efficacy Scores
|
13.5 Number of words
STANDARD_DEVIATION 5.8 • n=5 Participants
|
13.3 Number of words
STANDARD_DEVIATION 5.9 • n=7 Participants
|
13.4 Number of words
STANDARD_DEVIATION 5.9 • n=5 Participants
|
|
ADAS-cog-Orientation Test (ADAS-cog-OT): Baseline Efficacy Scores
|
4.2 Points
STANDARD_DEVIATION 1.6 • n=5 Participants
|
4.0 Points
STANDARD_DEVIATION 1.7 • n=7 Participants
|
4.1 Points
STANDARD_DEVIATION 1.7 • n=5 Participants
|
|
Stroop Interference Test - Incongruent (SIT-I): Baseline Efficacy Scores
|
170.3 Seconds
STANDARD_DEVIATION 60.4 • n=5 Participants
|
176.4 Seconds
STANDARD_DEVIATION 56.7 • n=7 Participants
|
173.4 Seconds
STANDARD_DEVIATION 58.5 • n=5 Participants
|
|
Stroop Interference Test - Congruent (SIT-C): Baseline Efficacy Scores
|
70.5 Seconds
STANDARD_DEVIATION 49.1 • n=5 Participants
|
68.8 Seconds
STANDARD_DEVIATION 41.7 • n=7 Participants
|
69.6 Seconds
STANDARD_DEVIATION 45.4 • n=5 Participants
|
|
Mini Mental State Examination (MMSE): Baseline Efficacy Scores
|
16.9 Points
STANDARD_DEVIATION 2.4 • n=5 Participants
|
17.0 Points
STANDARD_DEVIATION 2.4 • n=7 Participants
|
16.9 Points
STANDARD_DEVIATION 2.4 • n=5 Participants
|
|
Neuropsychiatric Inventory (NPI): Baseline Efficacy Scores
|
13.1 Points
STANDARD_DEVIATION 12.8 • n=5 Participants
|
12.8 Points
STANDARD_DEVIATION 12.4 • n=7 Participants
|
13.0 Points
STANDARD_DEVIATION 12.6 • n=5 Participants
|
|
Magnetic Resonance Imaging (MRI) Descriptives
Total Brain Volume (TBV)
|
957.9 mL; mm^3
STANDARD_DEVIATION 103.3 • n=5 Participants
|
968.9 mL; mm^3
STANDARD_DEVIATION 108.3 • n=7 Participants
|
963.6 mL; mm^3
STANDARD_DEVIATION 105.8 • n=5 Participants
|
|
Magnetic Resonance Imaging (MRI) Descriptives
Hippocampal Volume (HCV)
|
5063.0 mL; mm^3
STANDARD_DEVIATION 1014.3 • n=5 Participants
|
5107.6 mL; mm^3
STANDARD_DEVIATION 836.7 • n=7 Participants
|
5086.1 mL; mm^3
STANDARD_DEVIATION 924.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 1 yearPopulation: FAS-MRI: Full-analysis set for all patients in the all-patients-treated set (APTS) who had at least one valid MRI scan \>=6 months after initiation of investigational medicinal product (IMP). The FAS (full analysis set, efficacy set) replaces the intention-to-treat (ITT) concept used in older terminology.
Measures direct changes in total brain volume per visit interval (screening to Week 4, 42, or 52 or from Week 4 to Week 42 or 52)
Outcome measures
| Measure |
Memantine 10 mg Tablets Twice Daily
n=110 Participants
|
Placebo Tablets Twice Daily
n=118 Participants
|
|---|---|---|
|
Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)
|
15.24 mL/year
Standard Error 0.97
|
15.32 mL/year
Standard Error 0.91
|
SECONDARY outcome
Timeframe: Baseline to 1 yearPopulation: FAS-MRI
Estimated mean changes in total HCV
Outcome measures
| Measure |
Memantine 10 mg Tablets Twice Daily
n=95 Participants
|
Placebo Tablets Twice Daily
n=109 Participants
|
|---|---|---|
|
Changes in Total Hippocampal Volume (HCV)
|
-218 mm^3/year
Standard Deviation 182
|
-220 mm^3/year
Standard Deviation 171
|
SECONDARY outcome
Timeframe: Baseline to 1 yearPopulation: FAS, observed cases (OC)
Adjusted mean change from baseline on cognitive and behavioural scores. COWAT: Verbal fluency test. The patient was asked to, during 1 minute, generate as many words as possible beginning with three pre-specified letters. The total score was calculated as the sum of acceptable words generated, with higher scores indicating lower cognitive impairment
Outcome measures
| Measure |
Memantine 10 mg Tablets Twice Daily
n=106 Participants
|
Placebo Tablets Twice Daily
n=114 Participants
|
|---|---|---|
|
Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score
|
0.78 Scale scores
Standard Error 0.71
|
-0.90 Scale scores
Standard Error 0.69
|
SECONDARY outcome
Timeframe: Baseline to 1 yearPopulation: FAS, OC
Adjusted mean change from baseline on cognitive and behavioural scores. MMSE: Brief, structured examination of mental status that assesses orientation, memory, attention, naming, comprehension, and praxis. The range is 0 to 30, with a lower score indicating a worse mental state
Outcome measures
| Measure |
Memantine 10 mg Tablets Twice Daily
n=108 Participants
|
Placebo Tablets Twice Daily
n=114 Participants
|
|---|---|---|
|
Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score
|
-0.50 Scale scores
Standard Error 0.45
|
-0.74 Scale scores
Standard Error 0.44
|
Adverse Events
Memantine 10 mg Tablets Twice Daily
Serious events: 17 serious events
Other events: 46 other events
Deaths: 0 deaths
Placebo Tablets Twice Daily
Serious events: 20 serious events
Other events: 36 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Memantine 10 mg Tablets Twice Daily
n=133 participants at risk
|
Placebo Tablets Twice Daily
n=144 participants at risk
|
|---|---|---|
|
Psychiatric disorders
Abnormal behaviour
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Psychiatric disorders
Agitation
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Anaemia
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Vascular disorders
Aortic aneurysm rupture
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Cardiac disorders
Atrial fibrillation
|
2.3%
3/133 • Number of events 5 • 1 year
|
0.00%
0/144 • 1 year
|
|
Nervous system disorders
Balance disorder
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia [gs]
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Infections and infestations
Bronchitis
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Cardiac disorders
Cardiac failure
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Nervous system disorders
Cerebral infarction
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Nervous system disorders
Cerebrovascular accident
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Vascular disorders
Circulatory collapse
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Injury, poisoning and procedural complications
Contusion
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Nervous system disorders
Convulsion
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Psychiatric disorders
Delirium
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Psychiatric disorders
Delusion
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Nervous system disorders
Dementia
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Psychiatric disorders
Disorientation
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Gastrointestinal disorders
Diverticulum intestinal haemorrhagic
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Injury, poisoning and procedural complications
Fall
|
3.0%
4/133 • Number of events 4 • 1 year
|
5.6%
8/144 • Number of events 9 • 1 year
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/133 • 1 year
|
2.1%
3/144 • Number of events 3 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal cancer metastatic
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Injury, poisoning and procedural complications
Gastrointestinal stoma complication
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Psychiatric disorders
Hallucination
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Vascular disorders
Hypotension
|
0.00%
0/133 • 1 year
|
1.4%
2/144 • Number of events 2 • 1 year
|
|
Psychiatric disorders
Insomnia
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Surgical and medical procedures
Knee arthroplasty
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Nervous system disorders
Lacunar infarction
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Surgical and medical procedures
Pacemaker generated rhythm
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Psychiatric disorders
Paranoia
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Nervous system disorders
Partial seizures
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer [gs]
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Cardiac disorders
Sick sinus syndrome
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Cardiac disorders
Sinoatrial block
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Social circumstances
Social stay hospitalisation
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Nervous system disorders
Somnolence
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Nervous system disorders
Syncope
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
|
Nervous system disorders
Transient ischaemic attack
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/133 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
0.75%
1/133 • Number of events 1 • 1 year
|
0.00%
0/144 • 1 year
|
Other adverse events
| Measure |
Memantine 10 mg Tablets Twice Daily
n=133 participants at risk
|
Placebo Tablets Twice Daily
n=144 participants at risk
|
|---|---|---|
|
Psychiatric disorders
Agitation
|
5.3%
7/133 • Number of events 7 • 1 year
|
0.69%
1/144 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Diarrhoea
|
3.0%
4/133 • Number of events 5 • 1 year
|
6.9%
10/144 • Number of events 11 • 1 year
|
|
Nervous system disorders
Dizziness
|
8.3%
11/133 • Number of events 11 • 1 year
|
2.8%
4/144 • Number of events 8 • 1 year
|
|
Injury, poisoning and procedural complications
Fall
|
6.0%
8/133 • Number of events 9 • 1 year
|
6.2%
9/144 • Number of events 10 • 1 year
|
|
Nervous system disorders
Headache
|
6.8%
9/133 • Number of events 11 • 1 year
|
4.9%
7/144 • Number of events 8 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
5.3%
7/133 • Number of events 8 • 1 year
|
3.5%
5/144 • Number of events 8 • 1 year
|
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