Trial Outcomes & Findings for Safety and Tolerability of Memantine in Moderate to Severe Alzheimer's Disease (NCT NCT00857233)
NCT ID: NCT00857233
Last Updated: 2012-08-29
Results Overview
Overview of AEs
TERMINATED
PHASE3
297 participants
Baseline to Week 24
2012-08-29
Participant Flow
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.
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.
Participant milestones
| Measure |
Memantine
20 mg Oral Tablets Once Daily
|
|---|---|
|
Overall Study
STARTED
|
297
|
|
Overall Study
COMPLETED
|
242
|
|
Overall Study
NOT COMPLETED
|
55
|
Reasons for withdrawal
| Measure |
Memantine
20 mg Oral Tablets Once Daily
|
|---|---|
|
Overall Study
Adverse Event
|
24
|
|
Overall Study
Lack of Efficacy
|
1
|
|
Overall Study
Non-compliance
|
1
|
|
Overall Study
Withdrawal of Consent
|
9
|
|
Overall Study
Lost to Follow-up
|
4
|
|
Overall Study
Nursing Home Placement
|
14
|
|
Overall Study
Other Reasons
|
2
|
Baseline Characteristics
Safety and Tolerability of Memantine in Moderate to Severe Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Memantine
n=297 Participants
20 mg Oral Tablets Once Daily
|
|---|---|
|
Age Continuous
|
75 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
172 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
125 Participants
n=5 Participants
|
|
NPI: Baseline Total Score
|
22.32 Scores on a scale
STANDARD_DEVIATION 15.41 • n=5 Participants
|
|
SIB: Baseline Total Score
|
79.99 Scores on a Scale
STANDARD_DEVIATION 16.36 • n=5 Participants
|
|
CIBIC-plus: Baseline Severity Score
|
4.52 Scores on a scale
STANDARD_DEVIATION 0.85 • n=5 Participants
|
|
ADCS-ADL - 19 items: Baseline Total Score
|
33.43 Scores on a scale
STANDARD_DEVIATION 10.06 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 24Population: 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)
Overview of AEs
Outcome measures
| Measure |
Memantine
n=297 Participants
20 mg Oral Tablets Once Daily
|
|---|---|
|
Number of Patients With Adverse Events (AEs)
Patients with AEs
|
191 participants
|
|
Number of Patients With Adverse Events (AEs)
Patients with serious AEs (SAEs)
|
27 participants
|
|
Number of Patients With Adverse Events (AEs)
Patients with AEs Leading to Withdrawal
|
24 participants
|
|
Number of Patients With Adverse Events (AEs)
Patients with Baseline Events
|
1 participants
|
PRIMARY outcome
Timeframe: Baseline to Week 24Population: APTS
Outcome measures
| Measure |
Memantine
n=297 Participants
20 mg Oral Tablets Once Daily
|
|---|---|
|
Percentage of Patients Who Withdrew Due to Intolerance to Treatment
|
8.1 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: APTS; Observed cases (OC)
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.
Outcome measures
| Measure |
Memantine
n=247 Participants
20 mg Oral Tablets Once Daily
|
|---|---|
|
Long-term Efficacy of Memantine on Behavioural Symptoms Using the Neuropsychiatric Inventory (NPI) - 12 Items Version Total Score.
|
2.11 Scores on a scale
Standard Deviation 16.12
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: APTS; OC
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.
Outcome measures
| Measure |
Memantine
n=244 Participants
20 mg Oral Tablets Once Daily
|
|---|---|
|
Long-term Efficacy of Memantine on Cognition Using the Severe Impairment Battery (SIB) Total Score.
|
-5.60 Scores on a scale
Standard Deviation 9.81
|
SECONDARY outcome
Timeframe: Week 24Population: APTS; OC
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.
Outcome measures
| Measure |
Memantine
n=243 Participants
20 mg Oral Tablets Once Daily
|
|---|---|
|
Long-term Efficacy of Memantine on Global Condition Using the Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus).
|
4.75 Scores on a scale
Standard Deviation 1.14
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: APTS; OC
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.
Outcome measures
| Measure |
Memantine
n=247 Participants
20 mg Oral Tablets Once Daily
|
|---|---|
|
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
|
-4.16 Scores on a scale
Standard Deviation 6.45
|
Adverse Events
Memantine
Serious adverse events
| Measure |
Memantine
n=297 participants at risk
20 mg Oral Tablets Once Daily
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Cardiac disorders
Acute myocardial infarction
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Cardiac disorders
Bradycardia
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Cardiac disorders
Cardiac failure
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
General disorders
Asthenia
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Hepatobiliary disorders
Bile duct stone
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Infections and infestations
Gastroenteritis
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Infections and infestations
Pneumonia
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Infections and infestations
Scrotal infection
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Injury, poisoning and procedural complications
Acetabulum fracture
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Injury, poisoning and procedural complications
Fall
|
1.7%
5/297 • 24 weeks plus 30 days safety follow-up period
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.67%
2/297 • 24 weeks plus 30 days safety follow-up period
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Nervous system disorders
Dementia Alzheimer's type
|
0.67%
2/297 • 24 weeks plus 30 days safety follow-up period
|
|
Nervous system disorders
Dizziness
|
0.67%
2/297 • 24 weeks plus 30 days safety follow-up period
|
|
Nervous system disorders
Syncope
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Psychiatric disorders
Abnormal behaviour
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Psychiatric disorders
Aggression
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Psychiatric disorders
Hallucination
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Psychiatric disorders
Restlessness
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.34%
1/297 • 24 weeks plus 30 days safety follow-up period
|
|
Social circumstances
Social stay hospitalisation
|
1.0%
3/297 • 24 weeks plus 30 days safety follow-up period
|
Other adverse events
| Measure |
Memantine
n=297 participants at risk
20 mg Oral Tablets Once Daily
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
3.0%
9/297 • 24 weeks plus 30 days safety follow-up period
|
|
Gastrointestinal disorders
Diarrhoea
|
4.0%
12/297 • 24 weeks plus 30 days safety follow-up period
|
|
Gastrointestinal disorders
Nausea
|
3.4%
10/297 • 24 weeks plus 30 days safety follow-up period
|
|
General disorders
Gait disturbance
|
3.0%
9/297 • 24 weeks plus 30 days safety follow-up period
|
|
Injury, poisoning and procedural complications
Fall
|
5.1%
15/297 • 24 weeks plus 30 days safety follow-up period
|
|
Nervous system disorders
Dizziness
|
5.1%
15/297 • 24 weeks plus 30 days safety follow-up period
|
|
Nervous system disorders
Headache
|
3.4%
10/297 • 24 weeks plus 30 days safety follow-up period
|
|
Psychiatric disorders
Agitation
|
6.1%
18/297 • 24 weeks plus 30 days safety follow-up period
|
|
Psychiatric disorders
Confusional state
|
3.4%
10/297 • 24 weeks plus 30 days safety follow-up period
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER