A Study of the Safety and Efficacy of Memantine in Moderate to Severe Alzheimer's Disease

This study has been completed.
Sponsor:
Information provided by:
Forest Laboratories
ClinicalTrials.gov Identifier:
NCT00322153
First received: May 3, 2006
Last updated: August 25, 2010
Last verified: August 2010
Results First Received: July 20, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Dementia of the Alzheimer's Type
Interventions: Drug: memantine ER
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The recruitment period was from May 20, 2005 to April 18th, 2007 at 83 study centers in four countries (23 in Argentina, 11 in Chile, 11 in Mexico, and 38 in the US)

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Study consisted of 1-2 weeks single-blind placebo treatment followed by 24 weeks double-blind treatment. At the end of single-blind placebo treatment, patients meeting entry criteria were randomized (1:1) to 1 of 2 double-blind treatment groups receiving memantine or placebo.

Reporting Groups
  Description
Placebo Matching placebo oral administration once daily for 24 weeks.
Memantine ER 28mg once daily oral administration for 24 weeks.

Participant Flow:   Overall Study
    Placebo     Memantine ER  
STARTED     335 [1]   342 [2]
SAFETY POPULATION     335 [3]   341 [4]
COMPLETED     272     273  
NOT COMPLETED     63     69  
Adverse Event                 21                 34  
Protocol Violation                 6                 14  
Withdrawal by Subject                 18                 10  
Lack of Efficacy                 8                 3  
Lost to Follow-up                 5                 4  
Withdrawn for other reasons                 5                 4  
[1] Randomized to placebo
[2] Randomized to Memantine ER
[3] Safety population defined as all patients who took at least one dose of double-blind study drug.
[4] Safety population: one patient was randomized but did not receive double-blind study drug.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Matching placebo oral administration once daily for 24 weeks.
Memantine ER 28mg once daily oral administration for 24 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo     Memantine ER     Total  
Number of Participants  
[units: participants]
  335     341     676  
Age, Customized  
[units: participants]
     
<= 64 years     26     34     60  
65-74 years     79     85     164  
75-84 years     179     176     355  
>= 85 years     51     46     97  
Age  
[units: years]
Mean ± Standard Deviation
  76.8  ± 7.76     76.2  ± 8.35     76.5  ± 8.07  
Gender  
[units: participants]
     
Female     243     244     487  
Male     92     97     189  
Region of Enrollment  
[units: participants]
     
United States     85     93     178  
Argentina     158     153     311  
Chile     44     46     90  
Mexico     48     49     97  



  Outcome Measures
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1.  Primary:   Change From Baseline in Severe Impairment Battery (SIB) at Week 24 (LOCF)   [ Time Frame: Baseline to week 24 ]

2.  Primary:   Clinician’s Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF)   [ Time Frame: Week 24 ]

3.  Secondary:   Change From Baseline in the 19-Item Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19) Scale at Week 24 (LOCF)   [ Time Frame: Baseline to week 24 ]


  Serious Adverse Events
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Time Frame Occurring on or after the date of the first dose of double-blind study medication and within 30 days of the date of last dose of double-blind study medication.
Additional Description No text entered.

Reporting Groups
  Description
Placebo Matching placebo oral administration once daily for 24 weeks.
Memantine ER 28mg once daily oral administration for 24 weeks.

Serious Adverse Events
    Placebo     Memantine ER  
Total, serious adverse events      
# participants affected / at risk     21/335 (6.27%)     28/341 (8.21%)  
Cardiac disorders      
Atrioventricular block complete † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Bradycardia † 1    
# participants affected / at risk     1/335 (0.30%)     1/341 (0.29%)  
Sinus bradycardia † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Cardiac Arrest † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Cardiac Failure Congestive † 1    
# participants affected / at risk     3/335 (0.90%)     0/341 (0.00%)  
Cardio-respiratory arrest † 1    
# participants affected / at risk     2/335 (0.60%)     0/341 (0.00%)  
Myocardial infarction † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Gastrointestinal disorders      
Diarrhoea † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Rectal Prolapse † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Toothache † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Vomiting † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
General disorders      
Chest Pain † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
General physical health deterioration † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Drowning † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Infections and infestations      
Pneumonia † 1    
# participants affected / at risk     0/335 (0.00%)     2/341 (0.59%)  
Urinary tract infection † 1    
# participants affected / at risk     3/335 (0.90%)     2/341 (0.59%)  
Lobar Pneumonia † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Meningitis bacterial † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Bacteraemia † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Herpes zoster † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Injury, poisoning and procedural complications      
Fall † 1    
# participants affected / at risk     5/335 (1.49%)     2/341 (0.59%)  
Pneumothorax traumatic † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Skin laceration † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Spinal compression fracture † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Head Injury † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Hip fracture † 1    
# participants affected / at risk     3/335 (0.90%)     0/341 (0.00%)  
Traumatic brain injury † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Investigations      
Anticoagulation drug level above therapeutic † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Metabolism and nutrition disorders      
Anorexia † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Hypoglycaemia † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Hypokalaemia † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Musculoskeletal and connective tissue disorders      
Back Pain † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Cholesteatoma † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Metastatic carcinoma of the bladder † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Renal neoplasm † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Prostate cancer † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Nervous system disorders      
Cerebrovascular accident † 1    
# participants affected / at risk     0/335 (0.00%)     2/341 (0.59%)  
Syncope † 1    
# participants affected / at risk     0/335 (0.00%)     2/341 (0.59%)  
Cerebral haemorrhage † 1    
# participants affected / at risk     1/335 (0.30%)     1/341 (0.29%)  
Dementia Alzheimer's type † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Facial paresis † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Ischaemic stroke † 1    
# participants affected / at risk     1/335 (0.30%)     1/341 (0.29%)  
Myoclonus † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Syncope vasovagal † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Transient ischaemic attack † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Convulsion † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Intracranial haematoma † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Psychiatric disorders      
Anxiety disorder due to a general medical condition † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Delusion † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Renal and urinary disorders      
Renal failure † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Urinary retention † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Pneumonia aspiration † 1    
# participants affected / at risk     1/335 (0.30%)     1/341 (0.29%)  
Respiratory arrest † 1    
# participants affected / at risk     1/335 (0.30%)     0/341 (0.00%)  
Skin and subcutaneous tissue disorders      
Excessive skin † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Surgical and medical procedures      
Proctocolectomy † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Vascular disorders      
Deep vein thrombosis † 1    
# participants affected / at risk     0/335 (0.00%)     1/341 (0.29%)  
Hypotension † 1    
# participants affected / at risk     1/335 (0.30%)     1/341 (0.29%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 10.1




  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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