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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Withdrawn for other reasons                5                4 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 
Overall Participants Analyzed 
[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
  Show All Outcome Measures

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 ]
  Hide Outcome Measure 2

Measure Type Primary
Measure Title Clinician’s Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF)
Measure Description The CIBIC-Plus is a measure of an overall clinical effect and is based on a comprehensive evaluation at Baseline and later visits of four domains: general (overall clinical status), functional (including activities of daily living), cognitive, and behavioral. A skilled clinician interviews the patient, and includes information supplied by a knowledgeable caregiver. The CIBIC-Plus is a rating of the patient’s global status relative to Baseline, ranging from a score of 1, indicating “marked improvement” to a score of 4, indicating “no change” to a score of 7, indicating “marked worsening.”
Time Frame Week 24  
Safety Issue No  

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.
Primary efficacy analysis was based on the Intent-to-Treat (ITT) Population. The ITT Population was consisted of all patients in the Safety Population who completed at least one post-Baseline efficacy assessment in SIB or CIBIC-Plus. The last-observation-carried-forward approach was used to impute missing post-Baseline values.

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

Measured Values
   Placebo   Memantine ER 
Participants Analyzed 
[Units: Participants]
 328   333 
Clinician’s Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF) 
[Units: Units on a scale]
Mean (Standard Error)
 4.1  (0.07)   3.8  (0.07) 


Statistical Analysis 1 for Clinician’s Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) at Week 24 (LOCF)
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.008
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The co-primary efficacy parameter was CIBIC-Plus total score at week 24. Missing CIBIC-Plus total scores at Week 24 were imputed using the last-observation-carried-forward (LOCF) approach.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



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


  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
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  More Information