ELND005 in Patients With Mild to Moderate Alzheimer's Disease

This study has been completed.
Sponsor:
Collaborator:
Transition Therapeutics
Information provided by (Responsible Party):
Elan Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00568776
First received: December 4, 2007
Last updated: March 1, 2012
Last verified: March 2012
Results First Received: September 27, 2011  
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: Alzheimer Disease
Interventions: Drug: Placebo Control
Drug: ELND005

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Participant Flow:   Overall Study
    Placebo BID     ELND005 250 mg BID     ELND005 1000 mg BID     ELND005 2000 mg BID  
STARTED     83 [1]   88 [2]   89 [3]   91 [4]
COMPLETED     53     52     15     19  
NOT COMPLETED     30     36     74     72  
Adverse Event                 8                 8                 10                 8  
Death                 0                 1                 4                 3  
Physician Decision                 0                 2                 0                 0  
Lack of Efficacy                 2                 2                 2                 4  
Lost to Follow-up                 1                 1                 1                 1  
Protocol Violation                 1                 0                 1                 1  
Withdrawal by Subject                 13                 15                 13                 7  
Loss of Caregiver                 0                 2                 1                 2  
Sponsor Decision                 2                 2                 41                 42  
Miscellaeneous                 3                 3                 1                 4  
[1] One randomized patient withdrew consent and did not receive placebo
[2] One randomized patient withdrew consent and did not receive ELND005 250 mg BID
[3] 41 patients withdrawn per interim safety review (sponsors decision); excluded in efficacy analysis.
[4] 42 patients withdrawn per interim safety review (sponsors decision); excluded in efficacy analysis.



  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 BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks
Total Total of all reporting groups

Baseline Measures
    Placebo BID     ELND005 250 mg BID     ELND005 1000 mg BID     ELND005 2000 mg BID     Total  
Number of Participants  
[units: participants]
  83     88     89     91     351  
Age  
[units: years]
Mean ± Standard Deviation
  73.4  ± 7.83     73.4  ± 7.26     73.4  ± 7.56     72.2  ± 8.20     73.1  ± 7.7  
Gender  
[units: patients]
         
Female     47     51     48     51     197  
Male     36     37     41     40     154  
Region of Enrollment  
[units: patients]
         
United States     68     75     71     75     289  
Canada     15     13     18     16     62  



  Outcome Measures
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1.  Primary:   Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]

2.  Primary:   Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Per Protocol Set; PPS)   [ Time Frame: Baseline and 78 weeks ]

3.  Primary:   Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]

4.  Primary:   Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Per Protocol Set; PPS)   [ Time Frame: Baseline and 78 weeks ]

5.  Secondary:   Change in Alzheimer‘s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) Score From Baseline to Week 78 (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]

6.  Secondary:   Change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) Score From Baseline to Week 78 (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]

7.  Secondary:   Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Measure Description The NPI is used to obtain information on the presence of severity of neuropsychological symptoms, and was specifically designed for use in Alzheimer's disease subjects. The scale consists of 12 items with each item having outcomes from 0 to 12; hence the total score ranges from 0 to 144. Higher scores suggest greater psychiatric impairment.
Time Frame Baseline and 78 weeks  
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.
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and completed the baseline visit and at least one post-baseline visit.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Measured Values
    Placebo BID     ELND005 250 mg BID     ELND005 1000 mg BID     ELND005 2000 mg BID  
Number of Participants Analyzed  
[units: participants]
  82     84     0     0  
Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS)  
[units: Scores on a Scale]
Mean ± Standard Error
  -6.132  ± 1.851     -5.116  ± 1.814          


Statistical Analysis 1 for Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Groups [1] Placebo BID vs. ELND005 250 mg BID
Method [2] Mixed Models Analysis
P Value [3] 0.65
Mean Difference (Final Values) [4] 1.02
Standard Error of the mean ± 2.24
95% Confidence Interval ( -3.43 to 5.46 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[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.
[4] Other relevant estimation information:
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  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
The two high dose groups of ELND005 were discontinued before study end, so the efficacy analysis was based only on placebo and ELND005 250 mg bid groups.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Executive Vice President of Global Development and Chief Medical Officer
Organization: Elan Pharmaceuticals, Inc.
phone: 650 877 0900


No publications provided


Responsible Party: Elan Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00568776     History of Changes
Other Study ID Numbers: ELND005-AD201
Study First Received: December 4, 2007
Results First Received: September 27, 2011
Last Updated: March 1, 2012
Health Authority: United States: Food and Drug Administration