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
  Hide Participant Flow

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
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

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
  Show All Outcome Measures

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 ]


  Serious Adverse Events
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Time Frame Reported adverse events include events starting at or after Screening to Week 84
Additional Description For all adverse event (AE) summaries, if a patient had more than one AE within a preferred term the patient was counted only once, at the maximum severity and with the closest relationship to study drug. If a patient had more than one AE within a system organ class (SOC), the patient was similarly counted once when reporting results for that SOC.

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

Serious Adverse Events
    Placebo BID     ELND005 250 mg BID     ELND005 1000 mg BID     ELND005 2000 mg BID  
Total, serious adverse events          
# participants affected / at risk     11/83 (13.25%)     19/88 (21.59%)     20/89 (22.47%)     21/91 (23.08%)  
Blood and lymphatic system disorders          
Haemorrhagic Anaemia † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Cardiac disorders          
Angina Unstable † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Atrial Fribrillation † 1        
# participants affected / at risk     1/83 (1.20%)     1/88 (1.14%)     1/89 (1.12%)     1/91 (1.10%)  
Atrial Futter † 1        
# participants affected / at risk     1/83 (1.20%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Cardiac Arrest † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Cardiac Failure Congestive † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     2/91 (2.20%)  
Coronary Artery Occlusion † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Myocardial Infarction † 1        
# participants affected / at risk     1/83 (1.20%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Supraventricular Tachycardia † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Eye disorders          
Glaucoma † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Retinal Vein Occlusion † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Vitreous Haemorrhage † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Gastrointestinal disorders          
Gastric Ulcer Haemorrhage † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Gastritis † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Gastritis Hemorrhagic † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Hemorrhoidal hemorrhage † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Pancreatitis † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Small Intestinal Obstruction † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
General disorders          
Hypothermia † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Sudden Death † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     1/91 (1.10%)  
Hepatobiliary disorders          
Cholecystitis † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Infections and infestations          
Arthritis Bacterial † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Bacterial Sepsis † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Kidney Infection † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Pneumonia † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     2/89 (2.25%)     3/91 (3.30%)  
Pneumonia Bacterial † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Staphylococcal Infection † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Urinary Tract Infection † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     3/91 (3.30%)  
Urosepsis † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Viral Infection † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Injury, poisoning and procedural complications          
Accidental Overdose † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Compression Fracture † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Contusion † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Fall † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     1/91 (1.10%)  
Hip Fracture † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Jaw Fracture † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Laceration † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Multiple Fractures † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Post Procedural Haematoma † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Postoperative Ileus † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Subdural Hematoma † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Investigations          
Electrocardiogram Change † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Hepatic Enzyme Increased † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Lipase Increased † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Metabolism and nutrition disorders          
Dehydration † 1        
# participants affected / at risk     2/83 (2.41%)     1/88 (1.14%)     2/89 (2.25%)     2/91 (2.20%)  
Failure to Thrive † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Hyperglycemia † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Musculoskeletal and connective tissue disorders          
Mobility Decreased † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Basal Cell Carcinoma † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Breast Cancer † 1        
# participants affected / at risk     0/83 (0.00%)     3/88 (3.41%)     0/89 (0.00%)     0/91 (0.00%)  
Breast Cancer In Situ † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Colon Cancer † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Colorectal Cancer † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Renal Cell Carcinoma † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     2/91 (2.20%)  
Squamous Cell Carcinoma † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Squamous Cell Carcinoma of Skin † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Nervous system disorders          
Carotid Artery Occlusion † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Cerebral Hemorrhage † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Cerebrovascular Accident † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     1/91 (1.10%)  
Dementia Alzheimer‘s Type † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Dizziness † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Encephalopathy † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Haemorrhagic Stroke † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Ischaemic Cerebral Infarction † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Syncope † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     1/91 (1.10%)  
Transient Ischaemic Attack † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Psychiatric disorders          
Acute Psychosis † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     0/89 (0.00%)     1/91 (1.10%)  
Agitation † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     1/89 (1.12%)     0/91 (0.00%)  
Confusional State † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Delirium † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Mental Status Changes † 1        
# participants affected / at risk     1/83 (1.20%)     0/88 (0.00%)     0/89 (0.00%)     0/91 (0.00%)  
Psychotic Disorder † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     1/91 (1.10%)  
Renal and urinary disorders          
Renal Failure Acute † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     2/89 (2.25%)     0/91 (0.00%)  
Urinary Retention † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     0/91 (0.00%)  
Respiratory, thoracic and mediastinal disorders          
Pleural Effusion † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     2/89 (2.25%)     0/91 (0.00%)  
Pneumonia Aspiration † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     2/89 (2.25%)     0/91 (0.00%)  
Pneumothorax † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Pulmonary Embolism † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     1/91 (1.10%)  
Respiratory Failure † 1        
# participants affected / at risk     0/83 (0.00%)     0/88 (0.00%)     1/89 (1.12%)     1/91 (1.10%)  
Vascular disorders          
Aortic Thrombosis † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Deep Vein Thrombosis † 1        
# participants affected / at risk     0/83 (0.00%)     1/88 (1.14%)     0/89 (0.00%)     0/91 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, CTCAE (3.0)




  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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