ELND005 in Patients With Mild to Moderate Alzheimer's Disease

• Sponsor: OPKO Health, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00568776
• Collaborator: (none)
• Enrollment: 353
• Locations: 62
• Arms: 4
• Duration (Months): 29
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the dose-related safety and efficacy of multiple oral dosages of ELND005 as treatment for Alzheimer's disease (AD).

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: Placebo Control; Drug: ELND005; Drug: ELND005; Drug: ELND005	Phase 2

Detailed Description

ELND005 (formerly known as AZD-103), scyllo-inositol, is being investigated as an orally administered treatment for AD. ELND005 may prevent or inhibit the build up of amyloid protein in the brains of AD patients.

This is a randomized, double-blind, placebo-controlled, dose-ranging, safety and efficacy study of oral ELND005 in male and female participants aged 50-85 years with mild to moderate AD. Approximately 340 patients will be enrolled into the study at approximately 65 study sites. Patients will be randomized to receive either ELND005 or placebo. Each patient's participation will last approximately 18 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 353 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Safety and Efficacy Study of Oral ELND005 (AZD-103) in Alzheimer's Disease
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1	Drug: Placebo Control; ELND005 matched placebo capsules for oral administration, bid for 78 weeks; Other Names: scyllo-inositol
Active Comparator: 2	Drug: ELND005; ELND005 capsules for oral administration at a dose of 250 mg bid for 78 weeks; Other Names: scyllo-inositol
Active Comparator: 3	Drug: ELND005; ELND005 capsules for oral administration at a dose of 1000 mg bid for 78 weeks; Other Names: scyllo-inositol
Active Comparator: 4	Drug: ELND005; ELND005 capsules for oral administration at a dose of 2000 mg bid for 78 weeks

Outcome Measures

Primary Outcome Measures

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

   The NTB assessment is comprised of 9 instruments that measure cognition and executive function. Three of these tests measure immediate memory, next three measure delayed memory, and remaining three assess executive function. The total score is a weighted mean of the nine tests, referred to as the Z-score. Typically, scores range from -3 and 3, with lower scores suggesting greater cognitive impairment.

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

   The NTB assessment is comprised of 9 instruments that measure cognition and executive function. Three of these tests measure immediate memory, next three measure delayed memory, and remaining three assess executive function. The total score is a weighted mean of the nine tests, referred to as the Z-score. Typically, scores range from -3 and 3, with lower scores suggesting greater cognitive impairment.

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

   The ADCS-ADL is a 23-item scale that measures a subject's functional abilities as assessed by the subject's caregiver. This scale ranges from 0 to 78, with lower scores suggesting greater functional impairment.

4. 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) [Baseline and 78 weeks]

   The ADCS-ADL is a 23-item scale that measures a subject's functional abilities as assessed by the subject's caregiver. This scale ranges from 0 to 78, with lower scores suggesting greater functional impairment.

Secondary Outcome Measures

1. Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Score From Baseline to Week 78 (Full Analysis Set; FAS) [Baseline and 78 weeks]

   The ADAS-Cog primarily measures cognitive ability. The version used in this study was comprised of 12 items with scores ranging from 0 to 75. Higher scores suggest greater cognitive impairment.

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

   The CDR-SB consists of 6 items; 3 measuring cognitive ability and 3 measuring functional ability. The score for each of the six items range from 0 to 3; hence the total score is between 0 and 18. Higher scores suggest greater cognitive impairment.

3. Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS) [Baseline and 78 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of probable AD

• Age 50 to 85 years, inclusive

• Mini-Mental Status Exam (MMSE) score of 16-26, inclusive

• Brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of AD

• Fluency in English, French, or Spanish

• Stable doses of medications (cholinesterase inhibitors and memantine allowed)

• Caregiver is able to attend all study visits

Exclusion Criteria:

• Significant neurological disease other than AD

• Major psychiatric disorder

• Significant medical illness

• History of stroke or seizure

• History of a heart attack within the last 2 years

• Prior treatment with certain experimental medicines

• Presence of pacemakers or foreign metal objects in the eyes, skin, or body that would prevent patient from having MRI scan

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Alzheimer's Institute	Phoenix	Arizona	United States	85006
2	Sun Health Research Institute	Sun City	Arizona	United States	85351
3	University of Arizona, Health Sciences Center, Dept. of Neurology	Tucson	Arizona	United States	85724
4	Margolin Brain Institute	Fresno	California	United States	93720
5	Collaborative NeuroScience Network, Inc.	Garden Grove	California	United States	92845
6	UCLA Alzheimer's Disease Center, Dept. of Neurology	Los Angeles	California	United States	90095
7	UC Irvine Medical Center	Orange	California	United States	92868
8	UCSF Medical Center, Dept. of Neurology	San Francisco	California	United States	94143
9	Yale University School of Medicine, Alzheimer's Disease Research Unit	New Haven	Connecticut	United States	06510
10	Georgetown University Medical Center, Dept. of Neurology	Washington	District of Columbia	United States	20057
11	Brain Matters Research, Inc.	Delray Beach	Florida	United States	33445
12	Sunrise Clinical Research, Inc	Hollywood	Florida	United States	33021
13	Miami Jewish Home and Hospital For The Aged	Miami	Florida	United States	33137
14	Avision Research Associates, LLC	Miami	Florida	United States	33173
15	Compass Research, LLC	Orlando	Florida	United States	32806
16	Roskamp Institute	Sarasota	Florida	United States	34243
17	Neurology Clinical Research, Inc.	Sunrise	Florida	United States	33351
18	University of South Florida Suncoast Alzheimer's and Gerontology Center	Tampa	Florida	United States	33617
19	Premiere Research Institute	West Palm Beach	Florida	United States	33407
20	Emory University, Dept. of Neurology	Atlanta	Georgia	United States	30329
21	Dekalb Neurology Associates, LLC	Decatur	Georgia	United States	30033
22	Department of Neurology - Indiana University Medical Center	Indianapolis	Indiana	United States	46202
23	University of Kansas Medical Center, Department of Neurology	Kansas City	Kansas	United States	66160
24	Innovative Clinical Concepts	Paducah	Kentucky	United States	42003
25	Brigham and Women's Hospital, Dept. of Neurology	Boston	Massachusetts	United States	02115
26	University of Michigan, Taubman Health Care Center, Dept. of Neurology	Ann Arbor	Michigan	United States	48109
27	University of Nevada School of Medicine	Las Vegas	Nevada	United States	89102
28	Comprehensive Clinical Research	Berlin	New Jersey	United States	08009
29	The Memory Enhancement Center of America, Inc.	Eatontown	New Jersey	United States	07724
30	Global Medical Institutes	Princeton	New Jersey	United States	08540
31	Albuquerque Neuroscience, Inc.	Albuquerque	New Mexico	United States	87109
32	Upstate Clinical Research, LLC	Albany	New York	United States	12205
33	Neurological Associates of Albany, PC	Albany	New York	United States	12208
34	Mount Sinai Medical Center	New York	New York	United States	10029
35	Columbia University Sergievsky Center	New York	New York	United States	10032
36	AD-CARE, Monroe Community Hospital	Rochester	New York	United States	14620
37	Raleigh Neurology Associates	Raleigh	North Carolina	United States	27607
38	Neurology & Neuroscience Center of Ohio	Toledo	Ohio	United States	43623
39	Medford Neurological and Spine Clinic	Medford	Oregon	United States	97504
40	Summit Research Newtwork, Inc.	Portland	Oregon	United States	97210
41	Abington Neurological Associates, Inc.	Abington	Pennsylvania	United States	19001
42	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania	United States	19046
43	University of Pittsburgh Alzheimer Disease Research Clinic	Pittsburgh	Pennsylvania	United States	15213
44	Butler Hospital, Memory and Aging Center	Providence	Rhode Island	United States	02906
45	Alliance for Neuro Research, LLC dba Absher Neurology, PA	Greenville	South Carolina	United States	29615
46	Radiant Research San Antonio	San Antonio	Texas	United States	78229
47	University of Utah, Dept. of Neurology	Salt Lake City	Utah	United States	84108
48	Clinical Neuroscience Research Associates, Inc-The Memory Clinic	Bennington	Vermont	United States	05201
49	University of Vermont Medical Center, Fletcher Allen Health Care, Dept. of Neurology	Burlington	Vermont	United States	05405
50	University of Virginia Health System	Charlottesville	Virginia	United States	22903
51	Glenrose Rehabilitation Hospital	Edmonton	Alberta	Canada	T5G 0B7
52	University of British Columbia Hospital, Division of Neurology	Vancouver	British Columbia	Canada	V6T 2B5
53	Hotel Dieu Hospital	Kingston	Ontario	Canada	K7L 5G2
54	Saint Joseph's Health Care London, Saint Joseph's Hospital, Dept. of Cognitive Neurology	London	Ontario	Canada	N6A 4V2
55	Parkwood Hospital	London	Ontario	Canada	N6C 5J1
56	Sisters of Charity of Ottawa Health Service	Ottawa	Ontario	Canada	K1N 5C8
57	Kawartha Regional Memory Clinic	Peterborough	Ontario	Canada	K9H 2P4
58	Toronto Memory Program	Toronto	Ontario	Canada	M3B 2S7
59	Whitby Mental Health Memory Clinic	Toronto	Ontario	Canada	M5T 2S8
60	Gerontion Research, Inc.	Toronto	Ontario	Canada	M6M 3Z5
61	Neuro-Rive-Sud Memory Clinic	Greenfield Park	Quebec	Canada	J4V 2J2
62	Recherche Clinique de Neurologie (Hospital Maisonneuve Rosemont)	Montreal	Quebec	Canada	H1T 2M4

Sponsors and Collaborators

• OPKO Health, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: OPKO Health, Inc.
• ClinicalTrials.gov Identifier: NCT00568776
• Other Study ID Numbers: ELND005-AD201
• First Posted: Dec 6, 2007
• Last Update Posted: Nov 1, 2019
• Last Verified: Oct 1, 2019

• Additional relevant MeSH terms: Alzheimer Disease; Inositol

Study Results

Participant Flow

Arm/Group Title	Placebo BID	ELND005 250 mg BID	ELND005 1000 mg BID	ELND005 2000 mg BID
Arm/Group Description	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks
Period Title: Overall Study
STARTED	83	88	89	91
COMPLETED	53	52	15	19
NOT COMPLETED	30	36	74	72

Baseline Characteristics

Arm/Group Title	Placebo BID	ELND005 250 mg BID	ELND005 1000 mg BID	ELND005 2000 mg BID	Total
Arm/Group Description	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	Total of all reporting groups
Overall Participants	83	88	89	91	351
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.4 (7.83)	73.4 (7.26)	73.4 (7.56)	72.2 (8.20)	73.1 (7.7)
Sex: Female, Male (Count of Participants)
Female	47 56.6%	51 58%	48 53.9%	51 56%	197 56.1%
Male	36 43.4%	37 42%	41 46.1%	40 44%	154 43.9%
Region of Enrollment (patients) [Number]
United States	68	75	71	75	289
Canada	15	13	18	16	62

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Full Analysis Set; FAS)
Description	The NTB assessment is comprised of 9 instruments that measure cognition and executive function. Three of these tests measure immediate memory, next three measure delayed memory, and remaining three assess executive function. The total score is a weighted mean of the nine tests, referred to as the Z-score. Typically, scores range from -3 and 3, with lower scores suggesting greater cognitive impairment.
Time Frame	Baseline and 78 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo BID	ELND005 250 mg BID	ELND005 1000 mg BID	ELND005 2000 mg BID
Arm/Group Description	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks
Measure Participants	82	84	0	0
Mean (Standard Error) [Scores on a Scale]	-0.383 (0.075)	-0.350 (0.074)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, ELND005 250 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

2. Secondary Outcome

Title	Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Description	The ADAS-Cog primarily measures cognitive ability. The version used in this study was comprised of 12 items with scores ranging from 0 to 75. Higher scores suggest greater cognitive impairment.
Time Frame	Baseline and 78 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo BID	ELND005 250 mg BID	ELND005 1000 mg BID	ELND005 2000 mg BID
Arm/Group Description	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks
Measure Participants	82	84	0	0
Mean (Standard Error) [Scores on a Scale]	-8.239 (1.531)	-10.796 (1.540)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, ELND005 250 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.56
	Confidence Interval	(2-Sided) 95%; -6.33 to 1.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.90
	Estimation Comments

3. Primary Outcome

Title	Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Per Protocol Set; PPS)
Description	The NTB assessment is comprised of 9 instruments that measure cognition and executive function. Three of these tests measure immediate memory, next three measure delayed memory, and remaining three assess executive function. The total score is a weighted mean of the nine tests, referred to as the Z-score. Typically, scores range from -3 and 3, with lower scores suggesting greater cognitive impairment.
Time Frame	Baseline and 78 weeks

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS): all randomized patients who received at least one dose of ELND005 250 mg or placebo, completed all scheduled visits up to Week 78, were at least 80% compliant with study drug, and met all inclusion/exclusion criteria.

Arm/Group Title	Placebo BID	ELND005 250 mg BID	ELND005 1000 mg BID	ELND005 2000 mg BID
Arm/Group Description	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks
Measure Participants	47	49	0	0
Mean (Standard Error) [Scores on a Scale]	-0.369 (0.093)	-0.222 (0.095)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, ELND005 250 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

4. Primary Outcome

Title	Change From Baseline to Week 78 in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score (Full Analysis Set; FAS)
Description	The ADCS-ADL is a 23-item scale that measures a subject's functional abilities as assessed by the subject's caregiver. This scale ranges from 0 to 78, with lower scores suggesting greater functional impairment.
Time Frame	Baseline and 78 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo BID	ELND005 250 mg BID	ELND005 1000 mg BID	ELND005 2000 mg BID
Arm/Group Description	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks
Measure Participants	82	84	0	0
Mean (Standard Error) [Scores on a Scale]	-9.467 (1.641)	-10.861 (1.604)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, ELND005 250 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.39
	Confidence Interval	(2-Sided) 95%; -5.41 to 2.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.03
	Estimation Comments

5. Primary Outcome

Title	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)
Description	The ADCS-ADL is a 23-item scale that measures a subject's functional abilities as assessed by the subject's caregiver. This scale ranges from 0 to 78, with lower scores suggesting greater functional impairment.
Time Frame	Baseline and 78 weeks

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS): all randomized patients who received at least one dose of ELND005 250 mg or placebo, completed all scheduled visits up to Week 78, were at least 80% compliant with study drug, and met all inclusion/exclusion criteria.

Arm/Group Title	Placebo BID	ELND005 250 mg BID	ELND005 1000 mg BID	ELND005 2000 mg BID
Arm/Group Description	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks
Measure Participants	47	49	0	0
Mean (Standard Error) [Scores on a Scale]	-9.635 (1.779)	-8.987 (1.760)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, ELND005 250 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; -3.73 to 5.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.20
	Estimation Comments

6. Secondary Outcome

Title	Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Description	The CDR-SB consists of 6 items; 3 measuring cognitive ability and 3 measuring functional ability. The score for each of the six items range from 0 to 3; hence the total score is between 0 and 18. Higher scores suggest greater cognitive impairment.
Time Frame	Baseline and 78 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo BID	ELND005 250 mg BID	ELND005 1000 mg BID	ELND005 2000 mg BID
Arm/Group Description	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks
Measure Participants	82	84	0	0
Mean (Standard Error) [Scores on a Scale]	-2.742 (0.363)	-2.452 (0.357)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, ELND005 250 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95%; -0.63 to 1.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.47
	Estimation Comments

7. Secondary Outcome

Title	Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS)
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo BID	ELND005 250 mg BID	ELND005 1000 mg BID	ELND005 2000 mg BID
Arm/Group Description	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks	oral administration for 78 weeks
Measure Participants	82	84	0	0
Mean (Standard Error) [Scores on a Scale]	-6.132 (1.851)	-5.116 (1.814)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo BID, ELND005 250 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; -3.43 to 5.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.24
	Estimation Comments

Adverse Events

Time Frame	Reported adverse events include events starting at or after Screening to Week 84
Adverse Event Reporting 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.
Arm/Group Title	Placebo BID		ELND005 250 mg BID		ELND005 1000 mg BID		ELND005 2000 mg BID
Arm/Group Description	oral administration for 78 weeks		oral administration for 78 weeks		oral administration for 78 weeks		oral administration for 78 weeks
All Cause Mortality
	Placebo BID		ELND005 250 mg BID		ELND005 1000 mg BID		ELND005 2000 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo BID		ELND005 250 mg BID		ELND005 1000 mg BID		ELND005 2000 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/83 (13.3%)		19/88 (21.6%)		20/89 (22.5%)		21/91 (23.1%)
Blood and lymphatic system disorders
Haemorrhagic Anaemia	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Cardiac disorders
Angina Unstable	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Atrial Fribrillation	1/83 (1.2%)		1/88 (1.1%)		1/89 (1.1%)		1/91 (1.1%)
Atrial Futter	1/83 (1.2%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Cardiac Arrest	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Cardiac Failure Congestive	0/83 (0%)		0/88 (0%)		0/89 (0%)		2/91 (2.2%)
Coronary Artery Occlusion	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Myocardial Infarction	1/83 (1.2%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Supraventricular Tachycardia	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Eye disorders
Glaucoma	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Retinal Vein Occlusion	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Vitreous Haemorrhage	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Gastrointestinal disorders
Gastric Ulcer Haemorrhage	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Gastritis	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Gastritis Hemorrhagic	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Hemorrhoidal hemorrhage	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Pancreatitis	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Small Intestinal Obstruction	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
General disorders
Hypothermia	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Sudden Death	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		1/91 (1.1%)
Hepatobiliary disorders
Cholecystitis	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Infections and infestations
Arthritis Bacterial	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Bacterial Sepsis	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Kidney Infection	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Pneumonia	0/83 (0%)		0/88 (0%)		2/89 (2.2%)		3/91 (3.3%)
Pneumonia Bacterial	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Staphylococcal Infection	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Urinary Tract Infection	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		3/91 (3.3%)
Urosepsis	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Viral Infection	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Injury, poisoning and procedural complications
Accidental Overdose	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Compression Fracture	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Contusion	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Fall	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		1/91 (1.1%)
Hip Fracture	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Jaw Fracture	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Laceration	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Multiple Fractures	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Post Procedural Haematoma	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Postoperative Ileus	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Subdural Hematoma	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Investigations
Electrocardiogram Change	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Hepatic Enzyme Increased	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Lipase Increased	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Metabolism and nutrition disorders
Dehydration	2/83 (2.4%)		1/88 (1.1%)		2/89 (2.2%)		2/91 (2.2%)
Failure to Thrive	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Hyperglycemia	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Musculoskeletal and connective tissue disorders
Mobility Decreased	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Breast Cancer	0/83 (0%)		3/88 (3.4%)		0/89 (0%)		0/91 (0%)
Breast Cancer In Situ	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Colon Cancer	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Colorectal Cancer	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Renal Cell Carcinoma	0/83 (0%)		0/88 (0%)		0/89 (0%)		2/91 (2.2%)
Squamous Cell Carcinoma	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Squamous Cell Carcinoma of Skin	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Nervous system disorders
Carotid Artery Occlusion	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Cerebral Hemorrhage	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Cerebrovascular Accident	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		1/91 (1.1%)
Dementia Alzheimer's Type	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Dizziness	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Encephalopathy	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Haemorrhagic Stroke	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Ischaemic Cerebral Infarction	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Syncope	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		1/91 (1.1%)
Transient Ischaemic Attack	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Psychiatric disorders
Acute Psychosis	0/83 (0%)		0/88 (0%)		0/89 (0%)		1/91 (1.1%)
Agitation	0/83 (0%)		1/88 (1.1%)		1/89 (1.1%)		0/91 (0%)
Confusional State	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Delirium	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Mental Status Changes	1/83 (1.2%)		0/88 (0%)		0/89 (0%)		0/91 (0%)
Psychotic Disorder	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		1/91 (1.1%)
Renal and urinary disorders
Renal Failure Acute	0/83 (0%)		0/88 (0%)		2/89 (2.2%)		0/91 (0%)
Urinary Retention	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		0/91 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/83 (0%)		0/88 (0%)		2/89 (2.2%)		0/91 (0%)
Pneumonia Aspiration	0/83 (0%)		0/88 (0%)		2/89 (2.2%)		0/91 (0%)
Pneumothorax	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Pulmonary Embolism	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		1/91 (1.1%)
Respiratory Failure	0/83 (0%)		0/88 (0%)		1/89 (1.1%)		1/91 (1.1%)
Vascular disorders
Aortic Thrombosis	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Deep Vein Thrombosis	0/83 (0%)		1/88 (1.1%)		0/89 (0%)		0/91 (0%)
Other (Not Including Serious) Adverse Events
	Placebo BID		ELND005 250 mg BID		ELND005 1000 mg BID		ELND005 2000 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/83 (57.8%)		46/88 (52.3%)		45/89 (50.6%)		57/91 (62.6%)
Gastrointestinal disorders
Diarrhoea	6/83 (7.2%)		9/88 (10.2%)		8/89 (9%)		12/91 (13.2%)
Nausea	4/83 (4.8%)		8/88 (9.1%)		3/89 (3.4%)		14/91 (15.4%)
Vomiting	3/83 (3.6%)		5/88 (5.7%)		3/89 (3.4%)		8/91 (8.8%)
General disorders
Fatigue	4/83 (4.8%)		6/88 (6.8%)		6/89 (6.7%)		7/91 (7.7%)
Infections and infestations
Urinary Tract Infection	7/83 (8.4%)		12/88 (13.6%)		4/89 (4.5%)		11/91 (12.1%)
Upper Respiratory Tract Infection	5/83 (6%)		9/88 (10.2%)		3/89 (3.4%)		3/91 (3.3%)
Injury, poisoning and procedural complications
Fall	5/83 (6%)		11/88 (12.5%)		10/89 (11.2%)		14/91 (15.4%)
Nervous system disorders
Dizziness	7/83 (8.4%)		4/88 (4.5%)		6/89 (6.7%)		11/91 (12.1%)
Headache	12/83 (14.5%)		4/88 (4.5%)		11/89 (12.4%)		8/91 (8.8%)
Psychiatric disorders
Agitation	5/83 (6%)		4/88 (4.5%)		9/89 (10.1%)		6/91 (6.6%)
Confusional State	3/83 (3.6%)		7/88 (8%)		4/89 (4.5%)		4/91 (4.4%)
Depression	4/83 (4.8%)		10/88 (11.4%)		4/89 (4.5%)		12/91 (13.2%)
Insomnia	5/83 (6%)		3/88 (3.4%)		2/89 (2.2%)		8/91 (8.8%)

Limitations/Caveats

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

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator may publish after release of multi-center study publication, or 18 months after database lock of overall study. Sponsor has 60 days to review any proposed publication and request removal of Sponsor's confidential information. Sponsor may request an additional 90 days if filing a patent.