Study Evaluating the Safety and Efficacy of Bapineuzumab in Alzheimer Disease Patients

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00676143
• Collaborator: (none)
• Enrollment: 1,100
• Locations: 287
• Arms: 2
• Duration (Months): 58
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a study to evaluate the efficacy and safety of multiple doses of bapineuzumab in patients with mild to moderate Alzheimer Disease. Patients will receive either bapineuzumab or placebo. Each patient's participation will last approximately 1.5 years.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: bapineuzumab; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase Iii, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Efficacy And Safety Trial Of Bapineuzumab (Aab 001, Eln115727) In Subjects With Mild To Moderate Alzheimer Disease Who Are Apolipoprotein E 4 Carriers
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bapineuzumab 0.5 mg/kg	Drug: bapineuzumab; Bapineuzumab 0.5 mg/kg administered by IV infusion approximately every 13 weeks through week 65.; Other Names: AAB-001
Placebo Comparator: Placebo	Drug: placebo; Placebo will be administered by IV infusion approximately every 13 weeks through week 65.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog)/11 Subscale Total Score at Week 78 [Baseline and 78 weeks]

   The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4) constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8) remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension. This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.

2. Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 78 [Baseline and 78 weeks]

   The DAD measures instrumental and basic activities of daily living in participants with Alzheimer's Disease (AD). The DAD is administered to the participants'caregiver in the form of an interview. This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced by the participant. This scale assesses a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. A total score is obtained by adding the rating for each question and converting this total score out of 100. Higher scores indicate better function; a positive change from baseline indicates an improvement.

Secondary Outcome Measures

1. Change From Baseline in Brain Amyloid Burden at Week 71 [Baseline and 71 weeks]

   Brain amyloid burden as imaged by 11C-Pittsburgh compound B (PIB) positron emission tomography (PET). The latter is a semi-quantitative measure of the extent of fibrillar amyloid in the brain. PIB PET measurements were made in cortical regions found to have the highest burden of fibrillar amyloid at autopsy in participants diagnosed as having Alzheimer's pathology, and also regions reported to have the highest average retention of PIB signal in previous PET studies enrolling participants with probable AD. This parameter reflects overall brain amyloid deposition as indexed by imaging. The change from baseline was measured as average standard uptake value ratio (SUVr) in prespecified regions of interest (ROI) assessed by PIB PET imaging in a subset of participants.

2. Change From Baseline in Cerebrospinal Fluid (CSF) Phospho-tau Levels at Week 71 [Baseline and 71 Weeks]

   Biomarkers CSF phospho-tau is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD. Accordingly, a reduction from baseline in levels of CSF tau in participants who received bapineuzumab compared with participants who received placebo may be indicative of a reduction in neuronal loss in participants treated with bapineuzumab.

3. Change From Baseline in Brain Volume, as Assessed by Magnetic Resonance Imaging Brain Boundary Shift Integral (MRI BBSI), at Week 71 [Baseline and 71 Weeks]

   Cerebral atrophy correlates closely with the gradual cognitive decline in AD and can be visualized by MRI. The BBSI technique involves positional matching of serial 3-dimensional MRI brain images, such that brain MRI-image volumes were first registered and then subtracted from each other. Atrophy rates would generally be expected to be lower if the underlying disease was attenuated by effective treatment.

4. Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78 [Week 39 to Week 78]

   Treatment differences are estimated using least-squares (LS) means with factor levels weighted according to overall analysis population proportions. ADAS-Cog/11 total score range is 0 (least impairment) to 70 (most impairment); a negative treatment difference (bapineuzumab minus placebo) favors bapineuzumab. Within the MMRMs for ADAS-Cog/11 described for the primary analyses, linear contrasts were formed to test increasing trend of the differences between bapineuzumab and placebo from Week 39 (the 9-month visit) through Week 78 (the 18 -month visit) for each variable, which is equivalent to testing a positive slope of the differences between each bapineuzumab dose group and placebo from Week 39 through Week 78. Results are from a restricted maximum likelihood (REML)-based mixed model for MMRM.

5. Divergence of Effect on the DAD Total Scores From Week 39 to Week 78 [Week 39 to Week 78]

   Treatment differences are estimated using least-squares (LS) means with factor levels weighted according to overall analysis population proportions. DAD total score range is 0 to 100; a positive treatment difference (bapineuzumab minus placebo) favors bapineuzumab. Within the MMRMs for ADAS-Cog/11 described for the primary analyses, linear contrasts were formed to test increasing trend of the differences between bapineuzumab and placebo from Week 39 (the 9-month visit) through Week 78 (the 18 -month visit) for each variable, which is equivalent to testing a positive slope of the differences between each bapineuzumab dose group and placebo from Week 39 through Week 78. Results are from a restricted maximum likelihood (REML)-based mixed model for MMRM.

6. Time to First Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan) [Baseline and 78 Weeks]

   The time to first median placebo deterioration, defined as the first time a participant experienced an increase (worsening) from baseline in ADAS-Cog/11 total score greater than or equal to the median worsening observed at Week 78 in the placebo group. The Kaplan Meier estimate of median time to first median placebo deterioration was presented.

7. Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan) [Baseline and 78 Weeks]

   The time to first clinically meaningful deterioration was defined as the first time a participant experienced an increase (worsening) from baseline in ADAS-Cog/11 total score of >=7.

8. Time to First Median Placebo Deterioration on DAD Total Score (EU Analysis Plan) [Baseline and 78 Weeks]

   The time to first median placebo deterioration was defined as the first time a participant experienced a decrease (worsening) in DAD total score greater than or equal to the median worsening at Week 78 in the placebo group.

9. Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis) [Baseline and 78 Weeks]

   The time to first clinically meaningful deterioration was defined as the first time a participant experienced a decrease (worsening) from baseline in DAD total score of >=12.

10. Change From Baseline in Dependence Scale Total Score at Week 78 [Baseline and 78 Weeks]

    The Dependence Scale (DS) is a 13-item, caregiver-rated instrument for determining the amount of support required by a participant with AD. The DS total score ranges from 0 to 15, with higher scores indicating more need for assistance. The DS was administered as an interview to the caregiver at scheduled study visits.

11. Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (EU Analysis Plan) [Baseline and 78 Weeks]

    Percentage of participants with worsening from baseline to Week 78 in ADAS-Cog/11 total score of ≤0, ≤3, and ≤7 points were reported. In order to calculate time to first median placebo deterioration in ADAS-Cog/11, the median change from baseline to Week 78 among the placebo participants of the mITT analysis population were determined. The median changes were used as the cutpoints for determining "deterioration" for Alzheimer's disease participants in the study. If the median change from baseline to Week 78 in the ADAS-Cog/11 total score among the placebo participants of the mITT Analysis Population is 7 points, then the first median placebo deterioration is the first time where there is a worsening on the ADAS-Cog/11 total score of 7 points or more and the worsening is confirmed by the ADAS-Cog/11 assessment at the next non-missing visit.

12. Percentage of Responders for ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan) [Baseline and 78 Weeks]

    Percentage of participants whose increase (worsening) from baseline to Week 78 in ADAS-Cog/11 total score was <7.

13. Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (EU Analysis Plan) [Baseline and 78 Weeks]

    Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score of ≤ 0, ≤ 6, and ≤ 12 points. In order to calculate time to first median placebo deterioration in DAD, the median change from baseline to Week 78 among the placebo participants of the mITT analysis population were determined. The median changes were used as the cutpoints for determining "deterioration" for Alzheimer's disease participants in the study. If the median change from baseline to Week 78 in the DAD total score among the placebo participants of the mITT Analysis Population is 7 points, then the first median placebo deterioration is the first time where there is a worsening on the DAD total score of 7 points or more and the worsening is confirmed by the DAD assessment at the next non-missing visit.

14. Percentage of Responders for DAD Total Score at Week 78 (US Analysis Plan) [Baseline and 78 Weeks]

    Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score was <12.

15. Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78 [Baseline and 78 Weeks]

    The CDR-SOB is a global clinical staging instrument that sums 6 clinical ratings: 1) memory, 2) orientation, 3) judgment and problem solving, 4) involvement in community affairs, 5) home and hobbies, and 6) personal care based on the Clinical Dementia Rating Scale (CDR) interview. The CDR includes discussions with the participant and caregiver using a structured format. This scale had to be administered by a trained and certified global rater who did not have access to any information regarding adverse events experienced by the participant. CDR-SOB total score range is 0 (least impairment) to 18 (most impairment); a negative change from baseline indicates an improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 88 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of probable AD, with MMSE score of 16-26, and brain MRI consistent with the diagnosis of AD

• Concurrent use of cholinesterase inhibitor or memantine allowed, if stable.

• Caregiver will participate and be able to attend clinic visits with patient.

Exclusion Criteria:

• Significant neurological disease other than AD, or a major psychiatric disorder

• Contraindication to undergo brain MRI (e.g., pacemaker, CSF shunt, or foreign metal objects in the body)

• Woman of childbearing potential

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Psychiatric Medicine	Birmingham	Alabama	United States	35294
2	Participant and Clinical Interactions Resources	Birmingham	Alabama	United States	35294
3	UAB Clinical Research Pharmacy-Russell Clinic	Birmingham	Alabama	United States	35294
4	University of Alabama-Birmingham	Birmingham	Alabama	United States	35294
5	Dedicated Clinical Research	Goodyear	Arizona	United States	85395
6	Banner Alzheimer's Institute	Phoenix	Arizona	United States	85006
7	Jeffrey S. Gitt, DO, PC	Phoenix	Arizona	United States	85032
8	The Compounding Center	Phoenix	Arizona	United States	85032
9	HOPE Research Institute	Phoenix	Arizona	United States	85050
10	Clinical Trials, Inc.	Little Rock	Arkansas	United States	72205
11	AC Institute, Incorporated	Carson	California	United States	90746
12	Collaborative Neuroscience Network, Inc	Long Beach	California	United States	90806
13	San Francisco Clinical Research Center	San Francisco	California	United States	94109
14	Alpine Clinical Research Center, Inc.	Boulder	Colorado	United States	80304
15	Associated Neurologists, PC	Boulder	Colorado	United States	80304
16	Mile HIgh Research Center	Denver	Colorado	United States	80218
17	Associated Neurologists of Southern Connecticut, P.C.	Fairfield	Connecticut	United States	06824
18	Bendheim Cancer Center	Greenwich	Connecticut	United States	06830
19	Center for Healthy Aging	Greenwich	Connecticut	United States	06830
20	Alzheimer's Disease Research Unit	New Haven	Connecticut	United States	06510
21	Hospital Research Unit	New Haven	Connecticut	United States	06510
22	Investigational Drug Service	New Haven	Connecticut	United States	06511
23	Moshe Hasbani, MD	New Haven	Connecticut	United States	06511
24	Norman S. Werdiger, MD	New Haven	Connecticut	United States	06519
25	MR Research Center	New Haven	Connecticut	United States	06520
26	Yale PET Center	New Haven	Connecticut	United States	06520
27	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut	United States	06851
28	JEM Research Institute, LLC	Atlantis	Florida	United States	33462
29	JEM Research Institute	Atlantis	Florida	United States	33462
30	Medical Specialist of the Palm Beaches	Atlantis	Florida	United States	33462
31	Brain Matters Research	Delray Beach	Florida	United States	33445
32	Compass Research, LLC	Orlando	Florida	United States	32806
33	Palm Beach Neurological Center	Palm Beach Gardens	Florida	United States	33418
34	Neurostudies Inc	Port Charlotte	Florida	United States	33952
35	Roskamp Institute	Sarasota	Florida	United States	34243
36	University of South Florida	Tampa	Florida	United States	33613
37	Dekalb Neurology Associates, LLC/NeuroStudies.net, LLC	Decatur	Georgia	United States	30033
38	Neurostudies.net	Decatur	Georgia	United States	30033
39	NeuroStudies.net	Lawrenceville	Georgia	United States	30045
40	Alexian Brothers Medical Center	Elk Grove Village	Illinois	United States	60007
41	Southern Illinois University School of Medicine Department	Springfield	Illinois	United States	62702
42	Memorial Medical Center	Springfield	Illinois	United States	62781
43	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
44	Lake Charles Clinical Trials	Lake Charles	Louisiana	United States	70629
45	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
46	Massachusetts General Hosptial	Boston	Massachusetts	United States	02114
47	Brigham & Womens Hospital	Boston	Massachusetts	United States	02115
48	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
49	Boston Univeristy ADCRP	Boston	Massachusetts	United States	02118
50	General Clincial Research Center (Infusion Location)	Boston	Massachusetts	United States	02118
51	IDS Pharmacy (Drug Receipt). Attn:Hyesson Hong	Boston	Massachusetts	United States	02118
52	Shields MRI	Dartmouth	Massachusetts	United States	02747
53	Neuroscience Research of the Berkshires	Pittsfield	Massachusetts	United States	01201
54	Springfield Neurology Associates, LLC	Springfield	Massachusetts	United States	01104
55	University of Michigan Health System	Ann Arbor,	Michigan	United States	48109-5872
56	University of Michigan Hospital and Health System	Ann Arbor	Michigan	United States	48105-2945
57	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
58	University of Michigan Health System	Ann Arbor	Michigan	United States	48110
59	Michigan State University	East Lansing	Michigan	United States	48824
60	Hattiesburg Clinic	Hattiesburg	Mississippi	United States	39401
61	The Center for Pharmaceutical Research P.C.	Kansas City	Missouri	United States	64114
62	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey	United States	07724
63	Pharmcare USA	Edison	New Jersey	United States	08837
64	Alzheimer's Research Corp./Merician Institute for Aging	Manchester	New Jersey	United States	08759
65	Neurological Care of Central New York	Liverpool	New York	United States	13088
66	Carolina Neuropsychological Services, Inc	Raleigh	North Carolina	United States	27607
67	Healthsouth Blue Ridge Surgery Center	Raleigh	North Carolina	United States	27607
68	Raleigh Neurology Associates	Raleigh	North Carolina	United States	27607
69	Wake Radiology Associates	Raleigh	North Carolina	United States	27607
70	Ohio State University Imaging@Martha Moorehouse	Columbs	Ohio	United States	43210
71	The Ohio State University	Columbs	Ohio	United States	43210
72	The Ohio State University	Columbus	Ohio	United States	43210
73	Summit Research Network(Oregon) Inc.	Portland	Oregon	United States	97210
74	Providence Brain Institute	Portland	Oregon	United States	97225
75	Providence Cognitive Assessment Clinic	Portland	Oregon	United States	97225
76	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
77	Dr. Michael Gabe (Clinic)	Silverton	Oregon	United States	97381
78	Abington Memorial Hosptial	Abington	Pennsylvania	United States	19001
79	Abington Neurological Associates	Abington	Pennsylvania	United States	19001
80	Abington Neurological Assoc	Abington	Pennsylvania	United States	19001
81	Andorra MRI of Flourtown	Flourtown	Pennsylvania	United States	19031
82	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania	United States	19046
83	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
84	Investigational New Drug Services	Philadelphia	Pennsylvania	United States	19104
85	University of Pennsylvania-Penn Memory Center	Philadelphia	Pennsylvania	United States	19104
86	UPENN Clinical and Transitional Research Center	Philadelphia	Pennsylvania	United States	19104
87	Jefferson Hospital for Neuroscience	Philadelphia	Pennsylvania	United States	19107
88	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
89	Abington Neurological Associates	Willow Grove	Pennsylvania	United States	19090
90	Rhode Island Mood and Memory Research Institute	East Providence	Rhode Island	United States	02914
91	Simpson's Pharmacy	Pawtucket	Rhode Island	United States	02861
92	Butler Hospital	Providence	Rhode Island	United States	02906
93	Medical University of South Carolina Hospitals and Clinics	Charleston	South Carolina	United States	29425
94	Medical University of South Carolina	Charleston	South Carolina	United States	29425
95	MUSC	Charleston	South Carolina	United States	29425
96	Medical University of South Carolina	North Charleston	South Carolina	United States	29406
97	Texas Neurology, P.A.	Dallas	Texas	United States	75214
98	Innovative Clinical Trials	San Antonio	Texas	United States	78229
99	Integra Clinical Research	San Antonio	Texas	United States	78229
100	Integra Clinical Research, LLC	San Antonio	Texas	United States	78231
101	Integra Clinical Research	San Antonio	Texas	United States	78231
102	Vista Infusions	San Antonio	Texas	United States	78231
103	Inventive Infusion Solutions	San Antonio	Texas	United States	78258
104	Inventive Infusions Solutions	San Antonio	Texas	United States	78258
105	The Memory Clinic	Bennington	Vermont	United States	05201
106	The Pharmacy	Bennington	Vermont	United States	05201
107	Waisman Center (PET only)	Madison	Wisconsin	United States	53705-2280
108	University of Wisconsin School of Medicine and Public Health	Madison	Wisconsin	United States	53705
109	Wm S. Middleton Memorial Veterans Hospital	Madison	Wisconsin	United States	53705
110	University of Wisconsin Hospitals and Clinics	Madison	Wisconsin	United States	53792
111	University of Wisconsin School of Medicine and Public Health	Madison	Wisconsin	United States	53792
112	Instituto Medico Congreso	Buenos Aires		Argentina	1090
113	Cemic University Hospital	Buenos Aires		Argentina	1431
114	Hospital Italiano de Buenos Aires	Buenos Aires		Argentina	C1199ABD
115	Instituto Kremer	Cordoba		Argentina	5004
116	Gosford Hospital; Pharmacy Dept	Gosford	New South Wales	Australia	2250
117	Gosford Hospital	Gosford	New South Wales	Australia	2250
118	Hornsby Kuringai Hospital	Hornsby	New South Wales	Australia	2077
119	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
120	The Queen Elizabeth Hospital	Woodville South	South Australia	Australia	5011
121	CDAMS Ballarat Base Hospital	Ballarat	Victoria	Australia	3353
122	Heidelberg Repatriation Hospital	West Heidelberg	Victoria	Australia	3081
123	Hollywood Hospital; Pharmacy Dept	Nedlands	Western Australia	Australia	6009
124	McCusker Alzheimer's Research Foundation, Inc.	Nedlands	Western Australia	Australia	6009
125	Medizinische Universitaet Graz	Graz		Austria	8036
126	Landeskrankenhaus Klagenfurt	Klagenfurt		Austria	A-9020
127	Allg. Krankenhaus der Stadt Wien	Wien		Austria	1090
128	SZ Sued - Kaiser-Franz-Josef-Spital	Wien		Austria	1220
129	Donauspital	Wien		Austria	A-1220
130	ZNA Middelheim	Antwerpen		Belgium	2020
131	Az. St. Jan Ruddershove 35	Brugge		Belgium	8000
132	Cliniques Universitaires St Luc	Brussels		Belgium	1200
133	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	2650
134	Universitair Ziekenhuis Gasthuisberg	Leuven		Belgium	3000
135	H.-Hartziekenhuis Roeselare-Menen	Roeselare		Belgium	8800
136	Psicomedica Research Group	Santiago		Chile	7530193
137	Especialidades Medicas LyS	Santiago		Chile
138	University Hospital Center Zagreb	Zagreb		Croatia	10000
139	Ita-Suomen Yliopisto	Kuopio		Finland	FIN-70210
140	University of Turku / CRST	Turku		Finland	20520
141	CHU Pellegrin	Bordeaux Cedex		France	33076
142	Hopital neurologique du Pr A. Vighetto	Bron		France	69677
143	Centre d'Imagerie medicale de Basse Normandie	Caen		France	14000
144	CHU de Caen	Caen		France	14033
145	Hôpitaux Civils de Colmar	Colmar		France	68024
146	CHU de Dijon	Dijon		France	21033
147	CHRU de Lille	Lille		France	59037
148	Hôpital la Timone	Marseille		France	13385
149	CHU Hôpital Gui de Chaulliac	Montpellier		France	34295
150	CHU Nord - Hôpital Guillaume et René Laënnec	Nantes - Saint Herblain		France	44093
151	Hôpital Cimiez C.M.R.R.	Nice		France	06000
152	Service d'Imagerie Medicale	Nice		France	06002
153	Groupe Hospitalier Broca-La Rochefoucauld	Paris		France	75013
154	Hôpital Pitié-Salpétrière	Paris		France	75651
155	Hospital Jean Bernard CIC	Poitiers		France	86000
156	C.H.U de Reims	Reims		France	51092
157	CHU de Rennes	Rennes Cedex		France	35064
158	CHU - Hopital Charles Nicolle	Rouen		France	76031
159	Hôpital Purpan	Toulouse		France	31059
160	CHU Toulouse - Site Casselardit	Toulouse		France	31300
161	Charite-Universitätsmedizin Berlin	Berlin		Germany	14050
162	St. Josef-Klinikum	Bochum		Germany	44791
163	Universitaetsklinikum Dresden	Dresden		Germany	01307
164	Klinikum der Albert-Ludwigs-Universitaet Freiburg	Freiburg		Germany	79106
165	Ortenau Klinikum Offenburg	Offenburg		Germany	77654
166	Universitaetsklinikum Ulm	Ulm		Germany	89081
167	A.O. Umberto I	Ancona		Italy	60020
168	Sezione di Neurologia - Dipartimento di Neuroscienze	Ancona		Italy	60020
169	Clinica Neurologica - II Neurologia	Brescia		Italy	25123
170	Dipartimento di Neuroscienze,	Catania		Italy	95123
171	Unita' Operativa Complessa di Neurologia	Catania		Italy	95126
172	CeSI (Centro di Scienze dell'invecchiamento) -	Chieti		Italy	66013
173	Fondazione IRCCS- Istituto Neurologico Carlo Besta	Milano		Italy	20133
174	Ospedale S. Gerardo	Monza		Italy	20052
175	Clinica Neurologica	Roma		Italy	00128
176	Unita' Operativa C - Riabilitazione Neurologica	Roma		Italy	00179
177	Universita degli Studi di Siena	Siena		Italy	53100
178	Nagoya City University Hospital	Nagoya	Aichi,	Japan	467-8602
179	National Hospital Organization Tokyo National Hospital	Kiyose	Tokyo	Japan	204-8585
180	Yachiyo Hospital	Aichi		Japan	446-8510
181	Kashiwado Hospital	Chiba		Japan	260-8656
182	National Hospital Organization Chiba-East Hospital	Chiba		Japan	260-8712
183	Nippon Medical School Chiba Hokusoh Hospital	Chiba		Japan	270-1694
184	National Hospital Organization Kokura Medical Center	Fukuoka		Japan	802-8533
185	Maebashi Red Cross Hospital	Gunma		Japan	371-0014
186	Gunma University Hospital	Gunma		Japan	371-8511
187	Shinozuka Hospital	Gunma		Japan	375-0017
188	National Hospital Organization Hiroshima-nishi Medical Ctr.	Hiroshima		Japan	739-0696
189	Kobe University Hospital	Hyogo		Japan	650-0017
190	Nishi-Kobe Medical Center	Hyogo		Japan	651-2273
191	Kobe City Hospital Org Kobe City Medical Cente West Hp	Hyogo		Japan	653-0013
192	Iwate Medical University Hospital	Iwate		Japan	020-8505
193	Kagawa University Hospital	Kagawa		Japan	761-0793
194	Nippon Medical School Musashi Kosugi Hospital	Kanagawa		Japan	211-8533
195	Yokohama City University Medical Center	Kanagawa		Japan	232-0024
196	Shonan Atsugi Hospital	Kanagawa		Japan	243-8551
197	Rakuwakai Otowa Hospital	Kyoto		Japan	607-8062
198	National Hospital Organization Minami-Kyoto Hospital	Kyoto		Japan	610-0113
199	National Hospital Organization Maizuru Medical Center	Kyoto		Japan	625-8502
200	National Hospital Organization Matsumoto Medical Center	Nagano		Japan	399-0021
201	National Hospital Organization Niigata National Hospital	Niigata		Japan	945-8585
202	Okayama University Hospital	Okayama		Japan	700-8558
203	National Hospital Organization Minami-Okayama Medical Center	Okayama		Japan	701-0304
204	Osaka City University Hospital	Osaka		Japan	545-8586
205	Osaka University Hospital	Osaka		Japan	565-0871
206	Kansai Medical University Takii Hospital	Osaka		Japan	570-8507
207	National HP.Org.Shizuoka Inst.Epilepsy,Neurological Disorder	Shizuoka		Japan	420-8688
208	Juntendo University Hospital	Tokyo		Japan	113-8431
209	Juntendo Tokyo Koto Geriatric Medical Center	Tokyo		Japan	136-0075
210	Tokyo Metropolitan Health and Med. Treatment Co. Ebara Hosp	Tokyo		Japan	145-0065
211	Tokyo Medical University Hospital	Tokyo		Japan	160-0023
212	Tokyo Medical University Hachioji Medical Center	Tokyo		Japan	193-0998
213	OCA Hospital	Monterrey	Nuevo León	Mexico	64000
214	Instituto Biomedico de Investigacion A.C	Aguascalientes		Mexico	20127
215	Amphia Ziekenhuis	Breda	Noord Brabant	Netherlands	4818 CK
216	Tergooi Ziekenhuizen	Hilversum	Noord Holland	Netherlands	1213 XZ
217	Kennemer Gasthuis	Haarlem	The Netherlands	Netherlands	2035 RC
218	Jeroen Bosch Ziekenhuis	's-Hertogenbosch		Netherlands	5223 GZ
219	Medisch Centrum Alkmaar	Alkmaar		Netherlands	1815 JD
220	Vrije Universiteit Medisch Centrum	Amsterdam		Netherlands	1081 HV
221	Catharina Ziekenhuis	Eindhoven		Netherlands	5623 EJ
222	Medisch Centrum Leeuwarden	Leeuwarden		Netherlands	8934 AD
223	Erasmus MC	Rotterdam		Netherlands	3015 CE
224	The Memory Clinic	Auckland	NZ	New Zealand	0622
225	Signet Research	Christchurch		New Zealand	8014
226	NZOZ Dom Suer Ryder, Pallmed Sp. z o.o.	Bydgoszcz		Poland	85-796
227	Szpital Uniwersytecki, Oddzial Kliniczny Klinik Chorob Wewnetrznych i	Krakow		Poland	31-531
228	NZOZ "NEURO-KARD" "ILKOWSKI I PARTNERZY" Spolka Partnerska Lekarzy	Poznan		Poland	61-289
229	Oddzial Neurologiczny i Udarowy Szpital Wolski im. dr Anny Gostynskiej,	Warszawa		Poland	01-211
230	Samodzielny Publiczny Centralny Szpital Kliniczny, Katedra i Klinika	Warszawa		Poland	02-097
231	Hospital Fernando da Fonseca	Amadora		Portugal	2720-276
232	Hospitais Da Universidade De Coimbra	Coimbra		Portugal	3000-075
233	Hospital Santa Maria	Lisboa		Portugal	1649-028
234	Klinicki centar Srbije	Belgrade		Serbia	11000
235	Clinical Centre Kragujevac, Clinic of Psichiatry	Kragujevac		Serbia	34000
236	Klinicki Centar Vojvodina	Novi Sad		Serbia	21000
237	Diagnostic Imaging Center	Sremska Kamenica		Serbia	21204
238	Institute for Cardiovascular Diseases of Vojvodina	Sremska Kamenica		Serbia	21204
239	Psychiatricka ambulancia	Bratislava		Slovakia	820 07
240	Univerzitna nemocnica Bratislava	Bratislava		Slovakia	825 56
241	Psychiatricka nemocnica Michalovce, n.o.	Michalovce		Slovakia	071 01
242	Vseobecna nemocnica Rimavska Sobota	Rimavska Sobota		Slovakia	979 12
243	Boithuso Caregivers	Johannesburg	Gauteng	South Africa	1709
244	The Osteoporosis and Memory Centre	Johannesburg	Gauteng	South Africa	2196
245	Denmar Clinic	Pretoria	Gauteng	South Africa	0081
246	St Augustine's Medical Centre 2	Durban	Kwa Zulu Natal	South Africa	4001
247	Flexivest Fourteen Research Center	Bellville	Western Cape	South Africa	7530
248	Panorama Psychiatry and Memory Clinic	Panorama	Western Cape	South Africa	7500
249	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
250	Hospital Mutua de Terrassa	Terrassa	Barcelona	Spain	08221
251	Hospital Virgen del Puerto	Plasencia	Caceres	Spain	10600
252	Hospital Universitario Son Espases	Palma de Mallorca	Islas Baleares	Spain	07010
253	CLONUS	Palma de Mallorca	Islas Baleares	Spain	07014
254	Hospital de Donostia	San Sebastian	Pais Vasco	Spain	20014
255	Hospital de Cruces	Baracaldo	Vizcalla	Spain	48903
256	Hospital del Mar	Barcelona		Spain	08003
257	Fundacio ACE Institut Catala de Neurociences Aplicades	Barcelona		Spain	08014
258	Centro Internacional de Medicina Avanzda (CIMA)	Barcelona		Spain	08034
259	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
260	Hospital Divino Valles	Burgos		Spain	09006
261	Hospital de la Princesa	Madrid		Spain	28006
262	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
263	Hospital Clinico San Carlos	Madrid		Spain	28040
264	Hospital 12 de Octubre	Madrid		Spain	28041
265	Hospital Universitario La Paz	Madrid		Spain	28046
266	Hospital Universitario Virgen de la Arrixaca	Murcia		Spain	30120
267	Malmo University Hospital	Malmo		Sweden	21 224
268	Uppsala Imanet AB	Uppsala		Sweden	751 09
269	Akademiska Sjukhuset	Uppsala		Sweden	75185
270	ORKI, enheten for radiologi	Uppsala		Sweden	75185
271	Memory Clinic Neuro-Psychologie Zentrum	Basel	BS	Switzerland	CH-4031
272	Hopitaux Universitaires de Geneve	Les Acacias	GE	Switzerland	1227
273	CHUV Lausanne	Lausanne	VD	Switzerland	1005
274	Hopitaux Universitaires de Geneve	Thonex-Geneva		Switzerland	CH-1226
275	MAC UK Neuroscience Ltd	Blackpool	Lancashire	United Kingdom	FY2 0JH
276	MAC UK Neuroscience, Research Assessment Centre	Trafford Park	Manchester	United Kingdom	M32 0UT
277	Pollard Park Health Centre	Bradford		United Kingdom	BD3 0DQ
278	Clinical Investigation and Research Unit (CIRU)	Brighton		United Kingdom	BN2 5BE
279	Glasgow Memory Clinic	Glasgow		United Kingdom	G20 0XA
280	Kings College Hospital	London		United Kingdom	SE5 9RS
281	Dept. of Neurosciences Charing Cross Hospital	London		United Kingdom	W6 8RF
282	Newcastle General Hospital	Newcastle upon Tyne		United Kingdom	NE4 5PL
283	Northampton General Hospital	Northampton		United Kingdom	NN1 5BD
284	Llandough Hospital	Penarth		United Kingdom	CF64 2XX
285	Royal Hallamshire Hospital	Sheffield		United Kingdom	S10 2JF
286	Grenoside Grange Hospital	Sheffield		United Kingdom	S35 8QS
287	Victoria Hospital	Swindon		United Kingdom	SN3 6BW

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00676143
• Other Study ID Numbers: 3133K1-3001; B2521002; 2007-005995-14; NCT00909675
• First Posted: May 12, 2008
• Last Update Posted: Jun 10, 2016
• Last Verified: May 1, 2016

• Keywords provided by Pfizer: antibody; immunotherapy
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Recruitment Details	The study was conducted at 218 centers across the world. The study was terminated early by the sponsor on 06 August 2012. Enrollment had already been completed at the time of this decision. Participants who were still participating at that time were asked to complete an early withdrawal visit.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by intravenous (IV) infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks.	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Period Title: Overall Study
STARTED	441	658
Treated	439	654
COMPLETED	285	398
NOT COMPLETED	156	260

Baseline Characteristics

Arm/Group Title	Placebo	Bapineuzumab	Total
Arm/Group Description	Participants received placebo by intravenous (IV) infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks.	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Total of all reporting groups
Overall Participants	439	654	1093
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	70.3 (7.75)	71.0 (7.67)	70.7 (7.71)
Age, Customized (Number of participants) [Number]
<65 years	97 22.1%	132 20.2%	229 21%
>=65 years	342 77.9%	522 79.8%	864 79%
Sex: Female, Male (Count of Participants)
Female	262 59.7%	421 64.4%	683 62.5%
Male	177 40.3%	233 35.6%	410 37.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog)/11 Subscale Total Score at Week 78
Description	The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4) constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8) remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension. This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.
Time Frame	Baseline and 78 weeks

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and Disability Assessment for Dementia (DAD) total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	300	414
Least Squares Mean (Standard Error) [Unit on a scale]	7.31 (0.47)	7.32 (0.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments	Change in ADAS-Cog/11 total score was analyzed using a restricted maximum likelihood-based mixed model for repeated measures. The number of participants in each group gave 90% power to detect a 2.21 point advantage for the bapineuzumab group over placebo on the ADAS-Cog/11 total score, at the primary time point (Week 78). This calculation was based on a two-sided test with an alpha of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.979
	Comments	Primary variable ADAS-Cog/11 total score had to reach statistical significance, p-values had to reach p <=0.05, in order to be declared effective.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -1.18 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 78
Description	The DAD measures instrumental and basic activities of daily living in participants with Alzheimer's Disease (AD). The DAD is administered to the participants'caregiver in the form of an interview. This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced by the participant. This scale assesses a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. A total score is obtained by adding the rating for each question and converting this total score out of 100. Higher scores indicate better function; a positive change from baseline indicates an improvement.
Time Frame	Baseline and 78 weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	301	411
Least Squares Mean (Standard Deviation) [Unit on a scale]	-14.94 (1.00)	-14.89 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments	Change in DAD total score was analyzed using a restricted maximum likelihood-based mixed model for repeated measures. The number of participants in each group gave 90% power to detect a 5.39 unit advantage for the bapineuzumab group over placebo on the DAD total score, at the primary time point (Week 78). This calculation was based on a two-sided test with an alpha of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.973
	Comments	Primary variable DAD total score had to reach statistical significance, p-values had to reach p <=0.05, in order to be declared effective.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -2.51 to 2.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Brain Amyloid Burden at Week 71
Description	Brain amyloid burden as imaged by 11C-Pittsburgh compound B (PIB) positron emission tomography (PET). The latter is a semi-quantitative measure of the extent of fibrillar amyloid in the brain. PIB PET measurements were made in cortical regions found to have the highest burden of fibrillar amyloid at autopsy in participants diagnosed as having Alzheimer's pathology, and also regions reported to have the highest average retention of PIB signal in previous PET studies enrolling participants with probable AD. This parameter reflects overall brain amyloid deposition as indexed by imaging. The change from baseline was measured as average standard uptake value ratio (SUVr) in prespecified regions of interest (ROI) assessed by PIB PET imaging in a subset of participants.
Time Frame	Baseline and 71 weeks

Outcome Measure Data

Analysis Population Description

PIB PET population included all randomized participants who enrolled in the PET substudies and who met the following criteria: a) received at least one infusion or portion of an infusion of study drug, b) had a baseline and at least one postbaseline PIB PET assessment, and c) had an SUVr for the global cortical average (GCA) ROI ≥1.35 at baseline.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	12	15
Least Squares Mean (Standard Error) [standard uptake value ratio]	0.03 (0.04)	-0.04 (0.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments	Change in PIB PET SUVr was analyzed using a restricted maximum likelihood-based mixed model for repeated measures. The number of participants gave 90% power to detect a 0.152 unit advantage for the bapineuzumab group over placebo for PiB PET binding at Week 71. The calculations were based on 2-sided tests with alpha set at 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.159
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Cerebrospinal Fluid (CSF) Phospho-tau Levels at Week 71
Description	Biomarkers CSF phospho-tau is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD. Accordingly, a reduction from baseline in levels of CSF tau in participants who received bapineuzumab compared with participants who received placebo may be indicative of a reduction in neuronal loss in participants treated with bapineuzumab.
Time Frame	Baseline and 71 Weeks

Outcome Measure Data

Analysis Population Description

CSF population included all randomized participants who enrolled in the CSF substudies, received at least one infusion or portion of an infusion of study drug, and had a baseline and at least one postbaseline CSF measurement (CSF phospho-tau).

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	62	76
Least Squares Mean (Standard Error) [pg/mL]	0.83 (2.04)	-0.55 (1.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments	Change in CSF phospho-tau was analyzed using an analysis of covariance (ANCOVA) model. The analysis was based on the treatment difference estimated at Week 71 based on appropriate contrasts or LS means. The number of participants gave 90% power to detect a 13-ng/L advantage in phospho-tau for the bapineuzumab group over placebo at Week 71. The calculations were based on 2-sided tests with alpha set at 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.620
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.38
	Confidence Interval	(2-Sided) 95%; -6.89 to 4.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Brain Volume, as Assessed by Magnetic Resonance Imaging Brain Boundary Shift Integral (MRI BBSI), at Week 71
Description	Cerebral atrophy correlates closely with the gradual cognitive decline in AD and can be visualized by MRI. The BBSI technique involves positional matching of serial 3-dimensional MRI brain images, such that brain MRI-image volumes were first registered and then subtracted from each other. Atrophy rates would generally be expected to be lower if the underlying disease was attenuated by effective treatment.
Time Frame	Baseline and 71 Weeks

Outcome Measure Data

Analysis Population Description

vMRI population included all randomized participants who enrolled in the vMRI substudies, received at least one infusion or portion of an infusion of study drug, and had a baseline and at least one postbaseline vMRI that passed quality control and was satisfactory for volumetric analysis.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	131	197
Least Squares Mean (Standard Error) [Milliliter (mL)/year]	17.64 (0.69)	17.51 (0.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments	Change in MRI BBSI was analyzed using a restricted maximum likelihood-based mixed model for repeated measures. The number of participants gave 90% power to detect a 4.15-cm3 advantage for the bapineuzumab group over placebo on reduction in brain volume as measured by the BBSI at Week 71. The calculations were based on 2-sided tests with alpha set at 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.884
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -1.89 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78
Description	Treatment differences are estimated using least-squares (LS) means with factor levels weighted according to overall analysis population proportions. ADAS-Cog/11 total score range is 0 (least impairment) to 70 (most impairment); a negative treatment difference (bapineuzumab minus placebo) favors bapineuzumab. Within the MMRMs for ADAS-Cog/11 described for the primary analyses, linear contrasts were formed to test increasing trend of the differences between bapineuzumab and placebo from Week 39 (the 9-month visit) through Week 78 (the 18 -month visit) for each variable, which is equivalent to testing a positive slope of the differences between each bapineuzumab dose group and placebo from Week 39 through Week 78. Results are from a restricted maximum likelihood (REML)-based mixed model for MMRM.
Time Frame	Week 39 to Week 78

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab 0.5 mg/kg
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Week 39	2.95 (0.30)	2.68 (0.25)
Week 52	4.40 (0.34)	4.08 (0.29)
Week 65	5.76 (0.39)	5.16 (0.32)
Week 78	7.31 (0.47)	7.32 (0.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments	Treatment Difference: Bapineuzumab - Placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.700
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; -0.97 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Divergence of Effect on the DAD Total Scores From Week 39 to Week 78
Description	Treatment differences are estimated using least-squares (LS) means with factor levels weighted according to overall analysis population proportions. DAD total score range is 0 to 100; a positive treatment difference (bapineuzumab minus placebo) favors bapineuzumab. Within the MMRMs for ADAS-Cog/11 described for the primary analyses, linear contrasts were formed to test increasing trend of the differences between bapineuzumab and placebo from Week 39 (the 9-month visit) through Week 78 (the 18 -month visit) for each variable, which is equivalent to testing a positive slope of the differences between each bapineuzumab dose group and placebo from Week 39 through Week 78. Results are from a restricted maximum likelihood (REML)-based mixed model for MMRM.
Time Frame	Week 39 to Week 78

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab 0.5 mg/kg
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Week 39	-6.60 (0.65)	-6.93 (0.54)
Week 52	-9.34 (0.73)	-9.34 (0.61)
Week 65	-12.14 (0.91)	-13.04 (0.76)
Week 78	-14.94 (1.00)	-14.89 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments	Treatment Difference: Bapineuzumab - Placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.949
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -2.61 to 2.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Time to First Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan)
Description	The time to first median placebo deterioration, defined as the first time a participant experienced an increase (worsening) from baseline in ADAS-Cog/11 total score greater than or equal to the median worsening observed at Week 78 in the placebo group. The Kaplan Meier estimate of median time to first median placebo deterioration was presented.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Median (95% Confidence Interval) [Days]	463.0	457.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.684
	Comments
	Method	Log Rank
	Comments

9. Secondary Outcome

Title	Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan)
Description	The time to first clinically meaningful deterioration was defined as the first time a participant experienced an increase (worsening) from baseline in ADAS-Cog/11 total score of >=7.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Median (95% Confidence Interval) [Days]	NA	546.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.383
	Comments
	Method	Log Rank
	Comments

10. Secondary Outcome

Title	Time to First Median Placebo Deterioration on DAD Total Score (EU Analysis Plan)
Description	The time to first median placebo deterioration was defined as the first time a participant experienced a decrease (worsening) in DAD total score greater than or equal to the median worsening at Week 78 in the placebo group.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Median (95% Confidence Interval) [Days]	464.0	456.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.191
	Comments
	Method	Log Rank
	Comments

11. Secondary Outcome

Title	Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis)
Description	The time to first clinically meaningful deterioration was defined as the first time a participant experienced a decrease (worsening) from baseline in DAD total score of >=12.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Median (95% Confidence Interval) [Days]	546.0	546.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.478
	Comments
	Method	Log Rank
	Comments

12. Secondary Outcome

Title	Change From Baseline in Dependence Scale Total Score at Week 78
Description	The Dependence Scale (DS) is a 13-item, caregiver-rated instrument for determining the amount of support required by a participant with AD. The DS total score ranges from 0 to 15, with higher scores indicating more need for assistance. The DS was administered as an interview to the caregiver at scheduled study visits.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	316	437
Least Squares Mean (Standard Error) [Unit on a scale]	1.33 (0.12)	1.22 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments	Change in DS total score was analyzed using a restricted maximum likelihood-based mixed model for repeated measures.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.462
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (EU Analysis Plan)
Description	Percentage of participants with worsening from baseline to Week 78 in ADAS-Cog/11 total score of ≤0, ≤3, and ≤7 points were reported. In order to calculate time to first median placebo deterioration in ADAS-Cog/11, the median change from baseline to Week 78 among the placebo participants of the mITT analysis population were determined. The median changes were used as the cutpoints for determining "deterioration" for Alzheimer's disease participants in the study. If the median change from baseline to Week 78 in the ADAS-Cog/11 total score among the placebo participants of the mITT Analysis Population is 7 points, then the first median placebo deterioration is the first time where there is a worsening on the ADAS-Cog/11 total score of 7 points or more and the worsening is confirmed by the ADAS-Cog/11 assessment at the next non-missing visit.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Worsening of 0 points	18.3 4.2%	15.5 2.4%
Worsening of 3 points	30.4 6.9%	25.5 3.9%
Worsening of 7 points	42.5 9.7%	38.0 5.8%

14. Secondary Outcome

Title	Percentage of Responders for ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan)
Description	Percentage of participants whose increase (worsening) from baseline to Week 78 in ADAS-Cog/11 total score was <7.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Number [Percentage of participant]	42.2	37.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.086
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

15. Secondary Outcome

Title	Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (EU Analysis Plan)
Description	Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score of ≤ 0, ≤ 6, and ≤ 12 points. In order to calculate time to first median placebo deterioration in DAD, the median change from baseline to Week 78 among the placebo participants of the mITT analysis population were determined. The median changes were used as the cutpoints for determining "deterioration" for Alzheimer's disease participants in the study. If the median change from baseline to Week 78 in the DAD total score among the placebo participants of the mITT Analysis Population is 7 points, then the first median placebo deterioration is the first time where there is a worsening on the DAD total score of 7 points or more and the worsening is confirmed by the DAD assessment at the next non-missing visit.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Worsening of 0 points	17.2 3.9%	18.6 2.8%
Worsening of 6 points	29.9 6.8%	27.4 4.2%
Worsening of 12 points	39.7 9%	34.9 5.3%

16. Secondary Outcome

Title	Percentage of Responders for DAD Total Score at Week 78 (US Analysis Plan)
Description	Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score was <12.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	431	650
Number [Percentage of participant]	39.7	34.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.120
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

17. Secondary Outcome

Title	Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78
Description	The CDR-SOB is a global clinical staging instrument that sums 6 clinical ratings: 1) memory, 2) orientation, 3) judgment and problem solving, 4) involvement in community affairs, 5) home and hobbies, and 6) personal care based on the Clinical Dementia Rating Scale (CDR) interview. The CDR includes discussions with the participant and caregiver using a structured format. This scale had to be administered by a trained and certified global rater who did not have access to any information regarding adverse events experienced by the participant. CDR-SOB total score range is 0 (least impairment) to 18 (most impairment); a negative change from baseline indicates an improvement.
Time Frame	Baseline and 78 Weeks

Outcome Measure Data

Analysis Population Description

The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Arm/Group Title	Placebo	Bapineuzumab
Arm/Group Description	Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Measure Participants	310	427
Least Squares Mean (Standard Error) [Units on a scale]	2.59 (0.16)	2.44 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bapineuzumab
	Comments	Change in CDR-SOB total score was analyzed using a restricted maximum likelihood-based mixed model for repeated measures.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.448
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.55 to 0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	4 years
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Placebo		Bapineuzumab
Arm/Group Description	Participants received placebo by intravenous (IV) infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks.		Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
All Cause Mortality
	Placebo		Bapineuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Bapineuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/439 (17.5%)		137/654 (20.9%)
Blood and lymphatic system disorders
Anaemia	1/439 (0.2%)	1	0/654 (0%)	0
Bone marrow failure	0/439 (0%)	0	1/654 (0.2%)	1
Leukocytosis	1/439 (0.2%)	1	0/654 (0%)	0
Cardiac disorders
Acute myocardial infarction	1/439 (0.2%)	1	0/654 (0%)	0
Angina pectoris	2/439 (0.5%)	3	1/654 (0.2%)	1
Angina unstable	0/439 (0%)	0	1/654 (0.2%)	1
Atrial fibrillation	0/439 (0%)	0	1/654 (0.2%)	1
Atrioventricular block complete	0/439 (0%)	0	2/654 (0.3%)	2
Atrioventricular block second degree	0/439 (0%)	0	1/654 (0.2%)	1
Bradycardia	1/439 (0.2%)	1	1/654 (0.2%)	1
Cardiac arrest	1/439 (0.2%)	1	1/654 (0.2%)	1
Cardiovascular insufficiency	1/439 (0.2%)	1	0/654 (0%)	0
Hypertensive heart disease	1/439 (0.2%)	1	0/654 (0%)	0
Myocardial infarction	1/439 (0.2%)	1	0/654 (0%)	0
Myocardial ischaemia	0/439 (0%)	0	1/654 (0.2%)	1
Sinus bradycardia	1/439 (0.2%)	1	0/654 (0%)	0
Supraventricular tachycardia	1/439 (0.2%)	1	1/654 (0.2%)	1
Tachycardia	1/439 (0.2%)	1	0/654 (0%)	0
Eye disorders
Cataract	0/439 (0%)	0	2/654 (0.3%)	2
Vitreous haemorrhage	0/439 (0%)	0	1/654 (0.2%)	1
Gastrointestinal disorders
Abdominal pain	1/439 (0.2%)	1	1/654 (0.2%)	1
Abdominal pain upper	0/439 (0%)	0	1/654 (0.2%)	1
Anal haemorrhage	0/439 (0%)	0	1/654 (0.2%)	1
Colonic polyp	1/439 (0.2%)	1	0/654 (0%)	0
Diarrhoea	0/439 (0%)	0	1/654 (0.2%)	1
Duodenal ulcer perforation	0/439 (0%)	0	1/654 (0.2%)	3
Gastric ulcer	0/439 (0%)	0	1/654 (0.2%)	1
Gastrointestinal ulcer haemorrhage	0/439 (0%)	0	1/654 (0.2%)	1
Haematemesis	1/439 (0.2%)	1	0/654 (0%)	0
Ileus	0/439 (0%)	0	1/654 (0.2%)	1
Inguinal hernia	2/439 (0.5%)	2	0/654 (0%)	0
Inguinal hernia, obstructive	1/439 (0.2%)	1	0/654 (0%)	0
Intestinal obstruction	1/439 (0.2%)	1	0/654 (0%)	0
Nausea	0/439 (0%)	0	2/654 (0.3%)	2
Oesophageal ulcer	0/439 (0%)	0	1/654 (0.2%)	1
Pancreatitis	0/439 (0%)	0	1/654 (0.2%)	1
Pancreatitis acute	0/439 (0%)	0	1/654 (0.2%)	1
Vomiting	0/439 (0%)	0	1/654 (0.2%)	1
General disorders
Chest discomfort	1/439 (0.2%)	1	0/654 (0%)	0
Chest pain	1/439 (0.2%)	1	2/654 (0.3%)	2
Device occlusion	0/439 (0%)	0	1/654 (0.2%)	1
Fibrosis	0/439 (0%)	0	1/654 (0.2%)	1
General physical health deterioration	0/439 (0%)	0	1/654 (0.2%)	2
Malaise	1/439 (0.2%)	1	0/654 (0%)	0
Non-cardiac chest pain	1/439 (0.2%)	1	0/654 (0%)	0
Pain	1/439 (0.2%)	1	0/654 (0%)	0
Pyrexia	0/439 (0%)	0	2/654 (0.3%)	2
Hepatobiliary disorders
Bile duct stone	1/439 (0.2%)	1	0/654 (0%)	0
Cholangitis	0/439 (0%)	0	1/654 (0.2%)	1
Cholecystitis	1/439 (0.2%)	1	1/654 (0.2%)	1
Cholelithiasis	0/439 (0%)	0	1/654 (0.2%)	1
Gallbladder disorder	0/439 (0%)	0	1/654 (0.2%)	1
Hepatic function abnormal	0/439 (0%)	0	1/654 (0.2%)	1
Jaundice	0/439 (0%)	0	1/654 (0.2%)	1
Immune system disorders
Hypersensitivity	0/439 (0%)	0	1/654 (0.2%)	1
Infections and infestations
Abdominal abscess	0/439 (0%)	0	1/654 (0.2%)	1
Abscess	0/439 (0%)	0	1/654 (0.2%)	1
Appendicitis	0/439 (0%)	0	2/654 (0.3%)	2
Bacterial Sepsis	0/439 (0%)	0	1/654 (0.2%)	1
Bronchitis	0/439 (0%)	0	1/654 (0.2%)	1
Cellulitis	0/439 (0%)	0	1/654 (0.2%)	1
Gastroenteritis	1/439 (0.2%)	1	1/654 (0.2%)	1
Herpes zoster	1/439 (0.2%)	1	0/654 (0%)	0
Infected skin ulcer	1/439 (0.2%)	1	0/654 (0%)	0
Kidney infection	0/439 (0%)	0	1/654 (0.2%)	1
Lower respiratory tract infection	1/439 (0.2%)	1	0/654 (0%)	0
Meningitis cryptococcal	1/439 (0.2%)	1	0/654 (0%)	0
Osteomyelitis	0/439 (0%)	0	1/654 (0.2%)	1
Paronychia	1/439 (0.2%)	1	0/654 (0%)	0
Pneumonia	3/439 (0.7%)	3	6/654 (0.9%)	6
Pseudomembranous colitis	1/439 (0.2%)	1	0/654 (0%)	0
Pyelonephritis	1/439 (0.2%)	1	0/654 (0%)	0
Sepsis	3/439 (0.7%)	4	1/654 (0.2%)	1
Toxic shock syndrome	0/439 (0%)	0	1/654 (0.2%)	1
Urinary tract infection	2/439 (0.5%)	2	2/654 (0.3%)	2
Urosepsis	0/439 (0%)	0	1/654 (0.2%)	1
Vaginitis bacterial	1/439 (0.2%)	1	0/654 (0%)	0
Viral upper respiratory tract infection	1/439 (0.2%)	1	0/654 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	1/439 (0.2%)	1	2/654 (0.3%)	3
Ankle fracture	0/439 (0%)	0	1/654 (0.2%)	1
Contusion	1/439 (0.2%)	1	0/654 (0%)	0
Drug administration error	0/439 (0%)	0	1/654 (0.2%)	1
Excoriation	0/439 (0%)	0	1/654 (0.2%)	1
Eye injury	0/439 (0%)	0	1/654 (0.2%)	1
Fall	1/439 (0.2%)	2	2/654 (0.3%)	2
Femoral neck fracture	0/439 (0%)	0	2/654 (0.3%)	5
Femur fracture	1/439 (0.2%)	1	3/654 (0.5%)	3
Head injury	0/439 (0%)	0	1/654 (0.2%)	1
Hip fracture	2/439 (0.5%)	5	1/654 (0.2%)	1
Humerus fracture	0/439 (0%)	0	1/654 (0.2%)	3
Post lumbar puncture syndrome	1/439 (0.2%)	1	0/654 (0%)	0
Pubis fracture	0/439 (0%)	0	1/654 (0.2%)	1
Radius fracture	2/439 (0.5%)	3	0/654 (0%)	0
Rib fracture	1/439 (0.2%)	3	0/654 (0%)	0
Spinal compression fracture	2/439 (0.5%)	7	1/654 (0.2%)	1
Stab wound	1/439 (0.2%)	1	0/654 (0%)	0
Subdural haematoma	1/439 (0.2%)	1	0/654 (0%)	0
Upper limb fracture	1/439 (0.2%)	2	0/654 (0%)	0
Wrist fracture	2/439 (0.5%)	5	0/654 (0%)	0
Investigations
Blood pressure increased	1/439 (0.2%)	2	0/654 (0%)	0
Fibrin D dimer increased	1/439 (0.2%)	1	0/654 (0%)	0
Heart rate increased	1/439 (0.2%)	1	0/654 (0%)	0
Streptococcus test positive	0/439 (0%)	0	1/654 (0.2%)	1
Metabolism and nutrition disorders
Dehydration	2/439 (0.5%)	2	3/654 (0.5%)	4
Hypoglycaemia	1/439 (0.2%)	1	0/654 (0%)	0
Hypokalaemia	0/439 (0%)	0	1/654 (0.2%)	1
Hyponatraemia	0/439 (0%)	0	2/654 (0.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/439 (0.2%)	1	0/654 (0%)	0
Arthritis	0/439 (0%)	0	1/654 (0.2%)	1
Back pain	1/439 (0.2%)	1	2/654 (0.3%)	2
Intervertebral disc protrusion	0/439 (0%)	0	1/654 (0.2%)	1
Lumbar spinal stenosis	0/439 (0%)	0	1/654 (0.2%)	1
Osteoarthritis	1/439 (0.2%)	1	1/654 (0.2%)	1
Polymyalgia rheumatica	0/439 (0%)	0	1/654 (0.2%)	1
Rhabdomyolysis	2/439 (0.5%)	2	2/654 (0.3%)	2
Spinal column stenosis	1/439 (0.2%)	1	0/654 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	0/439 (0%)	0	1/654 (0.2%)	1
Basal cell carcinoma	0/439 (0%)	0	1/654 (0.2%)	1
Bladder cancer	1/439 (0.2%)	1	0/654 (0%)	0
Breast cancer	2/439 (0.5%)	2	2/654 (0.3%)	2
Breast neoplasm	1/439 (0.2%)	1	0/654 (0%)	0
Hepatic neoplasm	1/439 (0.2%)	1	0/654 (0%)	0
Leiomyosarcoma	0/439 (0%)	0	1/654 (0.2%)	1
Lentigo maligna	0/439 (0%)	0	1/654 (0.2%)	1
Metastatic neoplasm	0/439 (0%)	0	1/654 (0.2%)	1
Neoplasm prostate	1/439 (0.2%)	1	0/654 (0%)	0
Oesophageal carcinoma	1/439 (0.2%)	1	0/654 (0%)	0
Prostate cancer	4/439 (0.9%)	5	1/654 (0.2%)	1
Squamous cell carcinoma	3/439 (0.7%)	3	0/654 (0%)	0
Nervous system disorders
Amyotrophic lateral sclerosis	0/439 (0%)	0	1/654 (0.2%)	5
Aphasia	0/439 (0%)	0	1/654 (0.2%)	1
Brain stem ischaemia	1/439 (0.2%)	1	0/654 (0%)	0
Cerebral haemorrhage	1/439 (0.2%)	1	3/654 (0.5%)	3
Cerebral haemosiderin deposition	1/439 (0.2%)	1	0/654 (0%)	0
Cerebral infarction	1/439 (0.2%)	1	0/654 (0%)	0
Cerebral ischaemia	0/439 (0%)	0	1/654 (0.2%)	1
Cerebral microhaemorrhage	0/439 (0%)	0	4/654 (0.6%)	4
Cerebrovascular accident	1/439 (0.2%)	2	0/654 (0%)	0
Convulsion	0/439 (0%)	0	3/654 (0.5%)	3
Dizziness	0/439 (0%)	0	1/654 (0.2%)	2
Epilepsy	0/439 (0%)	0	1/654 (0.2%)	1
Grand mal convulsion	1/439 (0.2%)	1	2/654 (0.3%)	2
Haemorrhagic stroke	1/439 (0.2%)	1	0/654 (0%)	0
Hydrocephalus	0/439 (0%)	0	1/654 (0.2%)	1
Ischaemic stroke	0/439 (0%)	0	2/654 (0.3%)	3
Lacunar infarction	1/439 (0.2%)	4	0/654 (0%)	0
Lethargy	0/439 (0%)	0	1/654 (0.2%)	1
Loss of consciousness	0/439 (0%)	0	1/654 (0.2%)	1
Mental impairment	0/439 (0%)	0	1/654 (0.2%)	1
Paraesthesia	0/439 (0%)	0	1/654 (0.2%)	1
Presyncope	0/439 (0%)	0	1/654 (0.2%)	1
Syncope	2/439 (0.5%)	2	4/654 (0.6%)	4
Transient ischaemic attack	0/439 (0%)	0	1/654 (0.2%)	1
Vasogenic cerebral oedema	4/439 (0.9%)	5	40/654 (6.1%)	61
Visual field defect	0/439 (0%)	0	1/654 (0.2%)	1
Agitation	1/439 (0.2%)	3	2/654 (0.3%)	2
Psychiatric disorders
Abnormal behaviour	1/439 (0.2%)	1	0/654 (0%)	0
Aggression	1/439 (0.2%)	1	0/654 (0%)	0
Completed suicide	0/439 (0%)	0	1/654 (0.2%)	1
Confusional state	2/439 (0.5%)	2	3/654 (0.5%)	3
Delirium	1/439 (0.2%)	2	2/654 (0.3%)	2
Depression	1/439 (0.2%)	1	0/654 (0%)	0
Hallucination	1/439 (0.2%)	1	1/654 (0.2%)	1
Mental status changes	2/439 (0.5%)	2	3/654 (0.5%)	3
Restlessness	1/439 (0.2%)	1	0/654 (0%)	0
Suicide attempt	1/439 (0.2%)	1	0/654 (0%)	0
Renal and urinary disorders
Acute prerenal failure	0/439 (0%)	0	1/654 (0.2%)	1
Haematuria	0/439 (0%)	0	1/654 (0.2%)	1
Pollakiuria	0/439 (0%)	0	1/654 (0.2%)	1
Renal failure acute	1/439 (0.2%)	1	2/654 (0.3%)	2
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/439 (0%)	0	1/654 (0.2%)	1
Breast mass	1/439 (0.2%)	1	1/654 (0.2%)	1
Rectocele	1/439 (0.2%)	1	0/654 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/439 (0%)	0	1/654 (0.2%)	1
Paranasal cyst	1/439 (0.2%)	1	0/654 (0%)	0
Pneumonia aspiration	1/439 (0.2%)	2	1/654 (0.2%)	1
Pulmonary embolism	2/439 (0.5%)	2	3/654 (0.5%)	3
Pulmonary oedema	1/439 (0.2%)	1	3/654 (0.5%)	3
Respiratory failure	1/439 (0.2%)	1	0/654 (0%)	0
Social circumstances
Social problem	0/439 (0%)	0	1/654 (0.2%)	1
Surgical and medical procedures
Thyroidectomy	0/439 (0%)	0	1/654 (0.2%)	1
Vascular disorders
Arteriosclerosis	1/439 (0.2%)	1	0/654 (0%)	0
Deep vein thrombosis	1/439 (0.2%)	1	5/654 (0.8%)	5
Ischaemia	0/439 (0%)	0	1/654 (0.2%)	1
Peripheral artery stenosis	0/439 (0%)	0	1/654 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Bapineuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	198/439 (45.1%)		298/654 (45.6%)
Gastrointestinal disorders
Diarrhoea	23/439 (5.2%)	30	34/654 (5.2%)	38
Infections and infestations
Nasopharyngitis	34/439 (7.7%)	40	45/654 (6.9%)	66
Urinary tract infection	24/439 (5.5%)	37	30/654 (4.6%)	34
Injury, poisoning and procedural complications
Fall	27/439 (6.2%)	36	39/654 (6%)	47
Nervous system disorders
Cerebral microhaemorrhage	16/439 (3.6%)	38	76/654 (11.6%)	218
Dizziness	23/439 (5.2%)	32	20/654 (3.1%)	26
Headache	44/439 (10%)	98	45/654 (6.9%)	66
Vasogenic cerebral oedema	5/439 (1.1%)	5	74/654 (11.3%)	123
Psychiatric disorders
Anxiety	26/439 (5.9%)	29	30/654 (4.6%)	61
Depression	27/439 (6.2%)	73	35/654 (5.4%)	95
Vascular disorders
Hypertension	22/439 (5%)	50	18/654 (2.8%)	48

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.