Study Evaluating Single Ascending Doses of AAB-001 Vaccine SAD Japanese Patients With Alzheimers Disease

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00397891
• Collaborator: (none)
• Enrollment: 80
• Locations: 4
• Arms: 3
• Duration (Months): 40
• Patients Per Site: 20
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Evaluate safety, tolerability, and pharmacokinetics of single doses of the investigational AAB-001 Vaccine in Japanese patients with Alzheimer's disease.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: bapineuzumab; Drug: bapineuzumab; Drug: bapineuzumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Safety, Tolerability, and Pharmakokinetic Study of Single Ascending Doses of AAB-001 in Japanese Patients With Mild to Moderate Alzheimer's Disease
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 bapineuzumab 0.15 mg/kg or placebo	Drug: bapineuzumab; The dose cohorts are as follows: 0.15 mg/kg AAB-001; 0.5 mg/kg AAB-001; 1.0 mg/kg AAB-001. Placebo is vehicle (all ingredients except active). In each dose cohort, designated as groups 1 to 3, study drug (AAB-001 or placebo) will be administered as an intravenous infusion over 1 hour.
Experimental: 2 bapineuzumab 0.5 mg/kg or placebo	Drug: bapineuzumab; The dose cohorts are as follows: 0.15 mg/kg AAB-001; 0.5 mg/kg AAB-001; 1.0 mg/kg AAB-001. Placebo is vehicle (all ingredients except active). In each dose cohort, designated as groups 1 to 3, study drug (AAB-001 or placebo) will be administered as an intravenous infusion over 1 hour.
Experimental: 3 bapineuzumab 1.0 mg/kg or placebo	Drug: bapineuzumab; The dose cohorts are as follows: 0.15 mg/kg AAB-001; 0.5 mg/kg AAB-001; 1.0 mg/kg AAB-001. Placebo is vehicle (all ingredients except active). In each dose cohort, designated as groups 1 to 3, study drug (AAB-001 or placebo) will be administered as an intravenous infusion over 1 hour.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Baseline up to Week 52]

   An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between dose of study medication and up to 52 weeks after the dose that were absent before treatment or that worsened relative to pre-treatment state.

2. Number of Participants With Clinically Significant Changes in Physical Examinations [Screening up to Week 52]

   Physical examination included the assessment of abdomen, back/spinal, breasts, external genitalia, extremities, general appearance, head, eyes, ears, nose, throat (HEENT), heart, lungs, lymph nodes and skin.

3. Number of Participants With Vital Signs of Potential Clinical Importance [Baseline up to Week 52]

   Criteria for determining potentially clinically important (PCI) vital signs was described as: supine blood pressure (BP)- systolic (greater than or equal to [>=]160 millimeter mercury [mm Hg] or less than or equal to [<=]90 mm Hg and increase or decrease of >=20 mm Hg compared to baseline value), supine diastolic BP (>=100 mm Hg or <= 50 mm Hg and increase or decrease of >=15 mm Hg compared to baseline value), supine pulse rate (>=120 beats per minute (bpm) or <=45 bpm and increase or decrease of >15 bpm compared to baseline value), body temperature (>38.3 degree Celsius and <35 degree Celsius).

4. Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance [Screening up to Week 16]

   Criteria for determining PCI ECG result was described as: heart rate (>=120 bpm or <=45 bpm and increase or decrease of >15 bpm compared to baseline value), PR interval (>=220 millisecond (msec) and change of >=20 msec compared to baseline value), QRS interval (>=120 msec), corrected QT (QTc) interval for men (>450 msec), QTc interval for women (>470 msec).

5. Number of Participants With Laboratory Test Results of Potential Clinical Importance [Week 1 up to Week 52]

   Criteria for PCI laboratory results: hematology (hematocrit [decrease >=5%], hemoglobin [decrease >=20gram/liter {g/L}] from baseline, white blood cells [<3], neutrophils [<1.5], platelet [<100], eosinophils [>0.5] *10^9/L); blood chemistry (sodium [>5], potassium [>0.5], fasting glucose [>0.83], phosphorous [>0.162] millimole/L [mmol/L] above upper limit of normal [ULN] and below lower limit of normal [LLN], non-fasting glucose >5 mmol/L above ULN, >0.56 mmol/L below LLN, creatinine >1.36*ULN, blood urea nitrogen >1.5*ULN, calcium [change of >=0.25 mmol/L], total protein [change of >=20g/L], albumin [change of >=10g/L], uric acid [change of >0.119mmol/L] from baseline and outside normal limits); Liver function tests (alanine aminotransferase/serum glutamic pyruvic transaminase [ALT/SGPT] and aspartate aminotransferase/serum glutamic oxaloacetic transaminase [AST/SGOT] >2*ULN, total bilirubin >2*ULN, alkaline phosphatase >1.5*ULN, gamma-glutamyl-transpeptidase [GGT] >3*ULN).

6. Number of Participants With Clinically Significant Changes in Neurological Examinations [Screening up to Week 52]

   Neurological examination included the assessment of mental status, cranial nerves, visual fields, sensory, motor, gait, primitive reflexes and tendon reflexes.

7. Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 [Baseline, Week 6]

   MMSE measures general cognitive functioning: orientation to time (range: 0 to 5) and orientation to place (range: 0 to 5), registration of 3 words (range: 0 to 3), attention and calculation (range: 0 to 5), recall of 3 words (range: 0 to 3), naming (range: 0 to 2), repetition (range: 0 to 1), comprehension (range: 0 to 3), reading (range: 0 to 1), writing (range: 0 to 1) and drawing (range: 0 to 1). Total score is the sum of sub-scores; total score ranges from 0 to 30, higher score indicates better cognitive state.

8. Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 16 [Baseline, Week 16]

   MMSE measures general cognitive functioning: orientation to time (range: 0 to 5) and orientation to place (range: 0 to 5), registration of 3 words (range: 0 to 3), attention and calculation (range: 0 to 5), recall of 3 words (range: 0 to 3), naming (range: 0 to 2), repetition (range: 0 to 1), comprehension (range: 0 to 3), reading (range: 0 to 1), writing (range: 0 to 1) and drawing (range: 0 to 1). Total score is the sum of sub-scores; total score ranges from 0 to 30, higher score indicates better cognitive state.

9. Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 52 [Baseline, Week 52]

   MMSE measures general cognitive functioning: orientation to time (range: 0 to 5) and orientation to place (range: 0 to 5), registration of 3 words (range: 0 to 3), attention and calculation (range: 0 to 5), recall of 3 words (range: 0 to 3), naming (range: 0 to 2), repetition (range: 0 to 1), comprehension (range: 0 to 3), reading (range: 0 to 1), writing (range: 0 to 1) and drawing (range: 0 to 1). Total score is the sum of sub-scores; total score ranges from 0 to 30, higher score indicates better cognitive state.

Secondary Outcome Measures

1. Maximum Observed Serum Concentration (Cmax) of Bapineuzumab [0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52]

   Participants who received bapineuzumab were reported.

2. Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab [0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52]

   Participants who received bapineuzumab were reported.

3. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Bapineuzumab [0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52]

   AUC is a measure of the serum concentration of the drug over time. AUC (0-t) is area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). Participants who received bapineuzumab were reported.

4. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab [0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52]

   AUC is a measure of the serum concentration of the drug over time. AUC (0 - ∞) is area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). Participants who received bapineuzumab were reported.

5. Systemic Clearance (CL) of Bapineuzumab [0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52]

   CL is a quantitative measure of the rate at which a drug substance is removed from the body. Participants who received bapineuzumab were reported.

6. Volume of Distribution at Steady State (Vss) of Bapineuzumab [0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52]

   Volume of distribution is defined as the theoretical blood volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Participants who received bapineuzumab were reported.

7. Mean Residence Time of Bapineuzumab [0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52]

   MRT is average time for which the drug molecules resides in the body, after administration. It is calculated as area under the serum concentration versus time first moment curve from time zero (pre-dose) to extrapolated infinite time (AUMC [0 - ∞]) divided by area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (AUC[0 - ∞]). AUMC (0-∞) is calculated as AUMC(0-inf)= AUMCt + [(t x Ct) / kel] + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method, Ct is the concentration at time t and kel is the terminal phase rate constant. Participants who received bapineuzumab were reported.

8. Serum Decay Half-Life (t1/2) of Bapineuzumab [0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52]

   Serum decay half-life is the time measured for the serum concentration to decrease by one half. Participants who received bapineuzumab were reported.

9. Serum Bapineuzumab Concentrations [0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6, 24, 48, 168, 336, 672, 1008, 1344, 1848, 2184, 2688, 4368, 8736 hours post start of infusion]

   Serum bapineuzumab concentration was determined by using a validated enzyme-linked immunosorbent assay (ELISA) method. Participants who received bapineuzumab were reported.

10. Number of Participants With Positive Serum Anti-Bapineuzumab Antibody [Baseline (Day 1) up to Week 52]

    Serum anti-bapineuzumab antibody concentration was determined by using a validated ELISA method.

11. Plasma Amyloid-beta (x-40) Concentrations [0 (pre-infusion), 1, 6, 24, 336, 1008, 2184, 2688, 4368, 8736 hours post start of infusion]

    Amyloid-beta (A-beta) is a peptide fragment of the amyloid precursor protein which is one of the characteristic hallmarks of Alzheimer's disease (AD). Total plasma amyloid-beta (x-40) was determined using a validated ELISA method.

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 AD

• Age 50-85

• MMSE 14-26

• Other Inclusion Criteria Apply

Exclusion Criteria:

• Significant Neurological Disease

• Major Psychiatric Disorder

• Clinically Significant Systemic Illness

• Other Exclusion Criteria Apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Chiba		Japan
2	Pfizer Investigational Site	Saitama		Japan
3	Pfizer Investigational Site	Shizuoka		Japan
4	Pfizer Investigational Site	Tokyo		Japan

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of 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: Wyeth is now a wholly owned subsidiary of Pfizer
• ClinicalTrials.gov Identifier: NCT00397891
• Other Study ID Numbers: 3133K1-102
• First Posted: Nov 10, 2006
• Last Update Posted: Sep 4, 2014
• Last Verified: Aug 1, 2014

• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Period Title: Overall Study
STARTED	6	6	6	6	8
COMPLETED	5	6	6	6	7
NOT COMPLETED	1	0	0	0	1

Baseline Characteristics

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo	Total
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.	Total of all reporting groups
Overall Participants	6	6	6	6	8	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.67 (5.16)	72.17 (8.38)	72.17 (10.87)	64.83 (5.19)	68.75 (8.89)	67.78 (8.72)
Sex: Female, Male (Count of Participants)
Female	3 50%	1 16.7%	3 50%	3 50%	4 50%	14 43.8%
Male	3 50%	5 83.3%	3 50%	3 50%	4 50%	18 56.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between dose of study medication and up to 52 weeks after the dose that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

Safety data set included all randomized participants who received at least 1 dose of study medication.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	8
AEs	5 83.3%	3 50%	6 100%	3 50%	7 87.5%
SAEs	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Physical Examinations
Description	Physical examination included the assessment of abdomen, back/spinal, breasts, external genitalia, extremities, general appearance, head, eyes, ears, nose, throat (HEENT), heart, lungs, lymph nodes and skin.
Time Frame	Screening up to Week 52

Outcome Measure Data

Analysis Population Description

Safety data set included all randomized participants who received at least 1 dose of study medication.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	8
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Vital Signs of Potential Clinical Importance
Description	Criteria for determining potentially clinically important (PCI) vital signs was described as: supine blood pressure (BP)- systolic (greater than or equal to [>=]160 millimeter mercury [mm Hg] or less than or equal to [<=]90 mm Hg and increase or decrease of >=20 mm Hg compared to baseline value), supine diastolic BP (>=100 mm Hg or <= 50 mm Hg and increase or decrease of >=15 mm Hg compared to baseline value), supine pulse rate (>=120 beats per minute (bpm) or <=45 bpm and increase or decrease of >15 bpm compared to baseline value), body temperature (>38.3 degree Celsius and <35 degree Celsius).
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

Safety data set included all randomized participants who received at least 1 dose of study medication.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	8
Number [participants]	2 33.3%	0 0%	2 33.3%	1 16.7%	1 12.5%

4. Primary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance
Description	Criteria for determining PCI ECG result was described as: heart rate (>=120 bpm or <=45 bpm and increase or decrease of >15 bpm compared to baseline value), PR interval (>=220 millisecond (msec) and change of >=20 msec compared to baseline value), QRS interval (>=120 msec), corrected QT (QTc) interval for men (>450 msec), QTc interval for women (>470 msec).
Time Frame	Screening up to Week 16

Outcome Measure Data

Analysis Population Description

Safety data set included all randomized participants who received at least 1 dose of study medication.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	8
Number [participants]	0 0%	0 0%	0 0%	0 0%	1 12.5%

5. Primary Outcome

Title	Number of Participants With Laboratory Test Results of Potential Clinical Importance
Description	Criteria for PCI laboratory results: hematology (hematocrit [decrease >=5%], hemoglobin [decrease >=20gram/liter {g/L}] from baseline, white blood cells [<3], neutrophils [<1.5], platelet [<100], eosinophils [>0.5] *10^9/L); blood chemistry (sodium [>5], potassium [>0.5], fasting glucose [>0.83], phosphorous [>0.162] millimole/L [mmol/L] above upper limit of normal [ULN] and below lower limit of normal [LLN], non-fasting glucose >5 mmol/L above ULN, >0.56 mmol/L below LLN, creatinine >1.36*ULN, blood urea nitrogen >1.5*ULN, calcium [change of >=0.25 mmol/L], total protein [change of >=20g/L], albumin [change of >=10g/L], uric acid [change of >0.119mmol/L] from baseline and outside normal limits); Liver function tests (alanine aminotransferase/serum glutamic pyruvic transaminase [ALT/SGPT] and aspartate aminotransferase/serum glutamic oxaloacetic transaminase [AST/SGOT] >2*ULN, total bilirubin >2*ULN, alkaline phosphatase >1.5*ULN, gamma-glutamyl-transpeptidase [GGT] >3*ULN).
Time Frame	Week 1 up to Week 52

Outcome Measure Data

Analysis Population Description

Safety data set included all randomized participants who received at least 1 dose of study medication.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	8
Number [participants]	6 100%	4 66.7%	3 50%	5 83.3%	5 62.5%

6. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Neurological Examinations
Description	Neurological examination included the assessment of mental status, cranial nerves, visual fields, sensory, motor, gait, primitive reflexes and tendon reflexes.
Time Frame	Screening up to Week 52

Outcome Measure Data

Analysis Population Description

Safety data set included all randomized participants who received at least 1 dose of study medication.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	8
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%

7. Primary Outcome

Title	Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6
Description	MMSE measures general cognitive functioning: orientation to time (range: 0 to 5) and orientation to place (range: 0 to 5), registration of 3 words (range: 0 to 3), attention and calculation (range: 0 to 5), recall of 3 words (range: 0 to 3), naming (range: 0 to 2), repetition (range: 0 to 1), comprehension (range: 0 to 3), reading (range: 0 to 1), writing (range: 0 to 1) and drawing (range: 0 to 1). Total score is the sum of sub-scores; total score ranges from 0 to 30, higher score indicates better cognitive state.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

Safety data set included all randomized participants who received at least 1 dose of study medication.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	8
Baseline	16.8 (2.9)	21.0 (3.6)	21.0 (4.6)	20.2 (2.8)	20.6 (3.0)
Change at Week 6	-0.2 (2.1)	0.0 (2.3)	-0.3 (3.0)	-0.2 (3.8)	-1.9 (3.1)

8. Primary Outcome

Title	Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 16
Description	MMSE measures general cognitive functioning: orientation to time (range: 0 to 5) and orientation to place (range: 0 to 5), registration of 3 words (range: 0 to 3), attention and calculation (range: 0 to 5), recall of 3 words (range: 0 to 3), naming (range: 0 to 2), repetition (range: 0 to 1), comprehension (range: 0 to 3), reading (range: 0 to 1), writing (range: 0 to 1) and drawing (range: 0 to 1). Total score is the sum of sub-scores; total score ranges from 0 to 30, higher score indicates better cognitive state.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Safety data set included all randomized participants who received at least 1 dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	7
Mean (Standard Deviation) [units on a scale]	0.2 (2.9)	-0.7 (4.1)	0.7 (2.4)	-0.3 (2.4)	-1.4 (2.6)

9. Primary Outcome

Title	Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 52
Description	MMSE measures general cognitive functioning: orientation to time (range: 0 to 5) and orientation to place (range: 0 to 5), registration of 3 words (range: 0 to 3), attention and calculation (range: 0 to 5), recall of 3 words (range: 0 to 3), naming (range: 0 to 2), repetition (range: 0 to 1), comprehension (range: 0 to 3), reading (range: 0 to 1), writing (range: 0 to 1) and drawing (range: 0 to 1). Total score is the sum of sub-scores; total score ranges from 0 to 30, higher score indicates better cognitive state.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Safety data set included all randomized participants who received at least 1 dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	5	6	6	6	7
Mean (Standard Deviation) [units on a scale]	-2.4 (1.9)	-3.8 (6.4)	-0.7 (2.7)	-1.2 (5.6)	-2.9 (1.3)

10. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of Bapineuzumab
Description	Participants who received bapineuzumab were reported.
Time Frame	0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6
Mean (Standard Deviation) [microgram per milliliter (mcg/mL)]	3.32 (0.857)	11.1 (1.16)	21.0 (0.968)	61.0 (32.8)

11. Secondary Outcome

Title	Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab
Description	Participants who received bapineuzumab were reported.
Time Frame	0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6
Median (Full Range) [hours]	1.51	1.54	1.53	1.71

12. Secondary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Bapineuzumab
Description	AUC is a measure of the serum concentration of the drug over time. AUC (0-t) is area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). Participants who received bapineuzumab were reported.
Time Frame	0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6
Mean (Standard Deviation) [mcg*hour/mL]	1260 (254)	4264 (462)	7818 (652)	15313 (8478)

13. Secondary Outcome

Title	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab
Description	AUC is a measure of the serum concentration of the drug over time. AUC (0 - ∞) is area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). Participants who received bapineuzumab were reported.
Time Frame	0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6
Mean (Standard Deviation) [mcg*hour/mL]	1279 (266)	4323 (456)	7884 (640)	15405 (8438)

14. Secondary Outcome

Title	Systemic Clearance (CL) of Bapineuzumab
Description	CL is a quantitative measure of the rate at which a drug substance is removed from the body. Participants who received bapineuzumab were reported.
Time Frame	0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6
Mean (Standard Deviation) [mL/hour]	6.88 (1.32)	7.49 (1.71)	7.23 (1.49)	8.84 (3.97)

15. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) of Bapineuzumab
Description	Volume of distribution is defined as the theoretical blood volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Participants who received bapineuzumab were reported.
Time Frame	0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6
Mean (Standard Deviation) [mL]	5574 (906.5)	5947 (1406)	5827 (1611)	6879 (3132)

16. Secondary Outcome

Title	Mean Residence Time of Bapineuzumab
Description	MRT is average time for which the drug molecules resides in the body, after administration. It is calculated as area under the serum concentration versus time first moment curve from time zero (pre-dose) to extrapolated infinite time (AUMC [0 - ∞]) divided by area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (AUC[0 - ∞]). AUMC (0-∞) is calculated as AUMC(0-inf)= AUMCt + [(t x Ct) / kel] + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method, Ct is the concentration at time t and kel is the terminal phase rate constant. Participants who received bapineuzumab were reported.
Time Frame	0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6
Mean (Standard Deviation) [days]	34.5 (7.0)	33.3 (4.4)	33.4 (5.2)	32.4 (4.6)

17. Secondary Outcome

Title	Serum Decay Half-Life (t1/2) of Bapineuzumab
Description	Serum decay half-life is the time measured for the serum concentration to decrease by one half. Participants who received bapineuzumab were reported.
Time Frame	0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6 hours post start of infusion on Day 1; Day 2, 3; Week 1, 2, 4, 6, 8, 11, 13, 16, 26, 52

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6
Mean (Standard Deviation) [days]	28.1 (5.9)	26.7 (1.8)	26.2 (3.4)	15.0 (9.9)

18. Secondary Outcome

Title	Serum Bapineuzumab Concentrations
Description	Serum bapineuzumab concentration was determined by using a validated enzyme-linked immunosorbent assay (ELISA) method. Participants who received bapineuzumab were reported.
Time Frame	0 (pre-infusion), 0.5, 1, 1.5, 2, 4, 6, 24, 48, 168, 336, 672, 1008, 1344, 1848, 2184, 2688, 4368, 8736 hours post start of infusion

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration. Here 'n' signifies those participants who were evaluable for this measure at the specified time point for each arm, respectively.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6
0 Hour (n=0,0,0,0)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
0.5 Hour (n=6,5,6,6)	1602 (464)	5211 (1025)	8158 (332)	29206 (26241)
1 Hour (n=6,6,6,6)	2970 (624)	10259 (1421)	19939 (868)	48995 (41719)
1.5 Hour (n=6,6,6,6)	3093 (696)	10861 (1398)	20423 (1559)	43798 (34612)
2 Hour (n=6,6,6,6)	2854 (726)	10362 (1473)	19200 (1333)	48008 (26387)
4 Hour (n=6,6,6,6)	2917 (1079)	10044 (1564)	17588 (1762)	32399 (14264)
6 Hour (n=6,6,6,6)	2678 (845)	9753 (1209)	18935 (1194)	34349 (14934)
24 Hour (n=6,6,6,6)	2276 (665)	7774 (1249)	12983 (224)	25567 (20599)
48 Hour (n=6,6,6,6)	1946 (379)	6423 (774)	12179 (372)	20575 (18648)
168 Hour (n=6,6,6,6)	1279 (225)	4431 (826)	8170 (369)	15925 (10963)
336 Hour (n=6,6,6,6)	911 (271)	3441 (344)	6374 (547)	12325 (5331)
672 Hour (n=6,6,6,6)	599 (80)	1940 (328)	3379 (1409)	6720 (4830)
1008 Hour (n=6,6,6,6)	384 (127)	1396 (326)	2295 (376)	5064 (2197)
1344 Hour (n=6,6,6,6)	267 (76)	811 (120)	1389 (318)	4440 (1755)
1848 Hour (n=6,6,6,6)	158 (61)	519 (126)	990 (312)	2172 (1289)
2184 Hour (n=6,6,4,6)	107 (49)	375 (95)	796 (126)	1386 (950)
2688 Hour (n=6,6,6,6)	69 (41)	221 (96)	468 (101)	595 (678)
4368 Hour (n=5,5,6,2)	14 (12)	46 (20)	70 (28)	25 (10)
8736 Hour (n=0,0,0,0)	NA (NA)	NA (NA)	NA (NA)	NA (NA)

19. Secondary Outcome

Title	Number of Participants With Positive Serum Anti-Bapineuzumab Antibody
Description	Serum anti-bapineuzumab antibody concentration was determined by using a validated ELISA method.
Time Frame	Baseline (Day 1) up to Week 52

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	8
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%

20. Secondary Outcome

Title	Plasma Amyloid-beta (x-40) Concentrations
Description	Amyloid-beta (A-beta) is a peptide fragment of the amyloid precursor protein which is one of the characteristic hallmarks of Alzheimer's disease (AD). Total plasma amyloid-beta (x-40) was determined using a validated ELISA method.
Time Frame	0 (pre-infusion), 1, 6, 24, 336, 1008, 2184, 2688, 4368, 8736 hours post start of infusion

Outcome Measure Data

Analysis Population Description

PK data set included all randomized participants who had at least 1 available data of serum bapineuzumab, serum anti-bapineuzumab antibody or plasma amyloid beta concentration. Here 'n' signifies those participants who were evaluable for this measure at the specified time point for each arm, respectively.

Arm/Group Title	Bapineuzumab 0.15 mg/kg	Bapineuzumab 0.5 mg/kg	Bapineuzumab 1.0 mg/kg	Bapineuzumab 2.0 mg/kg	Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.	Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
Measure Participants	6	6	6	6	8
0 Hour (n=6,6,6,6,8)	309 (116)	298 (91)	276 (43)	339 (20)	281 (38)
1 Hour (n=6,5,5,6,8)	1009 (369)	1050 (142)	1593 (88)	1708 (247)	292 (48)
6 Hour (n=6,6,6,6,8)	1697 (871)	2664 (509)	3755 (356)	3905 (656)	293 (40)
24 Hour (n=6,6,6,6,8)	1474 (844)	3581 (660)	5333 (426)	7405 (1630)	302 (71)
336 Hour (n=6,6,6,6,8)	784 (320)	1675 (396)	3345 (485)	4325 (670)	279 (54)
1008 Hour (n=6,6,6,6,8)	543 (219)	985 (328)	1566 (281)	2664 (601)	287 (41)
2184 Hour (n=6,6,6,6,7)	331 (119)	488 (142)	668 (157)	1149 (432)	278 (59)
2688 Hour (n=6,6,6,6,7)	341 (108)	471 (114)	528 (128)	803 (268)	307 (81)
4368 Hour (n=5,6,6,6,7)	302 (86)	310 (74)	351 (33)	425 (68)	291 (71)
8736 Hour (n=5,6,6,6,7)	298 (107)	308 (29)	342 (41)	299 (22)	283 (42)

Adverse Events

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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Bapineuzumab 0.15 mg/kg		Bapineuzumab 0.5 mg/kg		Bapineuzumab 1.0 mg/kg		Bapineuzumab 2.0 mg/kg		Placebo
Arm/Group Description	Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1.		Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1.		Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1.		Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1.		Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1.
All Cause Mortality
	Bapineuzumab 0.15 mg/kg		Bapineuzumab 0.5 mg/kg		Bapineuzumab 1.0 mg/kg		Bapineuzumab 2.0 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Bapineuzumab 0.15 mg/kg		Bapineuzumab 0.5 mg/kg		Bapineuzumab 1.0 mg/kg		Bapineuzumab 2.0 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Bapineuzumab 0.15 mg/kg		Bapineuzumab 0.5 mg/kg		Bapineuzumab 1.0 mg/kg		Bapineuzumab 2.0 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		3/6 (50%)		6/6 (100%)		3/6 (50%)		7/8 (87.5%)
Cardiac disorders
Angina pectoris	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Ear and labyrinth disorders
Vertigo	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/8 (0%)
Eye disorders
Cataract	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/8 (12.5%)
Glaucoma	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)
Gastrointestinal disorders
Abdominal pain	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)
Abdominal pain upper	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)
Colonic polyp	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Haemorrhoids	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Periodontitis	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
General disorders
Injection site haemorrhage	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Infections and infestations
Abscess limb	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Cystitis	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Gastroenteritis	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)
Herpangina	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Nasopharyngitis	1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		2/8 (25%)
Oral herpes	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Pneumonia	0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)
Tinea infection	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/8 (0%)
Injury, poisoning and procedural complications
Spinal compression fracture	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Investigations
Aspartate aminotransferase increased	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Blood alkaline phosphatase increased	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Blood pressure increased	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)
Back pain	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Muscle rigidity	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Muscle twitching	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/8 (12.5%)
Musculoskeletal stiffness	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)
Nervous system disorders
Nystagmus	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Parkinsonism	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Psychiatric disorders
Delirium	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Insomnia	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/8 (0%)
Renal and urinary disorders
Dysuria	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Nocturia	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/8 (0%)
Upper respiratory tract inflammation	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/8 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)
Eczema	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)

Limitations/Caveats

[Not Specified]

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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.