Alzheimer Disease
Conditions
Brief summary
Evaluate safety, tolerability, and pharmacokinetics of single doses of the investigational AAB-001 Vaccine in Japanese patients with Alzheimer's disease.
Interventions
DRUGbapineuzumab
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.
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bapineuzumab 0.15 mg/kg Single dose of bapineuzumab (AAB-001) 0.15 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1. | 6 |
| Bapineuzumab 0.5 mg/kg Single dose of bapineuzumab 0.5 mg/kg intravenous infusion over 1 hour on Day 1. | 6 |
| Bapineuzumab 1.0 mg/kg Single dose of bapineuzumab 1.0 mg/kg intravenous infusion over 1 hour on Day 1. | 6 |
| Bapineuzumab 2.0 mg/kg Single dose of bapineuzumab 2.0 mg/kg intravenous infusion over 1 hour on Day 1. | 6 |
| Placebo Single dose of placebo matched to bapineuzumab intravenous infusion over 1 hour on Day 1. | 8 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Bapineuzumab 0.15 mg/kg | Bapineuzumab 0.5 mg/kg | Bapineuzumab 1.0 mg/kg | Bapineuzumab 2.0 mg/kg | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 60.67 years STANDARD_DEVIATION 5.16 | 72.17 years STANDARD_DEVIATION 8.38 | 72.17 years STANDARD_DEVIATION 10.87 | 64.83 years STANDARD_DEVIATION 5.19 | 68.75 years STANDARD_DEVIATION 8.89 | 67.78 years STANDARD_DEVIATION 8.72 |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 3 Participants | 3 Participants | 4 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 3 / 6 | 6 / 6 | 3 / 6 | 7 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Change From Baseline in Mini-Mental State Examination (MMSE) Score at 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.
Time frame: Baseline, Week 16
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 16 | 0.2 units on a scale | Standard Deviation 2.9 |
| Bapineuzumab 0.5 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 16 | -0.7 units on a scale | Standard Deviation 4.1 |
| Bapineuzumab 1.0 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 16 | 0.7 units on a scale | Standard Deviation 2.4 |
| Bapineuzumab 2.0 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 16 | -0.3 units on a scale | Standard Deviation 2.4 |
| Placebo | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 16 | -1.4 units on a scale | Standard Deviation 2.6 |
Primary
Change From Baseline in Mini-Mental State Examination (MMSE) Score at 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.
Time frame: Baseline, Week 52
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 52 | -2.4 units on a scale | Standard Deviation 1.9 |
| Bapineuzumab 0.5 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 52 | -3.8 units on a scale | Standard Deviation 6.4 |
| Bapineuzumab 1.0 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 52 | -0.7 units on a scale | Standard Deviation 2.7 |
| Bapineuzumab 2.0 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 52 | -1.2 units on a scale | Standard Deviation 5.6 |
| Placebo | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 52 | -2.9 units on a scale | Standard Deviation 1.3 |
Primary
Change From Baseline in Mini-Mental State Examination (MMSE) Score at 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.
Time frame: Baseline, Week 6
Population: Safety data set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Baseline | 16.8 units on a scale | Standard Deviation 2.9 |
| Bapineuzumab 0.15 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Change at Week 6 | -0.2 units on a scale | Standard Deviation 2.1 |
| Bapineuzumab 0.5 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Baseline | 21.0 units on a scale | Standard Deviation 3.6 |
| Bapineuzumab 0.5 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Change at Week 6 | 0.0 units on a scale | Standard Deviation 2.3 |
| Bapineuzumab 1.0 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Baseline | 21.0 units on a scale | Standard Deviation 4.6 |
| Bapineuzumab 1.0 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Change at Week 6 | -0.3 units on a scale | Standard Deviation 3 |
| Bapineuzumab 2.0 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Change at Week 6 | -0.2 units on a scale | Standard Deviation 3.8 |
| Bapineuzumab 2.0 mg/kg | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Baseline | 20.2 units on a scale | Standard Deviation 2.8 |
| Placebo | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Baseline | 20.6 units on a scale | Standard Deviation 3 |
| Placebo | Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 6 | Change at Week 6 | -1.9 units on a scale | Standard Deviation 3.1 |
Primary
Number of Participants With Clinically Significant Changes in Neurological Examinations
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
Population: Safety data set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bapineuzumab 0.15 mg/kg | Number of Participants With Clinically Significant Changes in Neurological Examinations | 0 participants |
| Bapineuzumab 0.5 mg/kg | Number of Participants With Clinically Significant Changes in Neurological Examinations | 0 participants |
| Bapineuzumab 1.0 mg/kg | Number of Participants With Clinically Significant Changes in Neurological Examinations | 0 participants |
| Bapineuzumab 2.0 mg/kg | Number of Participants With Clinically Significant Changes in Neurological Examinations | 0 participants |
| Placebo | Number of Participants With Clinically Significant Changes in Neurological Examinations | 0 participants |
Primary
Number of Participants With Clinically Significant Changes in Physical Examinations
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
Population: Safety data set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bapineuzumab 0.15 mg/kg | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 participants |
| Bapineuzumab 0.5 mg/kg | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 participants |
| Bapineuzumab 1.0 mg/kg | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 participants |
| Bapineuzumab 2.0 mg/kg | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 participants |
| Placebo | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 participants |
Primary
Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance
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
Population: Safety data set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bapineuzumab 0.15 mg/kg | Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance | 0 participants |
| Bapineuzumab 0.5 mg/kg | Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance | 0 participants |
| Bapineuzumab 1.0 mg/kg | Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance | 0 participants |
| Bapineuzumab 2.0 mg/kg | Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance | 1 participants |
Primary
Number of Participants With Laboratory Test Results of Potential Clinical Importance
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
Population: Safety data set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bapineuzumab 0.15 mg/kg | Number of Participants With Laboratory Test Results of Potential Clinical Importance | 6 participants |
| Bapineuzumab 0.5 mg/kg | Number of Participants With Laboratory Test Results of Potential Clinical Importance | 4 participants |
| Bapineuzumab 1.0 mg/kg | Number of Participants With Laboratory Test Results of Potential Clinical Importance | 3 participants |
| Bapineuzumab 2.0 mg/kg | Number of Participants With Laboratory Test Results of Potential Clinical Importance | 5 participants |
| Placebo | Number of Participants With Laboratory Test Results of Potential Clinical Importance | 5 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
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
Population: Safety data set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 5 participants |
| Bapineuzumab 0.15 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Bapineuzumab 0.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 3 participants |
| Bapineuzumab 0.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Bapineuzumab 1.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 6 participants |
| Bapineuzumab 1.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Bapineuzumab 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Bapineuzumab 2.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 3 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 7 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
Primary
Number of Participants With Vital Signs of Potential Clinical Importance
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
Population: Safety data set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bapineuzumab 0.15 mg/kg | Number of Participants With Vital Signs of Potential Clinical Importance | 2 participants |
| Bapineuzumab 0.5 mg/kg | Number of Participants With Vital Signs of Potential Clinical Importance | 0 participants |
| Bapineuzumab 1.0 mg/kg | Number of Participants With Vital Signs of Potential Clinical Importance | 2 participants |
| Bapineuzumab 2.0 mg/kg | Number of Participants With Vital Signs of Potential Clinical Importance | 1 participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Importance | 1 participants |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab | 1279 mcg*hour/mL | Standard Deviation 266 |
| Bapineuzumab 0.5 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab | 4323 mcg*hour/mL | Standard Deviation 456 |
| Bapineuzumab 1.0 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab | 7884 mcg*hour/mL | Standard Deviation 640 |
| Bapineuzumab 2.0 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Bapineuzumab | 15405 mcg*hour/mL | Standard Deviation 8438 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Bapineuzumab
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Bapineuzumab | 1260 mcg*hour/mL | Standard Deviation 254 |
| Bapineuzumab 0.5 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Bapineuzumab | 4264 mcg*hour/mL | Standard Deviation 462 |
| Bapineuzumab 1.0 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Bapineuzumab | 7818 mcg*hour/mL | Standard Deviation 652 |
| Bapineuzumab 2.0 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Bapineuzumab | 15313 mcg*hour/mL | Standard Deviation 8478 |
Secondary
Maximum Observed Serum Concentration (Cmax) of Bapineuzumab
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Maximum Observed Serum Concentration (Cmax) of Bapineuzumab | 3.32 microgram per milliliter (mcg/mL) | Standard Deviation 0.857 |
| Bapineuzumab 0.5 mg/kg | Maximum Observed Serum Concentration (Cmax) of Bapineuzumab | 11.1 microgram per milliliter (mcg/mL) | Standard Deviation 1.16 |
| Bapineuzumab 1.0 mg/kg | Maximum Observed Serum Concentration (Cmax) of Bapineuzumab | 21.0 microgram per milliliter (mcg/mL) | Standard Deviation 0.968 |
| Bapineuzumab 2.0 mg/kg | Maximum Observed Serum Concentration (Cmax) of Bapineuzumab | 61.0 microgram per milliliter (mcg/mL) | Standard Deviation 32.8 |
Secondary
Mean Residence Time of Bapineuzumab
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Mean Residence Time of Bapineuzumab | 34.5 days | Standard Deviation 7 |
| Bapineuzumab 0.5 mg/kg | Mean Residence Time of Bapineuzumab | 33.3 days | Standard Deviation 4.4 |
| Bapineuzumab 1.0 mg/kg | Mean Residence Time of Bapineuzumab | 33.4 days | Standard Deviation 5.2 |
| Bapineuzumab 2.0 mg/kg | Mean Residence Time of Bapineuzumab | 32.4 days | Standard Deviation 4.6 |
Secondary
Number of Participants With Positive Serum Anti-Bapineuzumab Antibody
Serum anti-bapineuzumab antibody concentration was determined by using a validated ELISA method.
Time frame: Baseline (Day 1) up to Week 52
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Bapineuzumab 0.15 mg/kg | Number of Participants With Positive Serum Anti-Bapineuzumab Antibody | 0 participants |
| Bapineuzumab 0.5 mg/kg | Number of Participants With Positive Serum Anti-Bapineuzumab Antibody | 0 participants |
| Bapineuzumab 1.0 mg/kg | Number of Participants With Positive Serum Anti-Bapineuzumab Antibody | 0 participants |
| Bapineuzumab 2.0 mg/kg | Number of Participants With Positive Serum Anti-Bapineuzumab Antibody | 0 participants |
| Placebo | Number of Participants With Positive Serum Anti-Bapineuzumab Antibody | 0 participants |
Secondary
Plasma Amyloid-beta (x-40) Concentrations
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 6 Hour (n=6,6,6,6,8) | 1697 picogram per milliliter (pg/mL) | Standard Deviation 871 |
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 8736 Hour (n=5,6,6,6,7) | 298 picogram per milliliter (pg/mL) | Standard Deviation 107 |
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 24 Hour (n=6,6,6,6,8) | 1474 picogram per milliliter (pg/mL) | Standard Deviation 844 |
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 4368 Hour (n=5,6,6,6,7) | 302 picogram per milliliter (pg/mL) | Standard Deviation 86 |
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 2688 Hour (n=6,6,6,6,7) | 341 picogram per milliliter (pg/mL) | Standard Deviation 108 |
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 1 Hour (n=6,5,5,6,8) | 1009 picogram per milliliter (pg/mL) | Standard Deviation 369 |
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 0 Hour (n=6,6,6,6,8) | 309 picogram per milliliter (pg/mL) | Standard Deviation 116 |
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 2184 Hour (n=6,6,6,6,7) | 331 picogram per milliliter (pg/mL) | Standard Deviation 119 |
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 1008 Hour (n=6,6,6,6,8) | 543 picogram per milliliter (pg/mL) | Standard Deviation 219 |
| Bapineuzumab 0.15 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 336 Hour (n=6,6,6,6,8) | 784 picogram per milliliter (pg/mL) | Standard Deviation 320 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 1 Hour (n=6,5,5,6,8) | 1050 picogram per milliliter (pg/mL) | Standard Deviation 142 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 0 Hour (n=6,6,6,6,8) | 298 picogram per milliliter (pg/mL) | Standard Deviation 91 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 6 Hour (n=6,6,6,6,8) | 2664 picogram per milliliter (pg/mL) | Standard Deviation 509 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 24 Hour (n=6,6,6,6,8) | 3581 picogram per milliliter (pg/mL) | Standard Deviation 660 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 336 Hour (n=6,6,6,6,8) | 1675 picogram per milliliter (pg/mL) | Standard Deviation 396 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 1008 Hour (n=6,6,6,6,8) | 985 picogram per milliliter (pg/mL) | Standard Deviation 328 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 2184 Hour (n=6,6,6,6,7) | 488 picogram per milliliter (pg/mL) | Standard Deviation 142 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 2688 Hour (n=6,6,6,6,7) | 471 picogram per milliliter (pg/mL) | Standard Deviation 114 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 4368 Hour (n=5,6,6,6,7) | 310 picogram per milliliter (pg/mL) | Standard Deviation 74 |
| Bapineuzumab 0.5 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 8736 Hour (n=5,6,6,6,7) | 308 picogram per milliliter (pg/mL) | Standard Deviation 29 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 1008 Hour (n=6,6,6,6,8) | 1566 picogram per milliliter (pg/mL) | Standard Deviation 281 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 4368 Hour (n=5,6,6,6,7) | 351 picogram per milliliter (pg/mL) | Standard Deviation 33 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 6 Hour (n=6,6,6,6,8) | 3755 picogram per milliliter (pg/mL) | Standard Deviation 356 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 24 Hour (n=6,6,6,6,8) | 5333 picogram per milliliter (pg/mL) | Standard Deviation 426 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 1 Hour (n=6,5,5,6,8) | 1593 picogram per milliliter (pg/mL) | Standard Deviation 88 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 336 Hour (n=6,6,6,6,8) | 3345 picogram per milliliter (pg/mL) | Standard Deviation 485 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 2184 Hour (n=6,6,6,6,7) | 668 picogram per milliliter (pg/mL) | Standard Deviation 157 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 0 Hour (n=6,6,6,6,8) | 276 picogram per milliliter (pg/mL) | Standard Deviation 43 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 8736 Hour (n=5,6,6,6,7) | 342 picogram per milliliter (pg/mL) | Standard Deviation 41 |
| Bapineuzumab 1.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 2688 Hour (n=6,6,6,6,7) | 528 picogram per milliliter (pg/mL) | Standard Deviation 128 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 1 Hour (n=6,5,5,6,8) | 1708 picogram per milliliter (pg/mL) | Standard Deviation 247 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 8736 Hour (n=5,6,6,6,7) | 299 picogram per milliliter (pg/mL) | Standard Deviation 22 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 0 Hour (n=6,6,6,6,8) | 339 picogram per milliliter (pg/mL) | Standard Deviation 20 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 6 Hour (n=6,6,6,6,8) | 3905 picogram per milliliter (pg/mL) | Standard Deviation 656 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 1008 Hour (n=6,6,6,6,8) | 2664 picogram per milliliter (pg/mL) | Standard Deviation 601 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 2688 Hour (n=6,6,6,6,7) | 803 picogram per milliliter (pg/mL) | Standard Deviation 268 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 4368 Hour (n=5,6,6,6,7) | 425 picogram per milliliter (pg/mL) | Standard Deviation 68 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 2184 Hour (n=6,6,6,6,7) | 1149 picogram per milliliter (pg/mL) | Standard Deviation 432 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 24 Hour (n=6,6,6,6,8) | 7405 picogram per milliliter (pg/mL) | Standard Deviation 1630 |
| Bapineuzumab 2.0 mg/kg | Plasma Amyloid-beta (x-40) Concentrations | 336 Hour (n=6,6,6,6,8) | 4325 picogram per milliliter (pg/mL) | Standard Deviation 670 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 24 Hour (n=6,6,6,6,8) | 302 picogram per milliliter (pg/mL) | Standard Deviation 71 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 4368 Hour (n=5,6,6,6,7) | 291 picogram per milliliter (pg/mL) | Standard Deviation 71 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 336 Hour (n=6,6,6,6,8) | 279 picogram per milliliter (pg/mL) | Standard Deviation 54 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 1008 Hour (n=6,6,6,6,8) | 287 picogram per milliliter (pg/mL) | Standard Deviation 41 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 8736 Hour (n=5,6,6,6,7) | 283 picogram per milliliter (pg/mL) | Standard Deviation 42 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 2184 Hour (n=6,6,6,6,7) | 278 picogram per milliliter (pg/mL) | Standard Deviation 59 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 0 Hour (n=6,6,6,6,8) | 281 picogram per milliliter (pg/mL) | Standard Deviation 38 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 2688 Hour (n=6,6,6,6,7) | 307 picogram per milliliter (pg/mL) | Standard Deviation 81 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 6 Hour (n=6,6,6,6,8) | 293 picogram per milliliter (pg/mL) | Standard Deviation 40 |
| Placebo | Plasma Amyloid-beta (x-40) Concentrations | 1 Hour (n=6,5,5,6,8) | 292 picogram per milliliter (pg/mL) | Standard Deviation 48 |
Secondary
Serum Bapineuzumab Concentrations
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 0 Hour (n=0,0,0,0) | NA nanogram per milliliter (ng/mL) | — |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 4 Hour (n=6,6,6,6) | 2917 nanogram per milliliter (ng/mL) | Standard Deviation 1079 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 1008 Hour (n=6,6,6,6) | 384 nanogram per milliliter (ng/mL) | Standard Deviation 127 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 672 Hour (n=6,6,6,6) | 599 nanogram per milliliter (ng/mL) | Standard Deviation 80 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 336 Hour (n=6,6,6,6) | 911 nanogram per milliliter (ng/mL) | Standard Deviation 271 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 6 Hour (n=6,6,6,6) | 2678 nanogram per milliliter (ng/mL) | Standard Deviation 845 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 1344 Hour (n=6,6,6,6) | 267 nanogram per milliliter (ng/mL) | Standard Deviation 76 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 8736 Hour (n=0,0,0,0) | NA nanogram per milliliter (ng/mL) | — |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 2688 Hour (n=6,6,6,6) | 69 nanogram per milliliter (ng/mL) | Standard Deviation 41 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 24 Hour (n=6,6,6,6) | 2276 nanogram per milliliter (ng/mL) | Standard Deviation 665 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 0.5 Hour (n=6,5,6,6) | 1602 nanogram per milliliter (ng/mL) | Standard Deviation 464 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 1 Hour (n=6,6,6,6) | 2970 nanogram per milliliter (ng/mL) | Standard Deviation 624 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 4368 Hour (n=5,5,6,2) | 14 nanogram per milliliter (ng/mL) | Standard Deviation 12 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 48 Hour (n=6,6,6,6) | 1946 nanogram per milliliter (ng/mL) | Standard Deviation 379 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 2 Hour (n=6,6,6,6) | 2854 nanogram per milliliter (ng/mL) | Standard Deviation 726 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 1.5 Hour (n=6,6,6,6) | 3093 nanogram per milliliter (ng/mL) | Standard Deviation 696 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 2184 Hour (n=6,6,4,6) | 107 nanogram per milliliter (ng/mL) | Standard Deviation 49 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 168 Hour (n=6,6,6,6) | 1279 nanogram per milliliter (ng/mL) | Standard Deviation 225 |
| Bapineuzumab 0.15 mg/kg | Serum Bapineuzumab Concentrations | 1848 Hour (n=6,6,6,6) | 158 nanogram per milliliter (ng/mL) | Standard Deviation 61 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 168 Hour (n=6,6,6,6) | 4431 nanogram per milliliter (ng/mL) | Standard Deviation 826 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 1848 Hour (n=6,6,6,6) | 519 nanogram per milliliter (ng/mL) | Standard Deviation 126 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 336 Hour (n=6,6,6,6) | 3441 nanogram per milliliter (ng/mL) | Standard Deviation 344 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 4368 Hour (n=5,5,6,2) | 46 nanogram per milliliter (ng/mL) | Standard Deviation 20 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 672 Hour (n=6,6,6,6) | 1940 nanogram per milliliter (ng/mL) | Standard Deviation 328 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 1344 Hour (n=6,6,6,6) | 811 nanogram per milliliter (ng/mL) | Standard Deviation 120 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 1008 Hour (n=6,6,6,6) | 1396 nanogram per milliliter (ng/mL) | Standard Deviation 326 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 1.5 Hour (n=6,6,6,6) | 10861 nanogram per milliliter (ng/mL) | Standard Deviation 1398 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 2 Hour (n=6,6,6,6) | 10362 nanogram per milliliter (ng/mL) | Standard Deviation 1473 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 0.5 Hour (n=6,5,6,6) | 5211 nanogram per milliliter (ng/mL) | Standard Deviation 1025 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 4 Hour (n=6,6,6,6) | 10044 nanogram per milliliter (ng/mL) | Standard Deviation 1564 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 0 Hour (n=0,0,0,0) | NA nanogram per milliliter (ng/mL) | — |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 2688 Hour (n=6,6,6,6) | 221 nanogram per milliliter (ng/mL) | Standard Deviation 96 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 6 Hour (n=6,6,6,6) | 9753 nanogram per milliliter (ng/mL) | Standard Deviation 1209 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 24 Hour (n=6,6,6,6) | 7774 nanogram per milliliter (ng/mL) | Standard Deviation 1249 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 2184 Hour (n=6,6,4,6) | 375 nanogram per milliliter (ng/mL) | Standard Deviation 95 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 48 Hour (n=6,6,6,6) | 6423 nanogram per milliliter (ng/mL) | Standard Deviation 774 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 1 Hour (n=6,6,6,6) | 10259 nanogram per milliliter (ng/mL) | Standard Deviation 1421 |
| Bapineuzumab 0.5 mg/kg | Serum Bapineuzumab Concentrations | 8736 Hour (n=0,0,0,0) | NA nanogram per milliliter (ng/mL) | — |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 2688 Hour (n=6,6,6,6) | 468 nanogram per milliliter (ng/mL) | Standard Deviation 101 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 0 Hour (n=0,0,0,0) | NA nanogram per milliliter (ng/mL) | — |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 0.5 Hour (n=6,5,6,6) | 8158 nanogram per milliliter (ng/mL) | Standard Deviation 332 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 1 Hour (n=6,6,6,6) | 19939 nanogram per milliliter (ng/mL) | Standard Deviation 868 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 1.5 Hour (n=6,6,6,6) | 20423 nanogram per milliliter (ng/mL) | Standard Deviation 1559 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 2 Hour (n=6,6,6,6) | 19200 nanogram per milliliter (ng/mL) | Standard Deviation 1333 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 4 Hour (n=6,6,6,6) | 17588 nanogram per milliliter (ng/mL) | Standard Deviation 1762 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 6 Hour (n=6,6,6,6) | 18935 nanogram per milliliter (ng/mL) | Standard Deviation 1194 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 24 Hour (n=6,6,6,6) | 12983 nanogram per milliliter (ng/mL) | Standard Deviation 224 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 48 Hour (n=6,6,6,6) | 12179 nanogram per milliliter (ng/mL) | Standard Deviation 372 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 168 Hour (n=6,6,6,6) | 8170 nanogram per milliliter (ng/mL) | Standard Deviation 369 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 336 Hour (n=6,6,6,6) | 6374 nanogram per milliliter (ng/mL) | Standard Deviation 547 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 672 Hour (n=6,6,6,6) | 3379 nanogram per milliliter (ng/mL) | Standard Deviation 1409 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 1008 Hour (n=6,6,6,6) | 2295 nanogram per milliliter (ng/mL) | Standard Deviation 376 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 1344 Hour (n=6,6,6,6) | 1389 nanogram per milliliter (ng/mL) | Standard Deviation 318 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 1848 Hour (n=6,6,6,6) | 990 nanogram per milliliter (ng/mL) | Standard Deviation 312 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 2184 Hour (n=6,6,4,6) | 796 nanogram per milliliter (ng/mL) | Standard Deviation 126 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 4368 Hour (n=5,5,6,2) | 70 nanogram per milliliter (ng/mL) | Standard Deviation 28 |
| Bapineuzumab 1.0 mg/kg | Serum Bapineuzumab Concentrations | 8736 Hour (n=0,0,0,0) | NA nanogram per milliliter (ng/mL) | — |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 168 Hour (n=6,6,6,6) | 15925 nanogram per milliliter (ng/mL) | Standard Deviation 10963 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 0.5 Hour (n=6,5,6,6) | 29206 nanogram per milliliter (ng/mL) | Standard Deviation 26241 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 1848 Hour (n=6,6,6,6) | 2172 nanogram per milliliter (ng/mL) | Standard Deviation 1289 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 48 Hour (n=6,6,6,6) | 20575 nanogram per milliliter (ng/mL) | Standard Deviation 18648 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 24 Hour (n=6,6,6,6) | 25567 nanogram per milliliter (ng/mL) | Standard Deviation 20599 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 0 Hour (n=0,0,0,0) | NA nanogram per milliliter (ng/mL) | — |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 2184 Hour (n=6,6,4,6) | 1386 nanogram per milliliter (ng/mL) | Standard Deviation 950 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 6 Hour (n=6,6,6,6) | 34349 nanogram per milliliter (ng/mL) | Standard Deviation 14934 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 4 Hour (n=6,6,6,6) | 32399 nanogram per milliliter (ng/mL) | Standard Deviation 14264 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 2 Hour (n=6,6,6,6) | 48008 nanogram per milliliter (ng/mL) | Standard Deviation 26387 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 2688 Hour (n=6,6,6,6) | 595 nanogram per milliliter (ng/mL) | Standard Deviation 678 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 1.5 Hour (n=6,6,6,6) | 43798 nanogram per milliliter (ng/mL) | Standard Deviation 34612 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 1 Hour (n=6,6,6,6) | 48995 nanogram per milliliter (ng/mL) | Standard Deviation 41719 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 8736 Hour (n=0,0,0,0) | NA nanogram per milliliter (ng/mL) | — |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 1008 Hour (n=6,6,6,6) | 5064 nanogram per milliliter (ng/mL) | Standard Deviation 2197 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 672 Hour (n=6,6,6,6) | 6720 nanogram per milliliter (ng/mL) | Standard Deviation 4830 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 4368 Hour (n=5,5,6,2) | 25 nanogram per milliliter (ng/mL) | Standard Deviation 10 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 1344 Hour (n=6,6,6,6) | 4440 nanogram per milliliter (ng/mL) | Standard Deviation 1755 |
| Bapineuzumab 2.0 mg/kg | Serum Bapineuzumab Concentrations | 336 Hour (n=6,6,6,6) | 12325 nanogram per milliliter (ng/mL) | Standard Deviation 5331 |
Secondary
Serum Decay Half-Life (t1/2) of Bapineuzumab
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Serum Decay Half-Life (t1/2) of Bapineuzumab | 28.1 days | Standard Deviation 5.9 |
| Bapineuzumab 0.5 mg/kg | Serum Decay Half-Life (t1/2) of Bapineuzumab | 26.7 days | Standard Deviation 1.8 |
| Bapineuzumab 1.0 mg/kg | Serum Decay Half-Life (t1/2) of Bapineuzumab | 26.2 days | Standard Deviation 3.4 |
| Bapineuzumab 2.0 mg/kg | Serum Decay Half-Life (t1/2) of Bapineuzumab | 15.0 days | Standard Deviation 9.9 |
Secondary
Systemic Clearance (CL) of Bapineuzumab
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Systemic Clearance (CL) of Bapineuzumab | 6.88 mL/hour | Standard Deviation 1.32 |
| Bapineuzumab 0.5 mg/kg | Systemic Clearance (CL) of Bapineuzumab | 7.49 mL/hour | Standard Deviation 1.71 |
| Bapineuzumab 1.0 mg/kg | Systemic Clearance (CL) of Bapineuzumab | 7.23 mL/hour | Standard Deviation 1.49 |
| Bapineuzumab 2.0 mg/kg | Systemic Clearance (CL) of Bapineuzumab | 8.84 mL/hour | Standard Deviation 3.97 |
Secondary
Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Bapineuzumab 0.15 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab | 1.51 hours |
| Bapineuzumab 0.5 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab | 1.54 hours |
| Bapineuzumab 1.0 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab | 1.53 hours |
| Bapineuzumab 2.0 mg/kg | Time to Reach Maximum Observed Serum Concentration (Tmax) of Bapineuzumab | 1.71 hours |
Secondary
Volume of Distribution at Steady State (Vss) of Bapineuzumab
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bapineuzumab 0.15 mg/kg | Volume of Distribution at Steady State (Vss) of Bapineuzumab | 5574 mL | Standard Deviation 906.5 |
| Bapineuzumab 0.5 mg/kg | Volume of Distribution at Steady State (Vss) of Bapineuzumab | 5947 mL | Standard Deviation 1406 |
| Bapineuzumab 1.0 mg/kg | Volume of Distribution at Steady State (Vss) of Bapineuzumab | 5827 mL | Standard Deviation 1611 |
| Bapineuzumab 2.0 mg/kg | Volume of Distribution at Steady State (Vss) of Bapineuzumab | 6879 mL | Standard Deviation 3132 |