Multiple IV Dose Study Of PF-04360365 In Patients With Mild To Moderate Alzheimer's Disease

Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Baseline

ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's Disease. It comprised of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). ADAS-cog total score was calculated as the sum of scores for the 11 items and ranged from 0 to 70. Higher total and individual item scores indicate greater cognitive impairment. Baseline was defined as the last assessment prior to the first study drug infusion.

Time frame: Baseline

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Month 19

ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's Disease. It comprised of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). ADAS-cog total score was calculated as the sum of scores for the 11 items and ranged from 0 to 70. Higher total and individual item scores indicate greater cognitive impairment. Baseline was defined as the last assessment prior to the first study drug infusion.

Time frame: Baseline and Month 19

Disability Assessment for Dementia (DAD) Score at Baseline

DAD is a functional assessment based on interview with the caregiver. It consisted of 40 items, 17 related to self-care and 23 items involving instrumental activities of daily living. Each item was scored as yes = 1, no = 0 and not applicable= N/A. A total score was obtained by adding the rating for each question and converting this to a total score out of 100. The items rated N/A were not considered for the total score. DAD total score ranged from 0 to 100, with higher scores indicating better functioning. Baseline was defined as the last assessment prior to the first study drug infusion.

Time frame: Baseline

Change From Baseline in Disability Assessment for Dementia (DAD) Score at Month 19

DAD is a functional assessment based on interview with the caregiver. It consisted of 40 items, 17 related to self-care and 23 items involving instrumental activities of daily living. Each item was scored as yes = 1, no = 0 and not applicable= N/A. A total score was obtained by adding the rating for each question and converting this to a total score out of 100. The items rated N/A were not considered for the total score. DAD total score ranged from 0 to 100, with higher scores indicating better functioning. Baseline was defined as the last assessment prior to the first study drug infusion.

Time frame: Baseline and Month 19

Mean Plasma Concentration of Amyloid Beta 1-x (Aβ1-x)

Time frame: 0 Hour (pre-dose) and 2 hours on Day 1, 60, 120, 180, 240, 300, 360, 420, 480, 540; Day 90, 150, 210, 390, 570, 660, 720

Mean Plasma Concentration of Amyloid Beta 1-40 (Aβ1-40)

Time frame: 0 Hour (pre-dose) and 2 hours on Day 1, 60, 120, 180, 240, 300, 360, 420, 480, 540; Day 90, 150, 210, 390, 570, 660, 720

Mean Plasma Concentration of Amyloid Beta 1-42 (Aβ1-42)

Results are not reported for PF-04360365 0.1, 0.5, 1.0 mg/kg, Placebo (Part A and B) arms because plasma Aβ1-42 concentrations were sporadic and below the lower limit of quantification (20 pg/mL).

Time frame: 0 Hour (pre-dose) and 2 hours on Day 1, 60, 120, 180, 240, 300, 360, 420, 480, 540; Day 90, 150, 210, 390, 570, 660, 720

Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (Aβ1-x)

Time frame: Day 0 (Hour 0), 90, 570

Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-40 (Aβ1-40)

Time frame: Day 0 (Hour 0), 90, 570

Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-42 (Aβ1-42)

Time frame: Day 0 (Hour 0), 90, 570

Mean Cerebrospinal Fluid (CSF) Concentration of Total Tau and Phospho-tau (P-tau)

Time frame: Day 0 (Hour 0), 90, 570

Number of Participants With Abnormal Cerebrospinal Fluid (CSF) Protein, Red Blood Cells (RBCs), White Blood Cells (WBCs), and Glucose Concentration

Abnormality was defined as concentration either less than lower limit of normal (LLN) or more than upper limit of normal (ULN). Baseline was defined as the last assessment prior to the first study drug infusion

Time frame: Baseline up to Month 24

Number of Participants With Serum Anti-Drug Anti Body (ADA)

Serum samples were analyzed for the presence or absence of anti-PF-04360365 antibodies using validated semi-quantitative enzyme linked immunosorbent assay (ELISA). Only participants receiving PF-04360365 were analyzed for this outcome measure.

Time frame: Day 1 up to Month 24